PSCBS/0000755000176200001440000000000015000525222011115 5ustar liggesusersPSCBS/tests/0000755000176200001440000000000015000465060012262 5ustar liggesusersPSCBS/tests/segmentByCBS,report.R0000644000176200001440000000247714564051545016231 0ustar liggesusers# This test script calls a report generator which requires # the 'ggplot2' package, which in turn will require packages # 'colorspace', 'dichromat', 'munsell', 'reshape2' and 'scales'. # Only run this test in full testing mode if (Sys.getenv("_R_CHECK_FULL_") != "") { library("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) data <- data.frame(chromosome=data$chromosome, x=data$x, y=data$CT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # CBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=5),] str(dataS) gaps <- findLargeGaps(dataS, minLength=2e6) knownSegments <- gapsToSegments(gaps) # CBS segmentation fit <- segmentByCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) signalType(fit) <- "ratio" # Fake a multi-chromosome segmentation fit1 <- fit fit2 <- renameChromosomes(fit, from=1, to=2) fit <- c(fit1, fit2) report(fit, sampleName="CBS", studyName="CBS-Ex", verbose=-10) } # if (Sys.getenv("_R_CHECK_FULL_")) PSCBS/tests/segmentByPairedPSCBS,seqOfSegmentsByDP.R0000644000176200001440000000341014564051545021574 0ustar liggesuserslibrary("PSCBS") subplots <- R.utils::subplots stext <- R.utils::stext # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Run light-weight tests by default if (Sys.getenv("_R_CHECK_FULL_") == "") { # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 3L # Number of bootstrap samples (see below) B <- 100L } else { # Full tests nSegs <- 12L B <- 1000L } str(dataS) R.oo::attachLocally(dataS) gaps <- findLargeGaps(dataS, minLength=2e6) knownSegments <- gapsToSegments(gaps, dropGaps=TRUE) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) print(fit) fit1 <- fit fit2 <- renameChromosomes(fit1, from=1, to=2) fit <- c(fit1, fit2) knownSegments <- tileChromosomes(fit)$params$knownSegments segList <- seqOfSegmentsByDP(fit, verbose=-10) K <- length(segList) ks <- seq(from=1, to=K, length.out=min(5,K)) subplots(length(ks), ncol=1, byrow=TRUE) par(mar=c(2,1,1,1)) for (kk in ks) { knownSegmentsKK <- segList[[kk]] fitKK <- resegment(fit, knownSegments=knownSegmentsKK, undoTCN=+Inf, undoDH=+Inf) plotTracks(fitKK, tracks="tcn,c1,c2", Clim=c(0,5), add=TRUE) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) stext(side=3, pos=0, sprintf("Number of segments: %d", nrow(knownSegmentsKK))) } # for (kk ...) PSCBS/tests/randomSeed.R0000644000176200001440000001001514564051545014500 0ustar liggesuserslibrary("PSCBS") message("*** randomSeed() - setup ...") ovars <- ls(envir=globalenv()) genv <- globalenv() RNGkind("Mersenne-Twister") if (exists(".Random.seed", envir=genv, inherits=FALSE)) rm(list=".Random.seed", envir=genv, inherits=FALSE) seed0 <- genv$.Random.seed stopifnot(is.null(seed0)) okind0 <- RNGkind()[1L] sample1 <- function() { sample(0:9, size=1L) } message("*** randomSeed() - setup ... done") message("*** randomSeed('get') ...") ## Get random seed seed <- randomSeed("get") stopifnot(identical(seed, seed0)) ## Repeat after new sample y1 <- sample1() message(sprintf("Random number: %d", y1)) seed1 <- randomSeed("get") stopifnot(!identical(seed1, seed0)) message("*** randomSeed('get') ... done") message("*** randomSeed('set', 42L) ...") randomSeed("set", seed=42L) seed2 <- randomSeed("get") stopifnot(!identical(seed2, seed1)) y2 <- sample1() message(sprintf("Random number: %d (with random seed = 42L)", y2)) ## Reset to previous state randomSeed("reset") seed3 <- randomSeed("get") stopifnot(identical(seed3, seed1)) stopifnot(identical(RNGkind()[1L], okind0), identical(randomSeed("get"), seed1)) message("*** randomSeed('set', 42L) ... done") message("*** randomSeed('set', NULL) ...") randomSeed("set", seed=NULL) seed4 <- randomSeed("get") stopifnot(is.null(seed4)) y3 <- sample1() message(sprintf("Random number: %d", y3)) message("*** randomSeed('set', NULL) ... done") message("*** randomSeed('set', 42L) again ...") seed5 <- randomSeed("get") randomSeed("set", seed=42L) y4 <- sample1() message(sprintf("Random number: %d (with random seed = 42L)", y4)) stopifnot(identical(y4, y2)) randomSeed("reset") stopifnot(identical(RNGkind()[1L], okind0), identical(randomSeed("get"), seed5)) message("*** randomSeed('set', 42L) again ... done") ## L'Ecuyer-CMRG: Random number generation for parallel processing message("*** randomSeed(): L'Ecuyer-CMRG stream ...") okind <- RNGkind()[1L] stopifnot(identical(okind, okind0)) randomSeed("set", seed=NULL) oseed <- randomSeed("get") stopifnot(is.null(oseed)) randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") oseed2 <- randomSeed("reset") str(oseed2) stopifnot(identical(oseed2, oseed)) stopifnot(identical(RNGkind()[1L], okind), identical(randomSeed("get"), oseed)) randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") seed0 <- randomSeed("get") seeds0 <- lapply(1:10, FUN=function(i) randomSeed("advance")) oseed2 <- randomSeed("reset") stopifnot(identical(oseed2, oseed)) stopifnot(identical(RNGkind()[1L], okind), identical(randomSeed("get"), oseed)) ## Assert reproducible .Random.seed stream randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") seed1 <- randomSeed("get") seeds1 <- lapply(1:10, FUN=function(i) randomSeed("advance")) stopifnot(identical(seed1, seed0)) stopifnot(identical(seeds1, seeds0)) randomSeed("reset") stopifnot(identical(RNGkind()[1L], okind), identical(randomSeed("get"), oseed)) randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") seeds2 <- randomSeed("advance", n=10L) stopifnot(identical(seeds2, seeds0)) randomSeed("reset") stopifnot(identical(RNGkind()[1L], okind), identical(randomSeed("get"), oseed)) randomSeed("set", seed=seeds2[[1]], kind="L'Ecuyer-CMRG") randomSeed("reset") stopifnot(identical(RNGkind()[1L], okind), identical(randomSeed("get"), oseed)) randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") y0 <- sapply(1:10, FUN=function(ii) { randomSeed("advance") sample1() }) print(y0) randomSeed("reset") randomSeed("set", seed=42L, kind="L'Ecuyer-CMRG") y1 <- sapply(1:10, FUN=function(ii) { randomSeed("advance") sample1() }) print(y1) stopifnot(identical(y1, y0)) randomSeed("reset") stopifnot(identical(RNGkind()[1L], okind)) message("*** randomSeed(): L'Ecuyer-CMRG stream ... done") ## Cleanup message("*** randomSeed() - cleanup ...") genv <- globalenv() RNGkind("Mersenne-Twister") if (exists(".Random.seed", envir=genv, inherits=FALSE)) rm(list=".Random.seed", envir=genv, inherits=FALSE) rm(list=ovars, envir=globalenv()) message("*** randomSeed() - cleanup ... done") PSCBS/tests/segmentByCBS,shiftTCN.R0000644000176200001440000000550214564051545016370 0ustar liggesuserslibrary("PSCBS") subplots <- R.utils::subplots # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) idxs <- which(200 <= x & x < 300) y[idxs] <- y[idxs] + 1 idxs <- which(350 <= x & x < 400) y[idxs] <- NA # centromere x[idxs] <- NA # centromere idxs <- which(650 <= x & x < 800) y[idxs] <- y[idxs] - 1 x <- x*1e5 keep <- is.finite(x) x <- x[keep] y <- y[keep] data <- list() for (chr in 1:2) { data[[chr]] <- data.frame(chromosome=chr, y=y, x=x) } data <- Reduce(rbind, data) subplots(7, ncol=1) par(mar=c(1.7,1,0.2,1)+0.1) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(data) print(fit) Clim <- c(-3,3) + c(0,10) plotTracks(fit, Clim=Clim) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Shifting every other chromosome # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitList <- list() chrs <- getChromosomes(fit) for (kk in seq_along(chrs)) { chr <- chrs[kk] fitKK <- extractChromosome(fit, chr) if (kk %% 2 == 0) { fitKK <- shiftTCN(fitKK, shift=+10) } fitList[[kk]] <- fitKK } # for (kk ...) fitT <- do.call(c, fitList) # Sanity check stopifnot(nbrOfSegments(fitT) == nbrOfSegments(fit)) plotTracks(fitT, Clim=Clim) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Shifting every other known segment # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - gaps <- findLargeGaps(data, minLength=40e5) knownSegments <- gapsToSegments(gaps, dropGaps=TRUE) fit <- segmentByCBS(data, knownSegments=knownSegments) subplots(2, ncol=1) plotTracks(fit, Clim=Clim) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) fitList <- list() for (kk in seq_len(nrow(knownSegments))) { seg <- knownSegments[kk,] start <- seg$start end <- seg$end fitKK <- extractChromosome(fit, seg$chromosome) segsKK <- getSegments(fitKK) idxStart <- min(which(segsKK$start >= start)) idxEnd <- max(which(segsKK$end <= end)) idxs <- idxStart:idxEnd fitKK <- extractSegments(fitKK, idxs) if (kk %% 2 == 0) { fitKK <- shiftTCN(fitKK, shift=+10) } fitList[[kk]] <- fitKK } # for (kk ...) fitT <- do.call(c, fitList) # Sanity check stopifnot(nbrOfSegments(fitT) == nbrOfSegments(fit)) plotTracks(fitT, Clim=Clim) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) segList <- seqOfSegmentsByDP(fit) K <- length(segList) subplots(K, ncol=2, byrow=FALSE) par(mar=c(2,1,1,1)) for (kk in 1:K) { knownSegments <- segList[[kk]] fitKK <- resegment(fit, knownSegments=knownSegments, undo=+Inf) plotTracks(fitKK, Clim=c(-3,3)) } # for (kk ...) PSCBS/tests/findLargeGaps.R0000644000176200001440000000270614564051545015135 0ustar liggesuserslibrary("PSCBS") # Simulating copy-number data set.seed(0xBEEF) # Simulate CN data J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- seq(from=1, to=100e6, length.out=J) data <- data.frame(chromosome=0L, x=x) gaps <- findLargeGaps(x=x, minLength=1e6) print(gaps) stopifnot(is.data.frame(gaps)) stopifnot(nrow(gaps) == 0L) segs <- gapsToSegments(gaps) print(segs) stopifnot(is.data.frame(segs)) stopifnot(nrow(segs) == 1L) gaps <- findLargeGaps(data, minLength=1e6) print(gaps) stopifnot(is.data.frame(gaps)) stopifnot(nrow(gaps) == 0L) segs <- gapsToSegments(gaps) print(segs) stopifnot(is.data.frame(segs)) stopifnot(nrow(segs) == 1L) ## Add missing values data2 <- data data$x[30e6 < x & x < 50e6] <- NA gaps <- findLargeGaps(data, minLength=1e6) print(gaps) stopifnot(is.data.frame(gaps)) stopifnot(nrow(gaps) == 1L) segs <- gapsToSegments(gaps) print(segs) stopifnot(is.data.frame(segs)) stopifnot(nrow(segs) == 3L) # BUG FIX: Issue #6 gaps <- findLargeGaps(chromosome=rep(1,10), x=1:10, minLength=2) print(gaps) stopifnot(is.data.frame(gaps)) stopifnot(nrow(gaps) == 0L) # BUG FIX: Issue #9 segs <- gapsToSegments(gaps) print(segs) stopifnot(is.data.frame(segs)) stopifnot(nrow(segs) == 1L) # BUG FIX: PSCBS GitHub Issue #8 gaps <- try({ findLargeGaps(chromosome=rep(1,3), x=as.numeric(1:3), minLength=1) }) stopifnot(inherits(gaps, "try-error")) PSCBS/tests/segmentByPairedPSCBS.R0000644000176200001440000001013714564051545016301 0ustar liggesusers########################################################### # This tests: # - segmentByPairedPSCBS(...) # - segmentByPairedPSCBS(..., knownSegments) # - tileChromosomes() # - plotTracks() ########################################################### library("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Run light-weight tests by default if (Sys.getenv("_R_CHECK_FULL_") == "") { # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 4L } else { # Full tests nSegs <- 11L } str(dataS) fig <- 1 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (a) Don't segment the centromere (and force a separator) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome = c( 1, 1, 1), start = c( -Inf, NA, 141510003), end = c(120992603, NA, +Inf) ) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) print(fit) # Plot results dev.set(2L) plotTracks(fit) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Sanity check stopifnot(nbrOfSegments(fit) == nSegs) fit1 <- fit # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (b) Segment also the centromere (which will become NAs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome = c( 1, 1, 1), start = c( -Inf, 120992604, 141510003), end = c(120992603, 141510002, +Inf) ) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) print(fit) # Plot results dev.set(3L) plotTracks(fit) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Sanity check [TO FIX: See above] stopifnot(nbrOfSegments(fit) == nSegs) fit2 <- fit # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (c) Do not segment the centromere (without a separator) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome = c( 1, 1), start = c( -Inf, 141510003), end = c(120992603, +Inf) ) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) print(fit) # Plot results dev.set(4L) plotTracks(fit) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Sanity check stopifnot(nbrOfSegments(fit) == nSegs-1L) fit3 <- fit # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (d) Skip the identification of new change points # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome = c( 1, 1), start = c( -Inf, 141510003), end = c(120992603, +Inf) ) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, undoTCN=Inf, undoDH=Inf, seed=0xBEEF, verbose=-10) print(fit) # Plot results dev.set(5L) plotTracks(fit) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Sanity check stopifnot(nbrOfSegments(fit) == nrow(knownSegments)) fit4 <- fit # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tiling multiple chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulate multiple chromosomes fit1 <- fit fit2 <- renameChromosomes(fit, from=1, to=2) fitM <- c(fit1, fit2) # Tile chromosomes fitT <- tileChromosomes(fitM) fitTb <- tileChromosomes(fitT) stopifnot(identical(fitTb, fitT)) # Plotting multiple chromosomes plotTracks(fitT) PSCBS/tests/segmentByPairedPSCBS,DH.R0000644000176200001440000000374014564051545016573 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Run light-weight tests # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 3L # Number of bootstrap samples (see below) B <- 100L str(dataS) R.oo::attachLocally(dataS) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calculate DH # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - muN <- aroma.light::callNaiveGenotypes(betaN, censorAt=c(0,1)) # SNPs are identifies as those loci that have non-missing 'betaT' & 'muN' isSnp <- (!is.na(betaT) & !is.na(muN)) isHet <- isSnp & (muN == 1/2) rho <- rep(NA_real_, length=length(muN)) rho[isHet] <- 2*abs(betaT[isHet]-1/2) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation using TCN and DH only # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByPairedPSCBS(CT, rho=rho, chromosome=chromosome, x=x, seed=0xBEEF, verbose=-10) print(fit) # Plot results plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=B, verbose=-10) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance (AB) and # in loss-of-heterozygosity (LOH) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- callAB(fit, verbose=-10) fit <- callLOH(fit, verbose=-10) print(fit) plotTracks(fit) PSCBS/tests/segmentByCBS,futures.R0000644000176200001440000000401414564051545016400 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 ## Create multiple chromosomes data <- knownSegments <- list() for (cc in 1:3) { data[[cc]] <- data.frame(chromosome=cc, y=y, x=x) knownSegments[[cc]] <- data.frame( chromosome=c( cc, cc, cc), start =x[c( 1, 350, 401)], end =x[c(349, 400, J)] ) } data <- Reduce(rbind, data) str(data) knownSegments <- Reduce(rbind, knownSegments) str(knownSegments) message("*** segmentByCBS() via futures ...") message("*** segmentByCBS() via futures with 'future' attached ...") library("future") oplan <- plan() strategies <- c("sequential", "multisession") ## Test 'future.batchtools' futures? pkg <- "future.batchtools" if (require(pkg, character.only=TRUE)) { strategies <- c(strategies, "batchtools_local") } message("Future strategies to test: ", paste(sQuote(strategies), collapse=", ")) fits <- list() for (strategy in strategies) { message(sprintf("- segmentByCBS() using '%s' futures ...", strategy)) plan(strategy) fit <- segmentByCBS(data, seed=0xBEEF, verbose=TRUE) fits[[strategy]] <- fit stopifnot(all.equal(fit, fits[[1]])) } message("*** segmentByCBS() via futures with known segments ...") fits <- list() dataT <- subset(data, chromosome == 1) for (strategy in strategies) { message(sprintf("- segmentByCBS() w/ known segments using '%s' futures ...", strategy)) plan(strategy) fit <- segmentByCBS(dataT, knownSegments=knownSegments, seed=0xBEEF, verbose=TRUE) fits[[strategy]] <- fit stopifnot(all.equal(fit, fits[[1]])) } message("*** segmentByCBS() via futures ... DONE") ## Cleanup plan(oplan) rm(list=c("fits", "dataT", "data", "fit")) PSCBS/tests/segmentByPairedPSCBS,calls.R0000644000176200001440000000710314564051545017373 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Find centromere gaps <- findLargeGaps(dataS, minLength=2e6) knownSegments <- gapsToSegments(gaps) # Run light-weight tests by default if (Sys.getenv("_R_CHECK_FULL_") == "") { # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 4L # Number of bootstrap samples (see below) B <- 100L } else { # Full tests nSegs <- 11L B <- 1000L } str(dataS) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) print(fit) # Plot results plotTracks(fit) # Sanity check stopifnot(nbrOfSegments(fit) == nSegs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=B, verbose=-10) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments with run of homozygosity (ROH) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- callROH(fit, verbose=-10) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Estimate background # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - kappa <- estimateKappa(fit, verbose=-10) print(kappa) ## [1] 0.226011 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance (AB) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in DH for calling AB # (which be done by default by the caller, if skipped here) deltaAB <- estimateDeltaAB(fit, flavor="qq(DH)", verbose=-10) if (Sys.getenv("_R_CHECK_FULL_") == "") { # Ad hoc workaround for not utilizing all of the data # in the test, which results in a poor estimate deltaAB <- 0.165 } print(deltaAB) ## [1] 0.1657131 fit <- callAB(fit, delta=deltaAB, verbose=-10) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaAB == deltaAB) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in loss-of-heterozygosity (LOH) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in C1 for calling LOH # (which be done by default by the caller, if skipped here) deltaLOH <- estimateDeltaLOH(fit, flavor="minC1|nonAB", verbose=-10) print(deltaLOH) ## [1] 0.625175 fit <- callLOH(fit, delta=deltaLOH, verbose=-10) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaLOH == deltaLOH) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments that are gained, copy neutral, and lost # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- callGNL(fit, verbose=-10) print(fit) plotTracks(fit) PSCBS/tests/segmentByCBS,median.R0000644000176200001440000000707514564051545016152 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 x <- sort(runif(J, max=J)) * 1e5 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps outliers <- seq(from=1L, to=J, length.out=0.2*J) y[outliers] <- y[outliers] + 1.5 w <- rep(1.0, times=J) w[outliers] <- 0.01 data <- data.frame(chromosome=1L, x=x, y=y) dataW <- cbind(data, w=w) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Single-chromosome segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - par(mar=c(2,3,0.2,1)+0.1) # Segment without weights fit <- segmentByCBS(data) sampleName(fit) <- "CBS_Example" print(fit) plotTracks(fit) ## Highlight outliers (they pull up the mean levels) points(x[outliers]/1e6, y[outliers], col="purple") # Segment without weights but with median fitM <- segmentByCBS(data, avg="median") sampleName(fitM) <- "CBS_Example (median)" print(fitM) drawLevels(fitM, col="magenta", lty=3) # Segment with weights fitW <- segmentByCBS(dataW, avg="median") sampleName(fitW) <- "CBS_Example (weighted)" print(fitW) drawLevels(fitW, col="red") # Segment with weights and median fitWM <- segmentByCBS(dataW, avg="median") sampleName(fitWM) <- "CBS_Example (weighted median)" print(fitWM) drawLevels(fitWM, col="orange", lty=3) legend("topright", bg="white", legend=c("outliers", "non-weighted CBS (mean)", "non-weighted CBS (median)", "weighted CBS (mean)", "weighted CBS (median)"), col=c("purple", "purple", "magenta", "red", "orange"), lwd=c(NA,3,3,3,3), lty=c(NA,1,3,1,3), pch=c(1,NA,NA,NA,NA)) ## Assert that weighted segment means are less biased dmean <- getSegments(fit)$mean - getSegments(fitW)$mean cat("Segment mean differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) dmean <- getSegments(fitM)$mean - getSegments(fitWM)$mean cat("Segment median differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multi-chromosome segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data2 <- data data2$chromosome <- 2L data <- rbind(data, data2) dataW <- cbind(data, w=w) par(mar=c(2,3,0.2,1)+0.1) # Segment without weights fit <- segmentByCBS(data) sampleName(fit) <- "CBS_Example" print(fit) plotTracks(fit, Clim=c(-3,3)) # Segment without weights but with median fitM <- segmentByCBS(data, avg="median") sampleName(fitM) <- "CBS_Example (median)" print(fitM) drawLevels(fitM, col="magenta", lty=3) # Segment with weights fitW <- segmentByCBS(dataW, avg="median") sampleName(fitW) <- "CBS_Example (weighted)" print(fitW) drawLevels(fitW, col="red") # Segment with weights and median fitWM <- segmentByCBS(dataW, avg="median") sampleName(fitWM) <- "CBS_Example (weighted median)" print(fitWM) drawLevels(fitWM, col="orange", lty=3) legend("topright", bg="white", legend=c("outliers", "non-weighted CBS (mean)", "non-weighted CBS (median)", "weighted CBS (mean)", "weighted CBS (median)"), col=c("purple", "purple", "magenta", "red", "orange"), lwd=c(NA,3,3,3,3), lty=c(NA,1,3,1,3), pch=c(1,NA,NA,NA,NA)) ## Assert that weighted segment means are less biased dmean <- getSegments(fit)$mean - getSegments(fitW)$mean cat("Segment mean differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) dmean <- getSegments(fitM)$mean - getSegments(fitWM)$mean cat("Segment median differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) PSCBS/tests/segmentByPairedPSCBS,futures.R0000644000176200001440000000516214564051545017775 0ustar liggesuserslibrary(PSCBS) library(utils) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Run light-weight tests by default if (Sys.getenv("_R_CHECK_FULL_") == "") { # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 4L } else { # Full tests nSegs <- 11L } str(dataS) ## Create multiple chromosomes data <- list() for (cc in 1:3) { dataS$chromosome <- cc data[[cc]] <- dataS } data <- Reduce(rbind, data) str(data) message("*** segmentByPairedPSCBS() via futures ...") library("future") oplan <- plan() strategies <- c("sequential", "multisession") ## Test 'future.batchtools' futures? pkg <- "future.batchtools" if (require(pkg, character.only=TRUE)) { strategies <- c(strategies, "batchtools_local") } message("Future strategies to test: ", paste(sQuote(strategies), collapse=", ")) fits <- list() for (strategy in strategies) { message(sprintf("- segmentByPairedPSCBS() using '%s' futures ...", strategy)) plan(strategy) fit <- segmentByPairedPSCBS(data, seed=0xBEEF, verbose=TRUE) fits[[strategy]] <- fit equal <- all.equal(fit, fits[[1]]) if (!equal) { str(fit) str(fits[[1]]) print(equal) stop(sprintf("segmentByPairedPSCBS() using '%s' futures does not produce the same results as when using '%s' futures", strategy, names(fits)[1])) } } message("*** segmentByPairedPSCBS() via futures ... DONE") message("*** segmentByPairedPSCBS() via futures with known segments ...") fits <- list() dataT <- subset(data, chromosome == 1) gaps <- findLargeGaps(dataT, minLength=2e6) knownSegments <- gapsToSegments(gaps) for (strategy in strategies) { message(sprintf("- segmentByPairedPSCBS() w/ known segments using '%s' futures ...", strategy)) plan(strategy) fit <- segmentByPairedPSCBS(dataT, knownSegments=knownSegments, seed=0xBEEF, verbose=TRUE) fits[[strategy]] <- fit equal <- all.equal(fit, fits[[1]]) if (!equal) { str(fit) str(fits[[1]]) print(equal) stop(sprintf("segmentByPairedPSCBS() w/ known segments using '%s' futures does not produce the same results as when using '%s' futures", strategy, names(fits)[1])) } } message("*** segmentByPairedPSCBS() via futures ... DONE") ## Cleanup plan(oplan) rm(list=c("fits", "data", "fit")) PSCBS/tests/segmentByNonPairedPSCBS,medianDH.R0000644000176200001440000000463714564051545020432 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # Non-paired / tumor-only data data <- data[,c("chromosome", "x", "CT", "betaT")] str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=20),] # Fake a second chromosome dataT <- dataS dataT$chromosome <- 2L dataS <- rbind(dataS, dataT) rm(dataT) str(dataS) # Non-Paired PSCBS segmentation fit <- segmentByNonPairedPSCBS(dataS, avgDH="median", seed=0xBEEF, verbose=-10) print(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=100, verbose=-10) print(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance (AB) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in DH for calling AB # (which be done by default by the caller, if skipped here) deltaAB <- estimateDeltaAB(fit, flavor="qq(DH)", verbose=-10) print(deltaAB) fit <- callAB(fit, delta=deltaAB, verbose=-10) print(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaAB == deltaAB) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in loss-of-heterozygosity (LOH) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in C1 for calling LOH # (which be done by default by the caller, if skipped here) deltaLOH <- estimateDeltaLOH(fit, flavor="minC1|nonAB", verbose=-10) print(deltaLOH) fit <- callLOH(fit, delta=deltaLOH, verbose=-10) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaLOH == deltaLOH) PSCBS/tests/segmentByCBS,calls.R0000644000176200001440000000375614564051545016015 0ustar liggesusers# This test script calls a report generator which requires # the 'ggplot2' package, which in turn will require packages # 'colorspace', 'dichromat', 'munsell', 'reshape2' and 'scales'. # Only run this test in full testing mode if (Sys.getenv("_R_CHECK_FULL_") != "") { library("PSCBS") stext <- R.utils::stext # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) data <- data.frame(chromosome=data$chromosome, x=data$x, y=data$CT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # CBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=5),] str(dataS) gaps <- findLargeGaps(dataS, minLength=2e6) knownSegments <- gapsToSegments(gaps) # CBS segmentation fit <- segmentByCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) signalType(fit) <- "ratio" plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call using the UCSF MAD caller (not recommended) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitC <- callGainsAndLosses(fit) plotTracks(fitC) pars <- fitC$params$callGainsAndLosses stext(side=3, pos=1/2, line=-1, substitute(sigma==x, list(x=sprintf("%.2f", pars$sigmaMAD)))) mu <- pars$muR tau <- unlist(pars[c("tauLoss", "tauGain")], use.names=FALSE) abline(h=mu, lty=2, lwd=2) abline(h=tau, lwd=2) mtext(side=4, at=tau[1], expression(Delta[LOSS]), adj=-0.2, cex=0.7, las=2, xpd=TRUE) mtext(side=4, at=tau[2], expression(Delta[GAIN]), adj=-0.2, cex=0.7, las=2, xpd=TRUE) title(main="CN caller: \"ucsf-mad\"") # Caller to be implemented deltaCN <- estimateDeltaCN(fit) tau <- mu + 1/2*c(-1,+1)*deltaCN abline(h=tau, lty=2, lwd=1, col="red") } # if (Sys.getenv("_R_CHECK_FULL_")) PSCBS/tests/PairedPSCBS,boot.R0000644000176200001440000000535714564051545015373 0ustar liggesusers########################################################### # This tests: # - Bootstrapping for PairedPSCBS objects ########################################################### library("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) dataS <- dataS[seq(from=1, to=nrow(data), by=5),] nSegs <- 4L str(dataS) # Segment known regions knownSegments <- data.frame( chromosome = c( 1, 1, 1), start = c( -Inf, NA, 141510003), end = c(120992603, NA, +Inf) ) fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, avgDH="median", seed=0xBEEF) print(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - B <- 1L seed <- 0xBEEF probs <- c(0.025, 0.05, 0.95, 0.975) sets <- getBootstrapLocusSets(fit, B=B, seed=seed) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset by first segment # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ss <- 1L fitT <- extractSegment(fit, ss) dataT <- getLocusData(fitT) segsT <- getSegments(fitT) # Truth bootT <- bootstrapSegmentsAndChangepoints(fitT, B=B, seed=seed) bootT1 <- bootT$segments[1L,,,drop=FALSE] types <- dimnames(bootT1)[[3L]] dim(bootT1) <- dim(bootT1)[-1L] colnames(bootT1) <- types sumsT <- apply(bootT1, MARGIN=2L, FUN=quantile, probs=probs) print(sumsT) fitTB <- bootstrapTCNandDHByRegion(fitT, B=B, seed=seed) segsTB <- getSegments(fitTB) segsTB <- unlist(segsTB[,grep("_", colnames(segsTB))]) dim(segsTB) <- dim(sumsT) dimnames(segsTB) <- dimnames(sumsT) print(segsTB) # Sanity check stopifnot(all.equal(segsTB, sumsT)) # Calculate summaries using the existing bootstrap samples fitTBp <- bootstrapTCNandDHByRegion(fitT, .boot=bootT) # Sanity check all.equal(fitTBp, fitTB) # Bootstrap from scratch setsT <- getBootstrapLocusSets(fitT, B=B, seed=seed) lociT <- setsT$locusSet[[1L]]$bootstrap$loci idxs <- lociT$tcn tcnT <- array(dataT$CT[idxs], dim=dim(idxs)) tcnT <- apply(tcnT, MARGIN=2L, FUN=mean, na.rm=TRUE) idxs <- lociT$dh dhT <- array(dataT$rho[idxs], dim=dim(idxs)) dhT <- apply(dhT, MARGIN=2L, FUN=median, na.rm=TRUE) c1T <- (1-dhT) * tcnT / 2 c2T <- tcnT - c1T bootT2 <- array(c(tcnT, dhT, c1T, c2T), dim=c(1L, 4L)) colnames(bootT2) <- colnames(bootT1) print(bootT2) # This comparison is only valid if B == 1L if (B == 1L) { # Sanity check stopifnot(all.equal(bootT2, bootT1)) } PSCBS/tests/segmentByCBS.R0000644000176200001440000001071714564051545014715 0ustar liggesusers########################################################### # This tests: # - segmentByCBS(...) # - segmentByCBS(..., knownSegments) # - tileChromosomes() # - plotTracks() ########################################################### library("PSCBS") subplots <- R.utils::subplots # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 subplots(8, ncol=1L) par(mar=c(1.7,1,0.2,1)+0.1) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x) sampleName(fit) <- "CBS_Example" print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation with some known change points # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome=c( 0, 0), start =x[c( 1, 401)], end =x[c(349, J)] ) fit2 <- segmentByCBS(y, x=x, knownSegments=knownSegments, verbose=TRUE) sampleName(fit2) <- "CBS_Example_2" print(fit2) plotTracks(fit2) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Chromosome boundaries can be specified as -Inf and +Inf knownSegments <- data.frame( chromosome=c( 0, 0), start =c( -Inf, x[401]), end =c(x[349], +Inf) ) fit2b <- segmentByCBS(y, x=x, knownSegments=knownSegments, verbose=TRUE) sampleName(fit2b) <- "CBS_Example_2b" print(fit2b) plotTracks(fit2b) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # As a proof of concept, it is possible to segment just the centromere, # which contains no data. All statistics will be NAs. knownSegments <- data.frame( chromosome=c( 0), start =x[c(350)], end =x[c(400)] ) fit3 <- segmentByCBS(y, x=x, knownSegments=knownSegments, verbose=TRUE) sampleName(fit3) <- "CBS_Example_3" print(fit3) plotTracks(fit3, Clim=c(0,5), xlim=c(0,100)) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # If one specify the (empty) centromere as a segment, then its # estimated statistics will be NAs, which becomes a natural # separator between the two "independent" arms. knownSegments <- data.frame( chromosome=c( 0, 0, 0), start =x[c( 1, 350, 401)], end =x[c(349, 400, J)] ) fit4 <- segmentByCBS(y, x=x, knownSegments=knownSegments, verbose=TRUE) sampleName(fit4) <- "CBS_Example_4" print(fit4) plotTracks(fit4) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) fit5 <- segmentByCBS(y, x=x, knownSegments=knownSegments, undo=Inf, verbose=TRUE) sampleName(fit5) <- "CBS_Example_5" print(fit5) plotTracks(fit5) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) stopifnot(nbrOfSegments(fit5) == nrow(knownSegments)) # One can also force a separator between two segments by setting # 'start' and 'end' to NAs ('chromosome' has to be given) knownSegments <- data.frame( chromosome=c( 0, 0, 0), start =x[c( 1, NA, 401)], end =x[c(349, NA, J)] ) fit6 <- segmentByCBS(y, x=x, knownSegments=knownSegments, verbose=TRUE) sampleName(fit6) <- "CBS_Example_6" print(fit6) plotTracks(fit6) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segment multiple chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulate multiple chromosomes fit1 <- renameChromosomes(fit, from=0, to=1) fit2 <- renameChromosomes(fit, from=0, to=2) fitM <- c(fit1, fit2) fitM <- segmentByCBS(fitM) sampleName(fitM) <- "CBS_Example_M" print(fitM) plotTracks(fitM, Clim=c(-3,3)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tiling multiple chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes fitT <- tileChromosomes(fitM) fitTb <- tileChromosomes(fitT) stopifnot(identical(fitTb, fitT)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Write segmentation to file # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - pathT <- tempdir() ## Tab-delimited file pathname <- writeSegments(fitM, path=pathT) print(pathname) ## WIG file pathname <- writeWIG(fitM, path=pathT) print(pathname) unlink(pathT, recursive=TRUE) PSCBS/tests/segmentByCBS,weights.R0000644000176200001440000001151214564051545016356 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 x <- sort(runif(J, max=J)) * 1e5 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps outliers <- seq(from=1L, to=J, length.out=0.2*J) y[outliers] <- y[outliers] + 1.5 w <- rep(1.0, times=J) w[outliers] <- 0.01 data <- data.frame(chromosome=1L, x=x, y=y) dataW <- cbind(data, w=w) par(mar=c(2,3,0.2,1)+0.1) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Single-chromosome segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segment without weights fit <- segmentByCBS(data) sampleName(fit) <- "CBS_Example" print(fit) plotTracks(fit) ## Highlight outliers (they pull up the mean levels) points(x[outliers]/1e6, y[outliers], col="purple") # Segment with weights fitW <- segmentByCBS(dataW) sampleName(fitW) <- "CBS_Example (weighted)" print(fitW) drawLevels(fitW, col="red") legend("topright", bg="white", legend=c("outliers", "non-weighted CBS", "weighted CBS"), col=c("purple", "purple", "red"), lwd=c(NA,3,3), pch=c(1,NA,NA)) ## Assert that weighted segment means are less biased dmean <- getSegments(fit)$mean - getSegments(fitW)$mean cat("Segment mean differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation with some known change points # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- data.frame( chromosome=c( 1, 1), start =x[c( 1, 401)], end =x[c(349, J)] ) fit2 <- segmentByCBS(dataW, knownSegments=knownSegments, verbose=TRUE) sampleName(fit2) <- "CBS_Example_2 (weighted)" print(fit2) plotTracks(fit2) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # Chromosome boundaries can be specified as -Inf and +Inf knownSegments <- data.frame( chromosome=c( 1, 1), start =c( -Inf, x[401]), end =c(x[349], +Inf) ) fit2b <- segmentByCBS(dataW, knownSegments=knownSegments, verbose=TRUE) sampleName(fit2b) <- "CBS_Example_2b (weighted)" print(fit2b) plotTracks(fit2b) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # As a proof of concept, it is possible to segment just the centromere, # which contains no data. All statistics will be NAs. knownSegments <- data.frame( chromosome=c( 1), start =x[c(350)], end =x[c(400)] ) fit3 <- segmentByCBS(dataW, knownSegments=knownSegments, verbose=TRUE) sampleName(fit3) <- "CBS_Example_3" print(fit3) plotTracks(fit3, Clim=c(0,5), xlim=c(0,100)) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # If one specify the (empty) centromere as a segment, then its # estimated statistics will be NAs, which becomes a natural # separator between the two "independent" arms. knownSegments <- data.frame( chromosome=c( 1, 1, 1), start =x[c( 1, 350, 401)], end =x[c(349, 400, J)] ) fit4 <- segmentByCBS(dataW, knownSegments=knownSegments, verbose=TRUE) sampleName(fit4) <- "CBS_Example_4" print(fit4) plotTracks(fit4) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) fit5 <- segmentByCBS(dataW, knownSegments=knownSegments, undo=Inf, verbose=TRUE) sampleName(fit5) <- "CBS_Example_5" print(fit5) plotTracks(fit5) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) stopifnot(nbrOfSegments(fit5) == nrow(knownSegments)) # One can also force a separator between two segments by setting # 'start' and 'end' to NAs ('chromosome' has to be given) knownSegments <- data.frame( chromosome=c( 1, 1, 1), start =x[c( 1, NA, 401)], end =x[c(349, NA, J)] ) fit6 <- segmentByCBS(dataW, knownSegments=knownSegments, verbose=TRUE) sampleName(fit6) <- "CBS_Example_6" print(fit6) plotTracks(fit6) abline(v=c(knownSegments$start, knownSegments$end)/1e6, lty=3) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multi-chromosome segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data2 <- data data2$chromosome <- 2L data <- rbind(data, data2) dataW <- cbind(data, w=w) par(mar=c(2,3,0.2,1)+0.1) # Segment without weights fit <- segmentByCBS(data) sampleName(fit) <- "CBS_Example" print(fit) plotTracks(fit, Clim=c(-3,3)) # Segment with weights fitW <- segmentByCBS(dataW) sampleName(fitW) <- "CBS_Example (weighted)" print(fitW) drawLevels(fitW, col="red") legend("topright", bg="white", legend=c("outliers", "non-weighted CBS", "weighted CBS"), col=c("purple", "purple", "red"), lwd=c(NA,3,3), pch=c(1,NA,NA)) ## Assert that weighted segment means are less biased dmean <- getSegments(fit)$mean - getSegments(fitW)$mean cat("Segment mean differences:\n") print(dmean) stopifnot(all(dmean > 0, na.rm=TRUE)) PSCBS/tests/segmentByPairedPSCBS,report.R0000644000176200001440000000240314564051545017606 0ustar liggesusers# This test script calls a report generator which requires # the 'ggplot2' package, which in turn will require packages # 'colorspace', 'dichromat', 'munsell', 'reshape2' and 'scales'. # Only run this test in full testing mode if (Sys.getenv("_R_CHECK_FULL_") != "") { library("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=5),] str(dataS) gaps <- findLargeGaps(dataS, minLength=2e6) knownSegments <- gapsToSegments(gaps) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(dataS, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) # Fake a multi-chromosome segmentation fit1 <- fit fit2 <- renameChromosomes(fit, from=1, to=2) fit <- c(fit1, fit2) report(fit, sampleName="PairedPSCBS", studyName="PSCBS-Ex", verbose=-10) } # if (Sys.getenv("_R_CHECK_FULL_")) PSCBS/tests/segmentByCBS,prune.R0000644000176200001440000000253114564051545016036 0ustar liggesuserslibrary("PSCBS") ## Compare segments assertMatchingSegments <- function(fitM, fit) { chrs <- getChromosomes(fitM) segsM <- lapply(chrs, FUN=function(chr) { getSegments(extractChromosome(fitM, chr)) }) segs <- lapply(fit[chrs], FUN=getSegments) stopifnot(all.equal(segsM, segs, check.attributes=FALSE)) } ## Simulate data set.seed(0xBEEF) J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 data <- list() for (chr in 1:2) { data[[chr]] <- data.frame(chromosome=chr, x=x, y=y) } data$M <- Reduce(rbind, data) ## Segment message("*** segmentByCBS()") fit <- lapply(data, FUN=segmentByCBS) print(fit) assertMatchingSegments(fit$M, fit) ## Join segments message("*** joinSegments()") fitj <- lapply(fit, FUN=joinSegments) print(fitj) assertMatchingSegments(fitj$M, fitj) ## Reset segments message("*** resetSegments()") fitj <- lapply(fit, FUN=resetSegments) print(fitj) assertMatchingSegments(fitj$M, fitj) ## Prune by SD undo message("*** pruneBySdUndo()") fitp <- lapply(fit, FUN=pruneBySdUndo) print(fitp) assertMatchingSegments(fitp$M, fitp) ## Prune by hierarchical clustering message("*** pruneByHClust()") fitp <- lapply(fit, FUN=pruneByHClust, k=1L) print(fitp) assertMatchingSegments(fitp$M, fitp) PSCBS/tests/segmentByPairedPSCBS,noNormalBAFs.R0000644000176200001440000000375514564051545020567 0ustar liggesuserslibrary("PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Run light-weight tests by default if (Sys.getenv("_R_CHECK_FULL_") == "") { # Use only every 5th data point dataS <- dataS[seq(from=1, to=nrow(data), by=5),] # Number of segments (for assertion) nSegs <- 3L # Number of bootstrap samples (see below) B <- 100L } else { # Full tests nSegs <- 8L B <- 1000L } str(dataS) R.oo::attachLocally(dataS) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulate that genotypes are known by other means # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - library("aroma.light") muN <- aroma.light::callNaiveGenotypes(betaN, censorAt=c(0,1)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByPairedPSCBS(CT, betaT=betaT, muN=muN, tbn=FALSE, chromosome=chromosome, x=x, seed=0xBEEF, verbose=-10) print(fit) # Plot results plotTracks(fit) # Sanity check stopifnot(nbrOfSegments(fit) == nSegs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=B, verbose=-10) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance 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e8d89580cd99dc842d45eb2368ea9bed *vignettes/PairedPSCBS.tex.rsp f3907cf5bef1f44c8c15558e94274a18 *vignettes/natbib.bst PSCBS/R/0000755000176200001440000000000015000476724011332 5ustar liggesusersPSCBS/R/PairedPSCBS.estimateDeltaAB.R0000644000176200001440000004733014564051545016456 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateDeltaAB # # @title "Estimate a threshold for calling allelic balance from DH" # # \description{ # @get "title" to be used by the @seemethod "callAB" method. # } # # @synopsis # # \arguments{ # \item{scale}{An optional @numeric scale factor.} # \item{flavor}{A @character string specifying which type of # estimator to use.} # \item{...}{Additional arguments passed to the estimator.} # \item{max}{(Optional) The maximum estimate allowed. If greater than # this value, the estimate will be truncated.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the threshold estimate as a @numeric scalar. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "estimateDeltaABBySmallDH", # @seemethod "estimateStdDevForHeterozygousBAF", # @seemethod "estimateMeanForDH", and # @seemethod "estimateHighDHQuantileAtAB". # } # #*/########################################################################### setMethodS3("estimateDeltaAB", "PairedPSCBS", function(this, scale=NULL, flavor=c("qq(DH)", "q(DH)", "mad(hBAF)", "median(DH)"), ..., max=Inf, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'max': max <- Arguments$getDouble(max, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating DH threshold for calling allelic imbalances") verbose && cat(verbose, "flavor: ", flavor) if (flavor == "mad(hBAF)") { if (is.null(scale)) scale <- 3 verbose && cat(verbose, "scale: ", scale) # sigma = mad(hBAF) = 1.4826*median(|hBAF-m|), # where m = median(hBAF) ~= 1/2 sd <- estimateStdDevForHeterozygousBAF(this, ..., verbose=verbose) verbose && printf(verbose, "sd: %.3g\n", sd) delta <- scale * sd } else if (flavor == "median(DH)") { if (is.null(scale)) scale <- 3 verbose && cat(verbose, "scale: ", scale) # sigma = 1/2*1.4826*median(|hBAF-1/2|), # because DH = 2*|hBAF-1/2| mu <- estimateMeanForDH(this, ..., verbose=verbose) verbose && printf(verbose, "mu: %.3g\n", mu) sd <- 1/2 * 1.4826 * mu verbose && printf(verbose, "sd: %.3g\n", sd) delta <- scale * sd } else if (flavor == "q(DH)") { if (is.null(scale)) scale <- 1 verbose && cat(verbose, "scale: ", scale) delta <- estimateHighDHQuantileAtAB(this, scale=scale, ..., verbose=verbose) } else if (flavor == "qq(DH)") { if (is.null(scale)) scale <- 1 verbose && cat(verbose, "scale: ", scale) delta <- estimateDeltaABBySmallDH(this, ..., verbose=verbose) delta <- scale * delta } else { stop("Unkown flavor: ", flavor) } ## } else if (flavor == "DHskew") { ## fit <- this ## if (is.null(fit$output$dhSkew)) { ## verbose && enter(verbose, "Estimating DH skewness for each segment") ## fit <- applyByRegion(fit, FUN=.addTcnDhStatitics, verbose=less(verbose, 5)) ## verbose && exit(verbose) ## } ## mu <- fit$output$dhMean ## skew <- fit$output$dhSkew ## ## deltaSkew <- -0.55 ## keep <- which(skew < deltaSkew) ## verbose && printf(verbose, "Number of segments heavily skewed (< %.3f): %d\n", deltaSkew, length(keep)) ## # Sanity check ## if (length(keep) == 0) { ## stop("Cannot estimate DH threshold for AB. No segments with strong skewness exists.") ## } ## deltaDH <- median(mu[keep], na.rm=TRUE) ## verbose && printf(verbose, "deltaDH: %.3g\n", deltaDH) ## deltaDH <- 1.10*deltaDH ## verbose && printf(verbose, "Adjusted +10%% deltaDH: %.3g\n", deltaDH) ## ## # sigma = 1/2*1.4826*median(|hBAF-1/2|), ## # because DH = 2*|hBAF-1/2| ## mu <- estimateMeanForDH(this, delta=deltaDH, ...) ## verbose && printf(verbose, "mu: %.3g\n", mu) ## sd <- 1/2 * 1.4826 * mu ## verbose && printf(verbose, "sd: %.3g\n", sd) ## } verbose && printf(verbose, "Estimated delta: %.3g\n", delta) # Truncate estimate? if (delta > max) { warning("Estimated delta (%.3g) was greater than the maximum allowed value (%.3g). The latter will be used instead.", delta, max) delta <- max verbose && printf(verbose, "Max delta: %.3g\n", max) verbose && printf(verbose, "Truncated delta: %.3g\n", delta) } verbose && exit(verbose) delta }) # estimateDeltaAB() setMethodS3("estimateStdDevForHeterozygousBAF", "PairedPSCBS", function(this, deltaDH=0.20, deltaTCN=5, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'deltaDH': deltaDH <- Arguments$getDouble(deltaDH, range=c(0,1)) # Argument 'deltaTCN': deltaTCN <- Arguments$getDouble(deltaTCN, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating standard deviation of tumor BAFs for heterozygous SNPs") verbose && cat(verbose, "DH threshold: ", deltaDH) verbose && cat(verbose, "TCN threshold: ", deltaTCN) segs <- as.data.frame(this) verbose && cat(verbose, "Number of segments: ", nrow(segs)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find segments to be used for the estimation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find segments that have low DHs idxsDH <- which(segs$dhMean <= deltaDH) verbose && cat(verbose, "Identified segments with small DH levels: ", length(idxsDH)) verbose && str(verbose, idxsDH) # Sanity check if (length(idxsDH) == 0) { stop("Cannot estimate standard deviation. There exist no segments with DH less or equal to the given threshold: ", deltaDH) } # Find segments that have low TCNs idxsTCN <- which(segs$tcnMean <= deltaTCN) verbose && cat(verbose, "Identified segments with small TCN levels: ", length(idxsTCN)) verbose && str(verbose, idxsTCN) # Sanity check if (length(idxsTCN) == 0) { stop("Cannot estimate standard deviation. There exist no segments with TCN less or equal to the given threshold: ", deltaTCN) } # Segments with small DH and small TCN idxs <- intersect(idxsDH, idxsTCN) verbose && cat(verbose, "Identified segments with small DH and small TCN levels: ", length(idxs)) verbose && str(verbose, idxs) # Sanity check if (length(idxs) == 0) { stop("Cannot estimate standard deviation. There exist no segments with small DH and small TCN.") } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimate parameters # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract those segments verbose && enter(verbose, "Extracting identified segments") fitT <- extractRegions(this, idxs) verbose && exit(verbose) # Get the tumor BAFs for the heterozygous SNPs verbose && enter(verbose, "Extracting BAFs for the heterozygous SNPs") beta <- with(fitT$data, betaTN[muN == 1/2]) verbose && str(verbose, beta) verbose && exit(verbose) # Estimate the standard deviation for those sd <- mad(beta, na.rm=TRUE) verbose && cat(verbose, "Estimated standard deviation: ", sd) verbose && exit(verbose) sd }, private=TRUE) # estimateStdDevForHeterozygousBAF() setMethodS3("estimateMeanForDH", "PairedPSCBS", function(this, deltaDH=0.20, deltaTCN=5, robust=TRUE, trim=0.05, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'deltaDH': deltaDH <- Arguments$getDouble(deltaDH, range=c(0,1)) # Argument 'deltaTCN': deltaTCN <- Arguments$getDouble(deltaTCN, range=c(0,Inf)) # Argument 'robust': robust <- Arguments$getLogical(robust) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating mean of tumor DHs for heterozygous SNPs") verbose && cat(verbose, "DH threshold: ", deltaDH) verbose && cat(verbose, "TCN threshold: ", deltaTCN) verbose && cat(verbose, "Robust estimator: ", robust) verbose && cat(verbose, "Trim: ", trim) segs <- as.data.frame(this) verbose && cat(verbose, "Number of segments: ", nrow(segs)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find segments to be used for the estimation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find segments that have low DHs idxsDH <- which(segs$dhMean <= deltaDH) verbose && cat(verbose, "Identified segments with small DH levels: ", length(idxsDH)) verbose && str(verbose, idxsDH) # Sanity check if (length(idxsDH) == 0) { stop("Cannot estimate standard deviation. There exist no segments with DH less or equal to the given threshold: ", deltaDH) } # Find segments that have low TCNs idxsTCN <- which(segs$tcnMean <= deltaTCN) verbose && cat(verbose, "Identified segments with small TCN levels: ", length(idxsTCN)) verbose && str(verbose, idxsTCN) # Sanity check if (length(idxsTCN) == 0) { stop("Cannot estimate standard deviation. There exist no segments with TCN less or equal to the given threshold: ", deltaTCN) } # Segments with small DH and small TCN idxs <- intersect(idxsDH, idxsTCN) verbose && cat(verbose, "Identified segments with small DH and small TCN levels: ", length(idxs)) verbose && str(verbose, idxs) # Sanity check if (length(idxs) == 0) { stop("Cannot estimate standard deviation. There exist no segments with small DH and small TCN.") } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimate parameters # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract those segments verbose && enter(verbose, "Extracting identified segments") fitT <- extractRegions(this, idxs) verbose && exit(verbose) # Get the tumor DHs for the heterozygous SNPs verbose && enter(verbose, "Extracting DHs for the heterozygous SNPs") rho <- with(fitT$data, rho[muN == 1/2]) verbose && str(verbose, rho) verbose && exit(verbose) # Estimate the average for those rho <- rho[is.finite(rho)] if (robust) { mu <- median(rho, na.rm=FALSE) qlow <- quantile(rho, probs=0.05, na.rm=FALSE) delta <- mu-qlow print(list(qlow=qlow, mu=mu, delta=delta, "mu+delta"=mu+delta)) } else { mu <- mean(rho, trim=trim, na.rm=FALSE) } verbose && cat(verbose, "Estimated mean: ", mu) verbose && exit(verbose) mu }, private=TRUE) # estimateMeanForDH() setMethodS3("estimateHighDHQuantileAtAB", "PairedPSCBS", function(this, quantile=0.99, scale=1, deltaDH=0.20, deltaTCN=5, robust=TRUE, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'quantile': quantile <- Arguments$getDouble(quantile, range=c(0.5,1)) # Argument 'scale': scale <- Arguments$getDouble(scale, range=c(0,Inf)) # Argument 'deltaDH': deltaDH <- Arguments$getDouble(deltaDH, range=c(0,1)) # Argument 'deltaTCN': deltaTCN <- Arguments$getDouble(deltaTCN, range=c(0,Inf)) # Argument 'robust': robust <- Arguments$getLogical(robust) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating DH quantile of tumor DHs for heterozygous SNPs") verbose && cat(verbose, "DH threshold: ", deltaDH) verbose && cat(verbose, "TCN threshold: ", deltaTCN) verbose && cat(verbose, "Robust estimator: ", robust) verbose && cat(verbose, "Scale factor: ", scale) segs <- as.data.frame(this) verbose && cat(verbose, "Number of segments: ", nrow(segs)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find segments to be used for the estimation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Finding some segments that are likely to in allelic balance (AB)") # Find some segments that have low DHs idxsDH <- which(segs$dhMean <= deltaDH) verbose && cat(verbose, "Identified segments with small DH levels: ", length(idxsDH)) verbose && str(verbose, idxsDH) # Sanity check if (length(idxsDH) == 0) { stop("Cannot estimate standard deviation. There exist no segments with DH less or equal to the given threshold: ", deltaDH) } # Find segments that have low TCNs idxsTCN <- which(segs$tcnMean <= deltaTCN) verbose && cat(verbose, "Identified segments with small TCN levels: ", length(idxsTCN)) verbose && str(verbose, idxsTCN) # Sanity check if (length(idxsTCN) == 0) { stop("Cannot estimate standard deviation. There exist no segments with TCN less or equal to the given threshold: ", deltaTCN) } # Segments with small DH and small TCN idxs <- intersect(idxsDH, idxsTCN) verbose && cat(verbose, "Identified segments with small DH and small TCN levels: ", length(idxs)) verbose && str(verbose, idxs) # Sanity check if (length(idxs) == 0) { stop("Cannot estimate standard deviation. There exist no segments with small DH and small TCN.") } # Extract those segments verbose && enter(verbose, "Extracting identified segments") fitT <- extractRegions(this, idxs) verbose && exit(verbose) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimate parameters # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get the tumor DHs for the heterozygous SNPs verbose && enter(verbose, "Extracting DHs for the heterozygous SNPs") rho <- with(fitT$data, rho[muN == 1/2]) verbose && str(verbose, rho) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Estimating the DH quantile # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Estimating the quantile of interest") verbose && cat(verbose, "Quantile: ", quantile) # Drop missing values rho <- rho[is.finite(rho)] if (robust) { lq <- quantile(rho, probs=1-quantile, na.rm=FALSE) verbose && printf(verbose, "Estimated lower quantile (%.3f): %f\n", 1-quantile, lq) mu <- median(rho, na.rm=FALSE) verbose && cat(verbose, "Estimated median: ", mu) delta <- mu-lq verbose && printf(verbose, "Estimated \"spread\": %f\n", delta) uq <- mu + scale*delta verbose && printf(verbose, "Scale parameter: %f\n", scale) qs <- c(lq, mu, mu+delta, uq) names(qs) <- sprintf("%.1f%%", 100*c(1-quantile, 0.5, quantile, 0.5+scale*(quantile-0.5))) names(qs)[3:4] <- sprintf("%s*", names(qs)[3:4]) attr(uq, "quantiles") <- qs } else { uq <- quantile(rho, probs=quantile, na.rm=FALSE) } names(uq) <- uq verbose && printf(verbose, "Estimated upper quantile (%.3f): %f\n", quantile, uq) verbose && exit(verbose) verbose && exit(verbose) uq }, private=TRUE) # estimateHighDHQuantileAtAB() ###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateDeltaABBySmallDH # # @title "Estimate a threshold for calling allelic balance from DH" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{q1}{A @numeric value specifying the weighted quantile of the # segment-level DHs used to identify segments with small DH means.} # \item{q2}{A @numeric value specifying the quantile of the locus-level # DH signals for those segments with small DH mean levels.} # \item{...}{Not used.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the threshold estimate as a @numeric scalar. # } # # \section{Algorithm}{ # \itemize{ # \item Grabs the segment-level DH estimates. # \item Calculate segment weights proportional to the number # of heterozygous SNPs. # \item Calculate \eqn{\Delta} as the 5\% quantile of the weighted DH means. # \item Choose the segments with means less than \eqn{\Delta}. # \item Calculate threshold \eqn{\Delta_{AB}} as the 90\% "symmetric" quantile # of the observed locus-level DHs from the selected segments # in Step 4. # The q:th "symmetric" quantile is estimated by estimating # the ((1-q), 50\%) quantiles, calculating their distance as # "50\%-(1-q)" and add to the median (50\%), i.e. # "median + (median-(1-q))" = "2*median-1 + q", which should # equal q if the distribution is symmetric. # } # } # # @author "HB" # # \seealso{ # Instead of calling this method explicitly, it is recommended # to use the @seemethod "estimateDeltaAB" method. # } # # @keyword internal #*/########################################################################### setMethodS3("estimateDeltaABBySmallDH", "PairedPSCBS", function(fit, q1=0.05, q2=0.90, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'q1' & 'q2': q1 <- Arguments$getDouble(q1, range=c(0,1)) q2 <- Arguments$getDouble(q2, range=c(0,1)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating DH threshold for AB caller") verbose && cat(verbose, "quantile #1: ", q1) verbose && cat(verbose, "Symmetric quantile #2: ", q2) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the region-level estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- getSegments(fit) dh <- segs$dhMean .stop_if_not(!is.null(dh)) n <- segs$dhNbrOfLoci # Drop missing values keep <- (!is.na(dh) & !is.na(n)) idxs <- which(keep) dh <- dh[idxs] n <- n[idxs] verbose && cat(verbose, "Number of segments: ", length(idxs)) # Sanity check .stop_if_not(length(idxs) > 0) # Calculated weighted quantile weights <- n / sum(n) deltaDH <- weightedQuantile(dh, w=weights, probs=q1) verbose && printf(verbose, "Weighted %g%% quantile of DH: %f\n", 100*q1, deltaDH) # Identify segments with DH this small keep <- (dh <= deltaDH) idxs <- idxs[keep] verbose && cat(verbose, "Number of segments with small DH: ", length(idxs)) # Sanity check .stop_if_not(length(idxs) > 0) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the locus-level estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the regions of interest fitT <- extractRegions(fit, idxs) # Extract the data data <- fitT$data rho <- data$rho .stop_if_not(!is.null(rho)) verbose && cat(verbose, "Number of data points: ", length(rho)) # Drop missing values rho <- rho[is.finite(rho)] verbose && cat(verbose, "Number of finite data points: ", length(rho)) qs <- quantile(rho, probs=c(1-q2, 1/2), na.rm=FALSE, names=FALSE) verbose && printf(verbose, "Estimate of (1-%.3g):th and 50%% quantiles: (%g,%g)\n", q2, qs[1], qs[2]) deltaAB <- qs[2] + (qs[2]-qs[1]) verbose && printf(verbose, "Estimate of %.3g:th \"symmetric\" quantile: %g\n", q2, deltaAB) # Sanity check deltaAB <- Arguments$getDouble(deltaAB) deltaAB }, protected=TRUE) # estimateDeltaABBySmallDH() PSCBS/R/PairedPSCBS.EXTS3.R0000644000176200001440000001043014564051545014323 0ustar liggesuserssetMethodS3("extractLocusLevelC1C2", "PairedPSCBS", function(fit, ...) { # Extract locus-level data data <- getLocusData(fit) C <- data$CT rho <- data$rho # Swapped (C1,C2) <-> (C2,C1) for some segments? fields <- colnames(getSegments(fit)) if (is.element("c1c2Swap", fields)) { # FIXME: When PSCBS is updated. # WORKAROUND: extractSegmentDataByLocus() in PSCBS v0.40.4 requires: # that fields "chromosome", "tcnStart", "tcnEnd" are always requested # /2014-03-21 c1c2Swap <- extractSegmentDataByLocus(fit, fields=c("c1c2Swap", "chromosome", "tcnStart", "tcnEnd")) c1c2Swap <- c1c2Swap[["c1c2Swap"]] if (any(c1c2Swap)) { rho[c1c2Swap] <- -rho[c1c2Swap] } } C1 <- 1/2*(1-rho)*C C2 <- C - C1 data.frame(C1=C1, C2=C2) }, private=TRUE) # extractLocusLevelC1C2() setMethodS3("extractLocusLevelTCN", "PairedPSCBS", function(fit, ...) { data <- getLocusData(fit) C <- data$CT }, private=TRUE) # extractLocusLevelTCN() setMethodS3("extractDhSegment", "PairedPSCBS", function(fit, idx, what=c("hets", "SNPs", "all"), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'what': what <- match.arg(what) segs <- getSegments(fit, splitters=TRUE) .stop_if_not(!is.null(segs)) nbrOfSegments <- nrow(segs) # Argument 'idx': idx <- Arguments$getIndex(idx, max=nbrOfSegments) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Extracting a specific DH segment") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) .stop_if_not(!is.null(data)) segs <- getSegments(fit, splitters=TRUE) .stop_if_not(!is.null(segs)) verbose && enter(verbose, "Subsetting segment") # Subset the region-level data seg <- segs[idx,,drop=FALSE] isDivider <- all(is.na(seg)) if (isDivider) { verbose && cat("Cannot extract DH segment. Not a valid segment: ", idx) verbose && exit(verbose) return(NULL) } verbose && print(verbose, seg) verbose && cat(verbose, "Number of TCN markers: ", sum(seg[["tcnNbrOfLoci"]], na.rm=TRUE)) verbose && exit(verbose) verbose && enter(verbose, "Subsetting data") units <- seq_len(nrow(data)) # Keep only chromosome of interest chr <- as.numeric(seg[,"chromosome"]) if (!is.na(chr)) { keep <- which(data$chromosome == chr) units <- units[keep] data <- data[keep,] } # Keep only loci within the segment xRange <- as.numeric(seg[,c("dhStart", "dhEnd")]) keep <- which(xRange[1] <= data$x & data$x <= xRange[2]) units <- units[keep] data <- data[keep,] muN <- data$muN isSnp <- is.finite(muN) # Keep only SNPs? if (is.element(what, c("SNPs", "hets"))) { keep <- which(isSnp) units <- units[keep] data <- data[keep,] } # Keep only heterozygous SNPs? if (what == "hets") { isHet <- (muN == 1/2) keep <- which(isHet) units <- units[keep] data <- data[keep,] } verbose && exit(verbose) n <- nrow(data) verbose && cat(verbose, "Number of loci in DH segment: ", n) # Special case? listOfDhLociNotPartOfSegment <- fit$listOfDhLociNotPartOfSegment if (!is.null(listOfDhLociNotPartOfSegment)) { tcnId <- seg[,"tcnId"] dhId <- seg[,"dhId"] dhLociNotPartOfSegment <- listOfDhLociNotPartOfSegment[[tcnId]] if (!is.null(dhLociNotPartOfSegment)) { lociToExclude <- dhLociNotPartOfSegment[[dhId]] verbose && cat(verbose, "Excluding loci that belongs to a flanking segment: ", length(lociToExclude)) drop <- match(lociToExclude, units) units <- units[-drop] data <- data[-drop,] n <- nrow(data) } } verbose && cat(verbose, "Number of units: ", n) verbose && cat(verbose, "Number of TCN markers: ", seg[,"tcnNbrOfLoci"]) # Sanity check if (what == "hets" && n > 0) .stop_if_not(n == seg[,"dhNbrOfLoci"]) fitS <- fit fitS$data <- data fitS$output <- seg verbose && exit(verbose) fitS }, protected=TRUE) # extractDhSegment() PSCBS/R/CBS.CALL.R0000644000176200001440000011401114564051545012600 0ustar liggesusers###########################################################################/** # @set "class=CBS" # @RdocMethod callGainsAndLosses # # @title "Calls gains and losses" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{adjust}{A positive scale factor adjusting the sensitivity of the # caller, where a value less (greater) than 1.0 makes the caller # less (more) sensitive.} # \item{method}{A @character string specifying the calling algorithm to use.} # \item{...}{Additional/optional arguments used to override the default # parameters used by the caller.} # } # # \value{ # Returns a @see "PSCBS::CBS" object where @logical columns # 'lossCall' and 'gainCall' have been appended to the segmentation table. # } # # \section{The UCSF caller}{ # If \code{method == "ucsf-mad"}, then segments are called using [1], i.e. # a segment is called gained or lost if its segment level is # at least two standard deviations away from the median segment level # on Chr1-22, where standard deviation is estimated using MAD. # Then same is done for \code{method == "ucsf-dmad"} with the difference # that the standard deviation is estimated using a robust first order # variance estimator. # } # # \examples{ # @include "../incl/segmentByCBS.Rex" # @include "../incl/segmentByCBS,calls.Rex" # } # # @author "HB" # # \references{ # [1] Fridlyand et al. \emph{Breast tumor copy number aberration # phenotypes and genomic instability}, BMC Cancer, 2006. \cr # } # # \seealso{ # @seemethod "callAmplifications". # @seemethod "callOutliers". # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("callGainsAndLosses", "CBS", function(fit, adjust=1.0, method=c("ucsf-mad", "ucsf-dmad"), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'adjust': adjust <- Arguments$getDouble(adjust, range=c(0, Inf)) # Argument 'method': method <- match.arg(method) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments that are gained or lost") userArgs <- list(...) params <- list() # Allocate calls naValue <- NA nbrOfSegments <- nbrOfSegments(fit, splitters=TRUE) segs <- getSegments(fit, splitters=TRUE) nbrOfRows <- nrow(segs) gainCalls <- lossCalls <- rep(naValue, times=nbrOfRows) verbose && cat(verbose, "Number of segments to be called: ", nbrOfSegments) verbose && cat(verbose, "Call method: ", method) if (is.element(method, c("ucsf-mad", "ucsf-dmad"))) { # Default arguments args <- list( chromosomes = intersect(getChromosomes(fit), c(0L, 1:22)), scale = 2.0 ) # Override by (optional) user-specified arguments for (key in names(userArgs)) { args[[key]] <- userArgs[[key]] } # Extract arguments chromosomes <- args$chromosomes scale <- args$scale # Argument check chromosomes <- Arguments$getVector(chromosomes, lengths=c(1,Inf)) scale <- Arguments$getDouble(scale, range=c(0,Inf)) # Estimate the whole-genome standard deviation of the TCNs if (method == "ucsf-mad") { sigma <- estimateStandardDeviation(fit, chromosomes=chromosomes, method="res", estimator="mad") sigmaKey <- "sigmaMAD" } else if (method == "ucsf-dmad") { sigma <- estimateStandardDeviation(fit, chromosomes=chromosomes, method="diff", estimator="mad") sigmaKey <- "sigmaDelta" } else { stop("INTERNAL ERROR: Unknown method: ", method) } # Sanity check sigma <- Arguments$getDouble(sigma, range=c(0,Inf)) # Calculate the threshold tau <- scale * sigma # Make more or less sensitive tau <- adjust * tau verbose && cat(verbose, "Call parameters:") verbose && str(verbose, list(sigma=sigma, scale=scale, adjust=adjust)) # Calculate segment levels using the median estimator fitT <- updateMeans(fit, avg="median") segsT <- getSegments(fitT, splitters=TRUE) mu <- segsT$mean fitT <- segsT <- NULL # Not needed anymore # The median segmented level muR <- median(mu, na.rm=TRUE) # The threshold for losses tauLoss <- muR - tau # The threshold for gains tauGain <- muR + tau # Call lossCalls <- (mu <= tauLoss) # Losses gainCalls <- (mu >= tauGain) # Gains # Call parameters used params$method <- method params$adjust <- adjust params[[sigmaKey]] <- sigma params$scale <- scale params$muR <- muR params$tau <- tau params$tauLoss <- tauLoss params$tauGain <- tauGain } verbose && cat(verbose, "Number of called segments: ", length(lossCalls)) # Sanity check .stop_if_not(length(lossCalls) == nbrOfRows) .stop_if_not(length(gainCalls) == nbrOfRows) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update 'DNAcopy' object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (a) segmentation table segs <- getSegments(fit, splitters=TRUE) segs$lossCall <- lossCalls segs$gainCall <- gainCalls fit$output <- segs # (b) parameters allParams <- fit$params if (is.null(allParams)) { allParams <- list() } allParams$callGainsAndLosses <- params fit$params <- allParams verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return the updated 'CBS' object. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit }, private=TRUE) # callGainsAndLosses() ###########################################################################/** # @RdocMethod callAmplifications # # @title "Calls (focal) amplifications" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{adjust}{A positive scale factor adjusting the sensitivity of the # caller, where a value less (greater) than 1.0 makes the caller # less (more) sensitive.} # \item{maxLength}{A @double scalar specifying the maximum length of a segment # in order for it to be considered a focal amplification.} # \item{method}{A @character string specifying the calling algorithm to use.} # \item{...}{Additional/optional arguments used to override the default # parameters used by the caller.} # \item{verbose}{@see "R.utils::Verbose".} # } # # \value{ # Returns a @see "PSCBS::CBS" object where @logical column # 'amplificationCall' has been appended to the segmentation table. # } # # \section{The UCSF caller}{ # If \code{method == "ucsf-exp"}, then segments are called using [1], i.e. # a segment is called an amplification if ... # } # # @author # # \references{ # [1] Fridlyand et al. \emph{Breast tumor copy number aberration # phenotypes and genomic instability}, BMC Cancer, 2006. \cr # } # # \seealso{ # @seemethod "callGainsAndLosses". # @seemethod "callOutliers". # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("callAmplifications", "CBS", function(fit, adjust=1.0, maxLength=20e6, method=c("ucsf-exp"), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'adjust': adjust <- Arguments$getDouble(adjust, range=c(0, Inf)) # Argument 'maxLength': maxLength <- Arguments$getDouble(maxLength, range=c(0, Inf)) # Argument 'method': method <- match.arg(method) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments that are amplified") userArgs <- list(...) params <- list() # Allocate calls naValue <- NA nbrOfSegments <- nbrOfSegments(fit, splitters=TRUE) calls <- rep(naValue, times=nbrOfSegments) verbose && cat(verbose, "Number of segments to be called: ", nbrOfSegments) verbose && cat(verbose, "Call method: ", method) if (method == "ucsf-exp") { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Default arguments args <- list( minLevel = 0.0, lambda = 1.0, degree = 3 ) # Override by (optional) user-specified arguments for (key in names(userArgs)) { args[[key]] <- userArgs[[key]] } # Extract arguments minLevel <- args$minLevel lambda <- args$lambda degree <- args$degree # Validate arguments minLevel <- Arguments$getDouble(minLevel, range=c(-Inf, Inf)) lambda <- Arguments$getDouble(lambda, range=c(0, Inf)) degree <- Arguments$getDouble(degree, range=c(1, Inf)) verbose && cat(verbose, "Call parameters:") verbose && str(verbose, list(minLevel=minLevel, lambda=lambda, degree=degree)) segs <- getSegments(fit, splitters=TRUE) verbose && cat(verbose, "Segments:") verbose && str(verbose, segs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Rule #1: Only consider segments that are short enough # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # The lengths (in bp) of the segments start <- segs$start end <- segs$end length <- end - start ## + 1L keep1 <- (length <= maxLength) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Rule #2: Only consider segments that have a mean level # that is large enough. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # The mean levels of the segments mu <- segs$mean keep2 <- (mu >= minLevel) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Rule #3: Only consider segments that have a mean level # that is much larger than either of the # flanking segments. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # The mean levels of the flanking segments muL <- c(NA_real_, mu[-nbrOfSegments]) muR <- c(mu[-1], NA_real_) # The difference in mean levels to the flanking segments deltaL <- mu - muL deltaR <- mu - muR # The maximum difference to either of the flanking segments delta <- pmax(deltaL, deltaR, na.rm=TRUE) # The threshold for calling segments amplified tau <- exp(-lambda * mu^degree) # Make more or less sensitive tau <- adjust * tau keep3 <- (delta >= tau) # Amplification calls calls <- (keep1 & keep2 & keep3) # Call parameters used params$method <- method params$adjust <- adjust params$maxLength <- maxLength params$minLevel <- minLevel params$lambda <- lambda params$degree <- degree params$tau <- tau } verbose && cat(verbose, "Number of called segments: ", length(calls)) # Sanity check .stop_if_not(length(calls) == nbrOfSegments) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update 'DNAcopy' object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (a) segmentation table segs <- getSegments(fit, splitters=TRUE) segs$amplificationCall <- calls fit$output <- segs # (b) parameters allParams <- fit$params if (is.null(allParams)) { allParams <- list() } allParams$callAmplifications <- params fit$params <- allParams verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return the updated 'CBS' object. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit }, private=TRUE) # callAmplifications() ###########################################################################/** # @RdocMethod callOutliers # # @title "Calls outliers" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{adjust}{A positive scale factor adjusting the sensitivity of the # caller, where a value less (greater) than 1.0 makes the caller # less (more) sensitive.} # \item{method}{A @character string specifying the calling algorithm to use.} # \item{...}{Additional/optional arguments used to override the default # parameters used by the caller.} # } # # \value{ # Returns a @see "PSCBS::CBS" object where @logical columns # 'negOutlierCall' and 'posOutlierCall' have been appended # to the segmentation table. # } # # \section{The UCSF caller}{ # If \code{method == "ucsf-mad"}, then loci are called using [1] # "Finally, to identify single technical or biological outliers such # as high level amplifications, the presence of the outliers within # a segment was allowed by assigning the original observed log2ratio # to the clones for which the observed values were more than four # tumor-specific MAD away from the smoothed values." [1; Suppl. Mat.] # } # # @author "HB" # # \references{ # [1] Fridlyand et al. \emph{Breast tumor copy number aberration # phenotypes and genomic instability}, BMC Cancer, 2006. \cr # } # # \seealso{ # @seemethod "callGainsAndLosses". # @seemethod "callAmplifications". # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("callOutliers", "CBS", function(fit, adjust=1.0, method=c("ucsf-mad"), ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'adjust': adjust <- Arguments$getDouble(adjust, range=c(0, Inf)) # Argument 'method': method <- match.arg(method) userArgs <- list(...) params <- list() # Allocate calls nbrOfLoci <- nbrOfLoci(fit) naValue <- NA negOutlierCall <- posOutlierCall <- rep(naValue, times=nbrOfLoci) if (method == "ucsf-mad") { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Default arguments args <- list( scale = 4.0 ) # Override by (optional) user-specified arguments for (key in names(userArgs)) { args[[key]] <- userArgs[[key]] } # Extract arguments scale <- args$scale # Validate arguments scale <- Arguments$getDouble(scale, range=c(0, Inf)) # Genomic annotations data <- getLocusData(fit) chromosome <- data$chromosome x <- data$x # CN signals y <- data[,3] # Segmented CN signals yS <- extractSegmentMeansByLocus(fit) # CN residuals (relative to segment means) dy <- y - yS segs <- getSegments(fit, splitters=TRUE) # Allocate per-segment SD estimates nbrOfSegments <- nbrOfSegments(fit) naValue <- NA_real_ sds <- rep(naValue, times=nbrOfSegments) naValue <- NA_real_ for (ss in seq_len(nbrOfSegments)) { seg <- segs[ss,] # Identify loci in current segment idxs <- which(seg$chromosome == chromosome & seg$start <= x & x <= seg$end) # Sanity check idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) # Extract CN residuals dySS <- dy[idxs] # Calculate MAD for segment sdSS <- mad(dySS, na.rm=TRUE) # Threshold for outliers tau <- scale * sdSS # Make more or less sensitive tau <- adjust * tau # Call outliers naValue <- NA callsSS <- rep(naValue, times=length(dySS)) callsSS[-tau <= dySS & dySS <= +tau] <- 0L callsSS[dySS > +tau] <- +1L callsSS[dySS < -tau] <- -1L # Record negOutlierCall[idxs] <- (callsSS < 0L) posOutlierCall[idxs] <- (callsSS > 0L) sds[ss] <- sdSS } # for (ss ...) params$method <- method params$adjust <- adjust params$scale <- scale params$sds <- sds } # Sanity check .stop_if_not(length(negOutlierCall) == nbrOfLoci) .stop_if_not(length(posOutlierCall) == nbrOfLoci) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update 'DNAcopy' object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (a) segmentation table data <- getLocusData(fit) data$negOutlierCall <- negOutlierCall data$posOutlierCall <- posOutlierCall fit$data <- data # (b) parameters allParams <- fit$params if (is.null(allParams)) { allParams <- list() } allParams$callOutliers <- params fit$params <- allParams # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return the updated 'CBS' object. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit }, private=TRUE) # callOutliers() setMethodS3("extractCallsByLocus", "CBS", function(fit, ...) { # Extract locus data data <- getLocusData(fit, ...) nbrOfLoci <- nrow(data) # Extract segment data segs <- getSegments(fit, splitters=TRUE) # Identify segment calls callCols <- grep("Call$", colnames(segs)) nbrOfCalls <- length(callCols) chromosome <- data$chromosome x <- data$x y <- data[,3] # Allocate locus calls naValue <- NA callsL <- matrix(naValue, nrow=nbrOfLoci, ncol=nbrOfCalls) colnames(callsL) <- colnames(segs)[callCols] callsL <- as.data.frame(callsL) # For each segment... for (ss in seq_len(nrow(segs))) { seg <- segs[ss,] idxs <- which(chromosome == seg$chromosome & seg$start <= x & x <= seg$end) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) # Sanity check ## .stop_if_not(length(idxs) == seg$nbrOfLoci) callsSS <- seg[callCols] for (cc in seq_len(nbrOfCalls)) { callsL[idxs,cc] <- callsSS[,cc] } } # for (ss ...) # The calls for loci that have missing annotations or observations, # should also be missing, i.e. NA. nok <- (is.na(chromosome) | is.na(x) | is.na(y)) callsL[nok,] <- NA # Sanity check .stop_if_not(nrow(callsL) == nbrOfLoci) .stop_if_not(ncol(callsL) == nbrOfCalls) callsL }, private=TRUE) # extractCallsByLocus() ###########################################################################/** # @RdocMethod getCallStatistics # # @title "Calculates various call statistics per chromosome" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{regions}{An optional @data.frame with columns "chromosome", # "start", and "end" specifying the regions of interest to calculate # statistics for. If @NULL, all of the genome is used.} # \item{shrinkRegions}{If @TRUE, regions are shrunk to the support of # the data.} # \item{...}{Not used.} # \item{verbose}{@see "R.utils::Verbose".} # } # # \value{ # Returns a CxK @data.frame, where C is the number of regions that # meet the criteria setup by argument \code{regions} # and (K-4)/2 is the number of call types. # The first column is the chromosome index, the second and the third # are the first and last position, and the fourth the length # (=last-first+1) of the chromosome. # The following columns contains call summaries per chromosome. # For each chromosome and call type, the total length of such calls # on that chromosome is reported together how large of a fraction # of the chromosome such calls occupy. # } # # \details{ # The estimators implemented here are based solely on the # segmentation results, which is very fast. # In the original proposal by Fridlyand et al. [1], the authors # estimates the parameters by converting segment-level calls back # to locus-level calls and there do the calculations. # The difference between the two approaches should be minor, # particularly for large density arrays. # } # # @author "HB" # # \references{ # [1] Fridlyand et al. \emph{Breast tumor copy number aberration # phenotypes and genomic instability}, BMC Cancer, 2006. \cr # } # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("getCallStatistics", "CBS", function(fit, regions=NULL, shrinkRegions=TRUE, ..., verbose=FALSE) { # To please R CMD check, cf. subset() chromosome <- NULL; rm(list="chromosome") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'regions': if (is.null(regions)) { # Get chromosome lengths regions <- getChromosomeRanges(fit)[,c("chromosome", "start", "end")] } regions <- as.data.frame(regions) .stop_if_not(all(is.element(c("chromosome", "start", "end"), colnames(regions)))) .stop_if_not(!any(duplicated(regions$chromosome))) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calculating call statistics") segs <- getSegments(fit, splitters=FALSE) callTypes <- grep("Call$", colnames(segs), value=TRUE) verbose && cat(verbose, "Call types: ", hpaste(callTypes)) if (length(callTypes) == 0) { stop("Cannot calculate call statistics. No calls have been made.") } verbose && cat(verbose, "Regions of interest:") verbose && str(verbose, regions) verbose && enter(verbose, "Filtering out segments within the requested regions") # Filter out segments within the requested regions segsT <- NULL verbose && cat(verbose, "Number of segments (before): ", nrow(segs)) for (rr in seq_len(nrow(regions))) { regionRR <- regions[rr,] chrRR <- regionRR[,"chromosome"] startRR <- regionRR[,"start"] endRR <- regionRR[,"end"] if (is.na(chrRR) || is.na(startRR) || is.na(endRR)) { next } verbose && enter(verbose, sprintf("Region #%d of %d", rr, nrow(regions))) # Select regions that (at least) overlapping with the region segsRR <- subset(segs, chromosome == chrRR & start <= endRR & end >= startRR) verbose && cat(verbose, "Number of segments within region: ", nrow(segsRR)) # Special case if (nrow(segsRR) == 0) { segsRR <- segs[1,][NA,] segsRR$chromosome <- chrRR segsRR$start <- startRR segsRR$end <- endRR segsRR$nbrOfLoci <- 0L } if (shrinkRegions) { range <- range(c(segsRR$start, segsRR$end), na.rm=TRUE) startRR <- max(startRR, range[1], na.rm=TRUE) endRR <- min(endRR, range[2], na.rm=TRUE) regions[rr,"end"] <- endRR regions[rr,"start"] <- startRR } # Adjust ranges segsRR$start[segsRR$start < startRR] <- startRR segsRR$end[segsRR$end > endRR] <- endRR segsRR$fullLength <- endRR - startRR ## + 1L segsT <- rbind(segsT, segsRR) verbose && exit(verbose) } # for (rr ...) segs <- segsT # Order by chromosome o <- order(segs$chromosome) segs <- segs[o,] verbose && cat(verbose, "Number of segments (after): ", nrow(segs)) verbose && str(verbose, segs) verbose && exit(verbose) verbose && enter(verbose, "Calculating total length per call and chromosome") # Sum length of calls per type and chromosome segs$length <- segs[,"end"] - segs[,"start"] ## + 1L res <- lapply(callTypes, FUN=function(type) { coeffs <- as.integer(segs[,type]) lens <- coeffs * segs$length lens <- by(lens, INDICES=segs$chromosome, FUN=sum, na.rm=TRUE) as.vector(lens) }) names(res) <- gsub("Call$", "Length", callTypes) res1 <- as.data.frame(res) verbose && str(verbose, res) verbose && exit(verbose) # Extract selected regions idxs <- match(unique(segs$chromosome), regions$chromosome) regionsT <- regions[idxs,] # Sanity check .stop_if_not(nrow(regionsT) == nrow(res1)) verbose && enter(verbose, "Calculating fractions per region") # Calculate lengths regionsT$length <- regionsT[,"end"] - regionsT[,"start"] ## + 1L .stop_if_not(all(regionsT$length >= 0)) res2 <- res1 / regionsT[,"length"] names(res2) <- gsub("Call$", "Fraction", callTypes) verbose && exit(verbose) res3 <- cbind(res1, res2) res <- regionsT if (nrow(res3) > 0) { res <- cbind(res, res3) } rownames(res) <- NULL res <- cbind(label=I(sprintf("chr%d", res[,"chromosome"])), res) # Sanity checks resT <- res[,grep("Fraction", colnames(res))] for (key in colnames(resT)) { rho <- resT[,key] .stop_if_not(all(rho >= 0, na.rm=TRUE)) .stop_if_not(all(rho <= 1, na.rm=TRUE)) } .stop_if_not(nrow(res) == nrow(regions)) verbose && str(verbose, res) verbose && exit(verbose) res }, protected=TRUE) # getCallStatistics() ###########################################################################/** # @RdocMethod getFractionOfGenomeLost # @aliasmethod getFractionOfGenomeGained # @aliasmethod getFractionOfGenomeAltered # @aliasmethod getFGL # @aliasmethod getFGG # @aliasmethod getFGA # # @title "Calculates the fraction of the genome lost, gained, or aberrant either way" # # \description{ # @get "title" (in sense of total copy numbers), # using definitions closely related to those presented in [1]. # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a @double in [0,1]. # } # # @author "HB" # # \references{ # [1] Fridlyand et al. \emph{Breast tumor copy number aberration # phenotypes and genomic instability}, BMC Cancer, 2006. \cr # } # # \seealso{ # Internally, @seemethod "getCallStatistics" is used. # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("getFractionOfGenomeLost", "CBS", function(fit, ...) { stats <- getCallStatistics(fit, ...) mean(stats$lossFraction, na.rm=TRUE) }, protected=TRUE) setMethodS3("getFractionOfGenomeGained", "CBS", function(fit, ...) { stats <- getCallStatistics(fit, ...) mean(stats$gainFraction, na.rm=TRUE) }, protected=TRUE) setMethodS3("getFractionOfGenomeAltered", "CBS", function(fit, ...) { getFractionOfGenomeLost(fit, ...) + getFractionOfGenomeGained(fit, ...) }, protected=TRUE) # Shortcuts setMethodS3("getFGL", "CBS", function(fit, ...) { getFractionOfGenomeLost(fit, ...) }, protected=TRUE) setMethodS3("getFGG", "CBS", function(fit, ...) { getFractionOfGenomeGained(fit, ...) }, protected=TRUE) setMethodS3("getFGA", "CBS", function(fit, ...) { getFractionOfGenomeAltered(fit, ...) }, protected=TRUE) setMethodS3("isWholeChromosomeGained", "CBS", function(fit, minFraction=0.99, ...) { # Argument 'minFraction': minFraction <- Arguments$getDouble(minFraction, range=c(0,1)) stats <- getCallStatistics(fit, ...) calls <- stats$gainFraction if (is.null(calls)) { return(rep(NA, times=nbrOfChromosomes(fit))) } res <- (calls >= minFraction) names(res) <- stats$chromosome attr(res, "minFraction") <- minFraction res }, protected=TRUE) # isWholeChromosomeGained() setMethodS3("isWholeChromosomeLost", "CBS", function(fit, minFraction=0.99, ...) { # Argument 'minFraction': minFraction <- Arguments$getDouble(minFraction, range=c(0,1)) stats <- getCallStatistics(fit, ...) calls <- stats$lossFraction if (is.null(calls)) { return(rep(NA, times=nbrOfChromosomes(fit))) } res <- (calls >= minFraction) names(res) <- stats$chromosome attr(res, "minFraction") <- minFraction res }, protected=TRUE) # isWholeChromosomeLost() setMethodS3("nbrOfLosses", "CBS", function(fit, ...) { stats <- getSegments(fit, ...) calls <- stats$lossCall if (is.null(calls)) { return(NA_integer_) } sum(calls, na.rm=TRUE) }, protected=TRUE) setMethodS3("nbrOfGains", "CBS", function(fit, ...) { stats <- getSegments(fit, ...) calls <- stats$gainCall if (is.null(calls)) { return(NA_integer_) } sum(calls, na.rm=TRUE) }, protected=TRUE) setMethodS3("nbrOfAmplifications", "CBS", function(fit, ...) { stats <- getSegments(fit, ...) calls <- stats$amplificationCall if (is.null(calls)) { return(NA_integer_) } sum(calls, na.rm=TRUE) }, protected=TRUE) setMethodS3("getCallStatisticsByArms", "CBS", function(fit, genomeData, ...) { # To please/trick R CMD check chromosome <- x <- NULL; rm(list=c("chromosome", "x")) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'genomeData': genomeData <- as.data.frame(genomeData) # Subset 'regions' by chromosomes segmented keep <- is.element(genomeData$chromosome, getChromosomes(fit)) genomeData <- genomeData[keep,] # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # p-arm # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - regions <- getChromosomeRanges(fit) regions$end <- genomeData$centroStart regions$start <- pmin(regions$start, regions$end) # Shrink regions for (rr in seq_len(nrow(regions))) { chr <- regions[rr,"chromosome"] x0 <- regions[rr,"start"] x1 <- regions[rr,"end"] xs <- subset(fit$data, chromosome == chr & x0 <= x & x <= x1)$x if (length(xs) > 0) { range <- range(xs, na.rm=TRUE) x0 <- max(c(x0, range[1]), na.rm=TRUE) x1 <- min(c(x1, range[2]), na.rm=TRUE) regions[rr,"start"] <- x0 regions[rr,"end"] <- x1 } } # for (rr ...) regions[,"length"] <- regions[,"end"] - regions[,"start"] ## + 1L callStats <- getCallStatistics(fit, regions=regions) callStats$label <- sprintf("%sp", callStats$label) callStatsP <- callStats # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # q-arm # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - regions <- getChromosomeRanges(fit) regions$start <- genomeData$centroEnd regions$end <- pmax(regions$end, regions$start) # Shrink regions for (rr in seq_len(nrow(regions))) { chr <- regions[rr,"chromosome"] x0 <- regions[rr,"start"] x1 <- regions[rr,"end"] xs <- subset(fit$data, chromosome == chr & x0 <= x & x <= x1)$x if (length(xs) > 0) { range <- range(xs, na.rm=TRUE) x0 <- max(c(x0, range[1]), na.rm=TRUE) x1 <- min(c(x1, range[2]), na.rm=TRUE) regions[rr,"start"] <- x0 regions[rr,"end"] <- x1 } } # for (rr ...) regions[,"length"] <- regions[,"end"] - regions[,"start"] ## + 1L callStats <- getCallStatistics(fit, regions=regions) callStats$label <- sprintf("%sq", callStats$label) callStatsQ <- callStats # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Merge # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - callStats <- rbind(callStatsP, callStatsQ) # Not needed anymore regions <- callStatsP <- callStatsQ <- NULL # Reorder o <- order(callStats$chromosome, callStats$start) callStats <- callStats[o,] callStats }, protected=TRUE) # getCallStatisticsByArms() setMethodS3("callArms", "CBS", function(fit, genomeData, minFraction=0.95, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'minFraction': minFraction <- Arguments$getDouble(minFraction, range=c(0,1)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # p-arm # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - callStats <- getCallStatisticsByArms(fit, genomeData=genomeData) callTypes <- grep("Fraction", colnames(callStats), value=TRUE) callTypes <- gsub("Fraction", "", callTypes) keys <- sprintf("%sFraction", callTypes) rhos <- callStats[,keys] calls <- (rhos >= minFraction) colnames(calls) <- sprintf("%sCall", callTypes) callStats <- cbind(callStats, calls) callStats }, protected=TRUE) # callArms() ###########################################################################/** # @RdocMethod mergeNonCalledSegments # # @title "Merge neighboring segments that are not called" # # \description{ # @get "title" # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # \item{verbose}{@see "R.utils::Verbose".} # } # # \value{ # Returns an object of the same class # with the same of fewer number of segments. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("mergeNonCalledSegments", "CBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Merging neighboring segments that are not called") # Identify call columns segs <- getSegments(fit, splitters=TRUE) keep <- grep("Call$", colnames(segs)) nbrOfCalls <- length(keep) # Sanity check .stop_if_not(nbrOfCalls > 0) chromosomes <- getChromosomes(fit) fitList <- list() for (cc in seq_along(chromosomes)) { chromosome <- chromosomes[cc] verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", cc, chromosome, length(chromosomes))) fitCC <- extractChromosome(fit, chromosome=chromosome) n0 <- nbrOfSegments(fitCC) # Until no more neighboring non-called segments exists while (TRUE) { segs <- getSegments(fitCC, splitters=TRUE) calls <- as.matrix(segs[,keep]) # Find two neighboring segments that are not called isCalled <- rowAnys(calls, na.rm=TRUE, useNames=FALSE) verbose && printf(verbose, "Number of segments not called: %d of %d\n", sum(!isCalled, na.rm=TRUE), length(isCalled)) notCalled <- which(!isCalled) delta <- diff(notCalled) left <- notCalled[which(delta == 1)[1]] # No more segments to merge? if (is.na(left)) { break } fitCC <- mergeTwoSegments(fitCC, left=left) } # while (...) n1 <- nbrOfSegments(fitCC) verbose && printf(verbose, "Number of segments merged: %d of %d\n", n0-n1, n0) fitList[[cc]] <- fitCC verbose && exit(verbose) } # for (cc ...) verbose && enter(verbose, "Building result") res <- Reduce(append, fitList) verbose && exit(verbose) verbose && exit(verbose) res }, protected=TRUE) # mergeNonCalledSegments() setMethodS3("estimateDeltaCN", "CBS", function(fit, flavor=c("density(TCN)", "density(dTCN)", "dTCN"), adjust=0.3, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'adjust': adjust <- Arguments$getDouble(adjust, range=c(0,10)) if (flavor == "density(TCN)") { # Get segment mean levels segs <- getSegments(fit, splitters=FALSE) x <- segs$mean w <- segs$nbrOfLoci # Drop missing values keep <- is.finite(x) & is.finite(w) x <- x[keep] w <- w[keep] keep <- NULL # Not needed anymore # Normalize weights w <- w / sum(w, na.rm=TRUE) # Estimate density d <- density(x, weights=w, adjust=adjust) w <- NULL # Not needed anymore # Find peaks pv <- findPeaksAndValleys(d, ...) type <- NULL; rm(list="type") # To please R CMD check p <- subset(pv, type == "peak") px <- p$x pw <- p$density # Distance between peaks dx <- diff(px) # Weights "between" peaks (AD HOC: sum up peak weights) dw <- pw[-length(pw)] + pw[-1L] deltaCN <- weighted.mean(dx, w=dw) } else if (flavor == "density(dTCN)") { # Get change-point magnitudes x <- getChangePoints(fit)[[1L]] x <- abs(x) # Drop missing values keep <- is.finite(x) x <- x[keep] keep <- NULL # Not needed anymore # Estimate density d <- density(x, adjust=adjust) # Find peaks pv <- findPeaksAndValleys(d, ...) type <- NULL; rm(list="type") # To please R CMD check p <- subset(pv, type == "peak") px <- p$x pw <- p$density # Distance between peaks dx <- diff(px) # Weights "between" peaks (AD HOC: sum up peak weights) dw <- pw[-length(pw)] + pw[-1L] stop("Still not implemented.") } else if (flavor == "dTCN") { # Get change-point magnitudes x <- getChangePoints(fit)[[1L]] x <- abs(x) # Drop missing values keep <- is.finite(x) x <- x[keep] keep <- NULL # Not needed anymore deltaCN <- median(x) } # Sanity check deltaCN <- Arguments$getDouble(deltaCN, range=c(0, Inf)) deltaCN }, protected=TRUE) setMethodS3("encodeCalls", "data.frame", function(calls, flavor="UCSF", ...) { # Argument 'calls': .stop_if_not(all(is.element(c("chromosome", "x"), colnames(calls)))) .stop_if_not(all(is.element(c("lossCall", "gainCall"), colnames(calls)))) # Argument 'flavor': flavor <- match.arg(flavor) calls0 <- calls # Allocate calls <- rep(NA_real_, times=nrow(calls0)) # Encode loss, neutral and gain (required) calls[!calls0$gainCall & !calls0$lossCall] <- 0 calls[calls0$gainCall] <- +1 calls[calls0$lossCall] <- -1 # Encode amplifications, if any/called. idxs <- which(calls0$amplificationCall) calls[idxs] <- +9 # Encode negative and positive outliers, if any/called. idxs <- which(calls0$negOutlierCall) calls[idxs] <- calls[idxs] - 0.1 idxs <- which(calls0$posOutlierCall) calls[idxs] <- calls[idxs] + 0.1 calls }, protected=TRUE) # encodeCalls() setMethodS3("callGLAO", "CBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Call gains, losses, amplifications and (negative and positive) outliers") verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fit)) # Call segments fitC <- callGainsAndLosses(fit, ..., verbose=verbose) fitC <- callAmplifications(fitC, ..., verbose=verbose) # Call loci, i.e. locus-level negative and positive outliers fitC <- callOutliers(fitC, ..., verbose=verbose) verbose && print(verbose, fitC) verbose && exit(verbose) fitC }, protected=TRUE) # callGLAO() PSCBS/R/PairedPSCBS.applyByRegion.R0000644000176200001440000001764414564051545016257 0ustar liggesuserssetMethodS3("applyByRegion", "PairedPSCBS", function(fit, FUN, ..., subset=NULL, append=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'FUN': .stop_if_not(is.function(FUN)) # Argument 'subset': if (!is.null(subset)) { subset <- Arguments$getIndices(subset, range=c(1, nbrOfSegments(fit))) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Apply function region by region") verbose && cat(verbose, "Segments:") verbose && str(verbose, subset) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit) tcnSegRows <- fit$tcnSegRows dhSegRows <- fit$dhSegRows params <- fit$params # Sanity checks if (!params$joinSegments) { stop("Cannot applyByRegion() unless PSCNs are segmented using joinSegments=TRUE.") } dataRows <- tcnSegRows # Sanity checks .stop_if_not(all(!is.na(data$chromosome) & !is.na(data$x))) .stop_if_not(length(tcnSegRows) == length(dhSegRows)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each segment... # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments) # Allocate result objects? if (append) { dataN <- outputN <- dataRowsN <- NULL } if (is.null(subset)) { subset <- seq_len(nbrOfSegments) } for (rr in subset) { verbose && enter(verbose, sprintf("Segment #%d of %d", rr, nbrOfSegments)) # Extract segment segRR <- segs[rr,,drop=FALSE] # Nothing todo? if (is.na(segRR[["tcnId"]]) && is.na(segRR[["dhId"]])) { verbose && cat(verbose, "A divider. Nothing to do.") outputN <- rbind(outputN, NA) dataRowsN <- rbind(dataRowsN, NA) verbose && exit(verbose) next } verbose && str(verbose, segRR, level=-20) # Extract data dataRowsRR <- dataRows[rr,,drop=FALSE] from <- dataRowsRR[[1]] to <- dataRowsRR[[2]] ok <- (!is.na(from) & !is.na(to)) from <- from[ok] to <- to[ok] keep <- logical(nrow(data)) for (kk in seq_along(from)) { keep[from[kk]:to[kk]] <- TRUE } dataRowsRR <- which(keep) verbose && printf(verbose, "Identified %d (%.2f%%) of %d data rows:\n", length(dataRowsRR), 100*length(dataRowsRR)/nrow(data), nrow(data)) verbose && str(verbose, dataRowsRR) dataRR <- data[dataRowsRR,,drop=FALSE] verbose && str(verbose, dataRR, level=-20) verbose && enter(verbose, "Applying function 'FUN' to segment") resRR <- FUN(rr, segRR, dataRR, ...) verbose && cat(verbose, "Returned result:") verbose && str(verbose, resRR, level=-20) verbose && exit(verbose) # Nothing to update/store? if (!is.list(resRR)) { verbose && cat(verbose, "Nothing more to do for this segment since nothing was returned: ", rr) verbose && exit(verbose) next } # Extract return data dataRRN <- resRR$data segRRN <- resRR$output # Sanity check .stop_if_not(!is.null(dataRRN)) .stop_if_not(is.data.frame(dataRRN)) .stop_if_not(!is.null(segRRN)) .stop_if_not(is.data.frame(segRRN)) if (append) { # Modified locus-level data dataRowsRRN <- c(1L, nrow(dataRRN)) if (!is.null(dataN)) { dataRowsRRN <- dataRowsRRN + nrow(dataN) } dataN <- rbind(dataN, dataRRN) # Sanity checks .stop_if_not(nrow(dataN) == max(dataRowsN, na.rm=TRUE)) # Update segment table? outputN <- rbind(outputN, segRRN) dataRowsN <- rbind(dataRowsN, dataRowsRRN) # Sanity check .stop_if_not(nrow(outputN) == nrow(dataRowsN)) # Sanity checks .stop_if_not(nrow(dataN) == max(dataRowsN, na.rm=TRUE)) } else { # Modified locus-level data verbose && enter(verbose, "Updating locus-level data") # Sanity check .stop_if_not(dim(dataRRN) == dim(dataRR)) .stop_if_not(length(dataRowsRR) == nrow(dataRRN)) data[dataRowsRR,] <- dataRRN str(data[dataRowsRR,]) verbose && exit(verbose) # Modified segment data verbose && enter(verbose, "Updating segment data") # Sanity check .stop_if_not(dim(segRRN) == dim(segRR)) segs[rr,] <- segRRN verbose && exit(verbose) } # Not needed anymore dataRRN <- segRRN <- NULL dataRR <- segRR <- NULL resRR <- NULL verbose && exit(verbose) } # for (rr ...) if (append) { if (!is.null(dataRowsN)) { rownames(dataRowsN) <- NULL colnames(dataRowsN) <- colnames(dataRows) dataRowsN <- as.data.frame(dataRowsN) # Sanity checks .stop_if_not(!is.null(dataN)) .stop_if_not(!is.null(outputN)) .stop_if_not(!is.null(dataRowsN)) data <- dataN segs <- outputN # Not needed anymore dataN <- outputN <- NULL } } # Return result res <- fit # "clone" res$data <- data res$output <- segs # Not needed anymore data <- segs <- NULL # Update segment-to-locus index tables if (append && !is.null(dataRowsN)) { res$tcnSegRows <- dataRowsN res$dhSegRows <- dataRowsN # Is this really the case? /HB 2011-01-17 } verbose && exit(verbose) res }, private=TRUE) .addC1C2WithStatitics <- function(rr, output, data, robust=TRUE, ...) { # Calculate locus-level (C1,C2) C <- data$CT rho <- data$rho C1 <- 1/2 * (1 - rho) * C C2 <- C - C1 CC <- data.frame(C1=C1, C2=C2) if (robust) { meanFcn <- function(x, ...) median(x, na.rm=TRUE) sdFcn <- function(x, ...) mad(x, na.rm=TRUE) } else { meanFcn <- function(x, ...) mean(x, na.rm=TRUE) sdFcn <- function(x, ...) sd(x, na.rm=TRUE) } # Calculate region-level (C1,C2) means and std devs. muCC <- apply(CC, MARGIN=2, FUN=meanFcn) sigmaCC <- apply(CC, MARGIN=2, FUN=sdFcn) rhoCC <- cor(CC[,1], CC[,2], use="pairwise.complete.obs") names(muCC) <- c("c1Avg", "c2Avg") names(sigmaCC) <- c("c1Sd", "c2Sd") # Update data data <- cbind(data, CC) # Update segment table outputT <- c(muCC, sigmaCC, c1c2.cor=rhoCC) outputT <- as.list(outputT) outputT <- as.data.frame(outputT) output <- cbind(output, outputT) list(data=data, output=output) } # .addC1C2WithStatitics() .addCACBWithStatitics <- function(rr, output, data, beta=c("betaTN", "betaT"), stratifyBy=c("all", "hets", "homs"), robust=TRUE, ...) { # Argument 'beta': beta <- match.arg(beta) # Argument 'stratifyBy': stratifyBy <- match.arg(stratifyBy) # Calculate locus-level (CA,CB) C <- data$CT beta <- data[[beta]] CB <- beta * C CA <- C - CB CC <- data.frame(CA=CA, CB=CB) # Update data data <- cbind(data, CC) if (robust) { meanFcn <- function(x, ...) median(x, na.rm=TRUE) sdFcn <- function(x, ...) mad(x, na.rm=TRUE) } else { meanFcn <- function(x, ...) mean(x, na.rm=TRUE) sdFcn <- function(x, ...) sd(x, na.rm=TRUE) } if (stratifyBy == "hets") { muN <- data$muN keep <- (muN == 1/2) CC <- CC[keep,,drop=FALSE] } else if (stratifyBy == "homs") { muN <- data$muN keep <- (muN == 0 | muN == 1) CC <- CC[keep,,drop=FALSE] } # Calculate region-level (CA,CB) means and std devs. muCC <- apply(CC, MARGIN=2, FUN=meanFcn) sigmaCC <- apply(CC, MARGIN=2, FUN=sdFcn) if (nrow(CC) < 3) { rhoCC <- NA_real_ } else { rhoCC <- cor(CC[,1], CC[,2], use="pairwise.complete.obs") } names(muCC) <- c("caAvg", "cbAvg") names(sigmaCC) <- c("caSd", "cbSd") # Update segment table outputT <- c(muCC, sigmaCC, cacbCor=rhoCC) outputT <- as.list(outputT) outputT <- as.data.frame(outputT) output <- cbind(output, outputT) list(data=data, output=output) } # .addCACBWithStatitics() PSCBS/R/AbstractCBS.HCLUST.R0000644000176200001440000001532114564202700014546 0ustar liggesusers###########################################################################/** # @set "class=AbstractCBS" # @RdocMethod updateMeansTogether # @alias updateMeansTogether.CBS # @alias updateMeansTogether.PairedPSCBS # # @title "Updates the CN mean levels jointly in sets of segments" # # \description{ # @get "title" as if they were one large segment. # The locus-level data is not updated/modified. # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns an object of the same class. # } # # @author "HB" # # \seealso{ # This method is utilized by @seemethod "pruneByHClust". # } # # @keyword internal #*/########################################################################### setMethodS3("updateMeansTogether", "AbstractCBS", abstract=TRUE, private=TRUE) ###########################################################################/** # @set "class=AbstractCBS" # @RdocMethod hclustCNs # # @title "Performs a hierarchical clustering of the CN mean levels" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{size}{Argument passed to @seemethod "sampleCNs".} # \item{distMethod, hclustMethod}{Argument \code{method} for # @see "stats::dist" and "stats::hclust", respectively.} # \item{...}{Not used.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a \code{hclust} object as returned by @see "stats::hclust". # } # # @author # # \seealso{ # This method is utilized by @seemethod "pruneByHClust". # } # # @keyword internal #*/########################################################################### setMethodS3("hclustCNs", "AbstractCBS", function(fit, size=NULL, distMethod="euclidean", hclustMethod="ward.D", ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Hierarchical clustering of segmented copy numbers") verbose && enter(verbose, "Extracting/sampling CNs") C <- sampleCNs(fit, size=size, splitters=FALSE) verbose && str(verbose, C) # Drop also segments with no data points ok <- !is.na(C) ok <- rowAlls(ok, useNames=FALSE) C <- C[ok,,drop=FALSE] verbose && str(verbose, C) verbose && exit(verbose) verbose && enter(verbose, "Calculating distance matrix") D <- stats::dist(C, method=distMethod) verbose && str(verbose, D) verbose && exit(verbose) verbose && enter(verbose, "Clustering") # TODO: Do *weighted* hierarchical clustering tree <- stats::hclust(D, method=hclustMethod) verbose && str(verbose, tree) verbose && exit(verbose) verbose && exit(verbose) tree }, private=TRUE) # hclustCNs() ###########################################################################/** # @RdocMethod pruneByHClust # # @title "Prunes the CN profile by pruning and merging through hierarchical clustering" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to @see "stats::cutree", # particularly either of thresholds \code{h} or \code{k}.} # \item{size, distMethod, hclustMethod}{Arguments (as well as # some of \code{...}) passed to @seemethod "hclustCNs".} # \item{merge}{If @TRUE, consecutive segments that belong to the # same PSCN cluster will be merged into one large segment.} # \item{update}{If @TRUE, segment means are updated afterwards, otherwise not.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a pruned object of the same class. # } # # \examples{\dontrun{ # fitP <- pruneByHClust(fit, h=0.25) # }} # # @author # # @keyword internal #*/########################################################################### setMethodS3("pruneByHClust", "AbstractCBS", function(fit, ..., size=NULL, distMethod="euclidean", hclustMethod="ward.D", merge=TRUE, update=TRUE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Prune segments by hierarchical clustering") verbose && cat(verbose, "Clustering arguments:") verbose && str(verbose, c(list(size=size, distMethod=distMethod, hclustMethod=hclustMethod), list(...))) verbose && enter(verbose, "Clustering") tree <- hclustCNs(fit, size=size, distMethod=distMethod, hclustMethod=hclustMethod, ..., verbose=less(verbose,5)) verbose && print(verbose, tree) verbose && exit(verbose) verbose && enter(verbose, "Cutting tree") verbose && cat(verbose, "Cutting arguments:") verbose && str(verbose, c(list(tree=tree), list(...))) p <- cutree(tree, ...) verbose && str(verbose, p) # Group segments idxList <- by(names(p), p, FUN=function(x) { idxs <- as.integer(as.character(x)) idxs <- sort(unique(idxs)) list(idxs) }) verbose && str(verbose, idxList) verbose && exit(verbose) # Dropping previous segment calls and quantile mean-level estimates. fit <- resetSegments(fit) verbose && enter(verbose, "Merging mean levels of clustered segments") fit <- updateMeansTogether(fit, idxList=idxList, verbose=less(verbose, 10)) verbose && exit(verbose) if (merge) { verbose && enter(verbose, "Merging neighboring segments within each cluster") lefts <- c() for (ii in seq_along(idxList)) { verbose && enter(verbose, sprintf("Cluster #%d of %d", ii, length(idxList))) idxs <- idxList[[ii]] verbose && cat(verbose, "Segments in cluster:") verbose && str(verbose, idxs) # Indices to segments to merge leftsII <- idxs[which(diff(idxs) == 1L)] verbose && cat(verbose, "Left indices of neighboring segments:") verbose && str(verbose, leftsII) lefts <- c(lefts, leftsII) verbose && exit(verbose) } # for (ii ...) lefts <- sort(unique(lefts)) verbose && cat(verbose, "Left indices of segments to be merged:") verbose && str(verbose, lefts) verbose && exit(verbose) verbose && enter(verbose, "Merging segments") lefts <- rev(lefts) for (ii in seq_along(lefts)) { fit <- mergeTwoSegments(fit, left=lefts[ii], update=FALSE) } # for (ii ...) verbose && exit(verbose) } # if (merge) if (update) { verbose && enter(verbose, "Updating segment means") ## fit <- updateBoundaries(fit, verbose=less(verbose, 50)) fit <- updateMeans(fit, verbose=less(verbose, 50)) verbose && exit(verbose) } verbose && exit(verbose) fit }, protected=TRUE) # pruneByHClust() PSCBS/R/PSCBS.IO.R0000644000176200001440000001105114564051545012637 0ustar liggesusers###########################################################################/** # @set "class=PSCBS" # @RdocMethod writeSegments # # @title "Writes the table of segments to file" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{name, tags}{Name and optional tags part of the filename}. # \item{path}{The directory where the file will be written.} # \item{addHeader}{If @TRUE, header comments are written.} # \item{createdBy}{A header comment of whom created the file.} # \item{splitters}{If @TRUE, each chromosome is separated by a row # of missing values.} # \item{overwrite, skip}{If an output file already exists, these # arguments specifies what should happen.} # \item{...}{Additional arguments pass to \code{getSegments()}.} # } # # \value{ # Returns the pathname of the the file written. # } # # @author "HB" # # \seealso{ # Utilizes @seemethod "getSegments". # @seeclass. # } # # @keyword internal #*/########################################################################### setMethodS3("writeSegments", "PSCBS", function(fit, name=getSampleName(fit), tags=NULL, ext="tsv", path=NULL, addHeader=TRUE, createdBy=NULL, sep="\t", nbrOfDecimals=4L, splitters=FALSE, overwrite=FALSE, skip=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'name' and 'tags': name <- Arguments$getCharacter(name) tags <- Arguments$getCharacters(tags) # Argument 'ext': ext <- Arguments$getCharacter(ext) # Arguments 'path': path <- Arguments$getWritablePath(path) # Argument 'nbrOfDecimals': nbrOfDecimals <- Arguments$getInteger(nbrOfDecimals) fullname <- paste(c(name, tags), collapse=",") filename <- sprintf("%s.%s", fullname, ext) pathname <- Arguments$getWritablePathname(filename, path=path, mustNotExist=(!overwrite && !skip)) # File already exists? if (isFile(pathname)) { # Skip? if (skip) { return(pathname) } # Overwrite! file.remove(pathname) } # Write to temporary file pathnameT <- pushTemporaryFile(pathname) sampleName <- getSampleName(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getSegments(fit, ..., splitters=splitters) # Round of floating points if (!is.null(nbrOfDecimals)) { cols <- tolower(colnames(data)) isInt <- (regexpr("chromosome|start|end|nbrofloci", cols) != -1) cols <- which(isInt) for (cc in cols) { values <- data[[cc]] if (is.double(values)) { values <- round(values, digits=0) data[[cc]] <- values } } # for (key ...) cols <- tolower(colnames(data)) isInt <- (regexpr("chromosome|start|end|nbrofloci", cols) != -1) isLog <- (regexpr("call", cols) != -1) isDbl <- (!isInt & !isLog) cols <- which(isDbl) for (kk in cols) { values <- data[[kk]] if (is.double(values)) { values <- round(values, digits=nbrOfDecimals) data[[kk]] <- values } } # for (key ...) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Build header # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (addHeader) { # sigmaDelta <- estimateStandardDeviation(fit, method="diff") sigmaDelta <- NA # sigmaResiduals <- estimateStandardDeviation(fit, method="res") createdOn <- format(Sys.time(), format="%Y-%m-%d %H:%M:%S %Z") hdr <- c( name=name, tags=tags, fullname=fullname, segmentationMethod=sprintf("segment() of %s", attr(fit, "pkgDetails")), nbrOfLoci=nbrOfLoci(fit), nbrOfSegments=nbrOfSegments(fit), joinSegments=fit$params$joinSegments, # signalType=getSignalType(fit), sigmaDelta=sprintf("%.4f", sigmaDelta), # sigmaResiduals=sprintf("%.4f", sigmaResiduals), createdBy=createdBy, createdOn=createdOn, nbrOfDecimals=nbrOfDecimals, nbrOfColumns=ncol(data), columnNames=paste(colnames(data), collapse=", "), columnClasses=paste(sapply(data, FUN=function(x) class(x)[1]), collapse=", ") ) bfr <- paste("# ", names(hdr), ": ", hdr, sep="") cat(file=pathnameT, bfr, sep="\n") } # if (addHeader) write.table(file=pathnameT, data, append=TRUE, quote=FALSE, sep=sep, row.names=FALSE, col.names=TRUE) pathname <- popTemporaryFile(pathnameT) pathname }) # writeSegments() PSCBS/R/000.R0000644000176200001440000000031314564051545011755 0ustar liggesusers## Look for existing generic functions also in imported namespaces. ## This will affect whether setGenericS3() creates a generic function ## or not. options("R.methodsS3:checkImports:setGenericS3"=TRUE) PSCBS/R/PSCBS.R0000644000176200001440000001357414564051545012345 0ustar liggesusers###########################################################################/** # @RdocClass PSCBS # # @title "The PSCBS class" # # \description{ # @classhierarchy # # A PSCBS is an object containing results from parent-specific copy-number # (PSCN) segmentation. # } # # \usage{PSCBS(fit=list(), ...)} # # \arguments{ # \item{fit}{A @list structure containing the PSCN segmentation results.} # \item{...}{Not used.} # } # # \section{Fields and Methods}{ # @allmethods "public" # } # # @author "HB" # # \seealso{ # @see "PairedPSCBS". # } #*/########################################################################### setConstructorS3("PSCBS", function(fit=list(), ...) { # Argument 'fit': if (!is.list(fit)) { stop("Argument 'fit' is not a list: ", class(fit)[1]) } extend(AbstractCBS(fit, ...), "PSCBS") }) setMethodS3("as.data.frame", "PSCBS", function(x, ...) { getSegments(x, splitters=TRUE, ...) }, protected=TRUE) setMethodS3("getLocusSignalNames", "PSCBS", function(fit, ...) { c("CT", "rho") }, protected=TRUE) setMethodS3("getSegmentTrackPrefixes", "PSCBS", function(fit, ...) { c("tcn", "dh") }, protected=TRUE) setMethodS3("getLocusData", "PSCBS", function(fit, indices=NULL, fields=c("asis"), ...) { # Argument 'indices': if (!is.null(indices)) { indices <- Arguments$getIndices(indices) } # Argument 'fields': fields <- match.arg(fields) data <- fit$data # Return requested indices if (!is.null(indices)) { # Map of final indices to current indices map <- match(indices, data$index) # Extract/expand... data <- data[map,] # Sanity check .stop_if_not(nrow(data) == length(indices)) } data }, protected=TRUE) # getLocusData() setMethodS3("isSegmentSplitter", "PSCBS", function(fit, ...) { segs <- fit$output isSplitter <- lapply(segs[-1], FUN=is.na) isSplitter <- Reduce("&", isSplitter) isSplitter }, protected=TRUE) ###########################################################################/** # @RdocMethod getSegments # # @title "Gets the segments" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{simplify}{If @TRUE, redundant and intermediate information is dropped.}# \item{splitters}{If @TRUE, "splitters" between chromosomes are # preserved, otherwise dropped.} # \item{...}{Not used.} # } # # \value{ # Returns a SxK @data.frame, where S in the number of segments, # and K is the number of segment-specific fields. # } # # @author "HB" # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("getSegments", "PSCBS", function(fit, simplify=FALSE, splitters=TRUE, addGaps=FALSE, ...) { # Argument 'splitters': splitters <- Arguments$getLogical(splitters) segs <- fit$output # Drop chromosome splitters? if (!splitters) { isSplitter <- isSegmentSplitter(fit) segs <- segs[!isSplitter,] } # Add splitters for "gaps"... if (splitters && addGaps) { # Chromosome gaps n <- nrow(segs) chrs <- segs$chromosome gapsAfter <- which(diff(chrs) != 0L) gapsAfter <- gapsAfter[!is.na(chrs[gapsAfter])] nGaps <- length(gapsAfter) if (nGaps > 0L) { idxs <- seq_len(n) values <- rep(NA_integer_, times=nGaps) idxs <- insert(idxs, ats=gapsAfter+1L, values=values) segs <- segs[idxs,] } # Other gaps n <- nrow(segs) chrs <- segs$chromosome starts <- segs$tcnStart[-1L] ends <- segs$tcnEnd[-n] gapsAfter <- which(starts != ends) onSameChr <- (chrs[gapsAfter+1L] == chrs[gapsAfter] ) gapsAfter <- gapsAfter[onSameChr] nGaps <- length(gapsAfter) if (nGaps > 0L) { idxs <- seq_len(n) values <- rep(NA_integer_, times=nGaps) idxs <- insert(idxs, ats=gapsAfter+1L, values=values) segs <- segs[idxs,] } } ## if (nrow(segs) > 0) { ## segs$id <- getSampleName(fit) ## } if (simplify) { # If joinSegments was used (i.e. (start,end) are equal for TCN and DH)... if (fit$params$joinSegments) { # Sanity check .stop_if_not(all(segs$tcnStart == segs$dhStart, na.rm=TRUE)) .stop_if_not(all(segs$tcnEnd == segs$dhEnd, na.rm=TRUE)) names <- colnames(segs) keep <- !is.element(names, c("dhStart", "dhEnd")) segs <- segs[,keep] names <- colnames(segs) names[names == "tcnStart"] <- "start" names[names == "tcnEnd"] <- "end" colnames(segs) <- names } # Drop bootstrap columns, if any names <- colnames(segs) keep <- (regexpr("_[0-9]+(|[.][0-9]+)%$", names) == -1) segs <- segs[,keep] } segs }, private=TRUE) setMethodS3("getChangePoints", "PSCBS", function(fit, ...) { # Already available? cps <- fit$changepoints if (!is.null(cps)) return(cps) segs <- getSegments(fit, splitters=TRUE) tcn <- segs[["tcnMean"]] dh <- segs[["dhMean"]] C1 <- (1-dh) * tcn / 2 C2 <- tcn - C1 n <- length(tcn) # Calculate observed (alpha, radius, manhattan, dc1, dc2) data D1 <- C1[-n] - C1[-1L] D2 <- C2[-n] - C2[-1L] cps <- data.frame( alpha = atan2(D2, D1), # Changepoint angles in (0,2*pi) radius = sqrt(D2^2 + D1^2), manhattan = abs(D2) + abs(D1), d1 = D1, d2 = D2 ) cps }, private=TRUE) # getChangePoints() setMethodS3("normalizeTotalCNs", "PSCBS", function(fit, targetTCN=2, ...) { ## Fit using locus-level data data <- getLocusData(fit, ...) C <- data$CT .stop_if_not(!is.null(C)) mu <- median(C, na.rm=TRUE) scale <- targetTCN / mu ## (a) Rescale locus-level data C <- scale * C data$CT <- C rm(list="C") fitN <- setLocusData(fit, data) ## (b) Rescale segment-level data segs <- getSegments(fit) fields <- colnames(segs) cnFields <- grep("^(tcn|c1|c2)", fields, value=TRUE) cnFields <- grep("(Id|Start|End|NbrOf)", cnFields, value=TRUE, invert=TRUE) for (field in cnFields) { segs[[field]] <- scale * segs[[field]] } fitN <- setSegments(fitN, segs) invisible(fitN) }) PSCBS/R/randomSeed.R0000644000176200001440000000635014564051545013546 0ustar liggesusers###########################################################################/** # @RdocFunction randomSeed # # @title "Sets and resets the .Random.seed in the global environment" # # \description{ # @get "title". # } # # \usage{ # @usage randomSeed # } # # \arguments{ # \item{action}{A @character string specifying the action.} # \item{seed}{Random seed to be set; only for \code{action="set"}. # If \code{length(seed) == 1}, then \code{set.seed(seed)} is # used, otherwise \code{.Random.seed} is assigned the value.} # \item{kind}{(optional) A @character string specifying type of # random number generator to use, cf. @see "base::RNGkind".} # \item{n}{Number of random seeds to generate by \code{action}.} # \item{backup}{If @TRUE, the previous (seed, kind) state is recorded # such that it can be reset later.} # } # # \value{ # Returns a \code{.Random.seed}. # If more than one is returned, the they are returned as a @list. # } # # @author "HB" # # @keyword internal #*/########################################################################### randomSeed <- local({ oldSeed <- NULL oldKind <- NULL lecuyerSeed <- NULL genv <- globalenv() getSeed <- function() { if (exists(".Random.seed", envir=genv, inherits=FALSE)) { get(".Random.seed", envir=genv, inherits=FALSE) } else { NULL } } setSeed <- function(seed, kind=NULL, backup=TRUE) { force(seed) ## FIX: Why is this needed? ## Set new RNG kind? newKind <- (!is.null(kind) && !identical(kind, RNGkind()[1L])) if (newKind) { if (backup) { oldSeed <<- getSeed() oldKind <<- RNGkind()[1L] } RNGkind(kind) ## Sets .Random.seed } ## Reset or set seed? if (is.null(seed)) { if (exists(".Random.seed", envir=genv, inherits=FALSE)) { rm(list=".Random.seed", envir=genv, inherits=FALSE) lecuyerSeed <<- NULL } } else { if (backup && !newKind) oldSeed <<- getSeed() if (length(seed) == 1L) { set.seed(seed) lecuyerSeed <<- getSeed() } else { assign(".Random.seed", seed, envir=genv, inherits=FALSE) lecuyerSeed <<- seed } } } advanceSeed <- function() { ## Nothing to do? if (RNGkind()[1L] != "L'Ecuyer-CMRG") return() if (is.null(lecuyerSeed)) { stats::runif(1) lecuyerSeed <<- getSeed() } lecuyerSeed <<- nextRNGStream(lecuyerSeed) assign(".Random.seed", lecuyerSeed, envir=genv, inherits=FALSE) } function(action=c("set", "advance", "reset", "get"), seed=NULL, kind=NULL, n=1L, backup=TRUE) { action <- match.arg(action) n <- as.integer(n) .stop_if_not(n >= 1) ## Record existing RNG kind (only once) if (is.null(oldKind)) oldKind <<- RNGkind()[1L] if (action == "set") { setSeed(seed=seed, kind=kind, backup=backup) } else if (action == "advance") { seeds <- list() for (kk in seq_len(n)) { advanceSeed() seeds[[kk]] <- getSeed() } if (n == 1) seeds <- seeds[[1]] return(seeds) } else if (action == "reset") { setSeed(seed=oldSeed, kind=oldKind, backup=FALSE) } else if (action == "get") { return(getSeed()) } invisible(getSeed()) } }) # randomSeed() PSCBS/R/CBS.PRUNE.R0000644000176200001440000001606414564051545012767 0ustar liggesusers###########################################################################/** # @set "class=CBS" # @RdocMethod pruneBySdUndo # # @title "Prune the CBS profile by dropping change points that are too small" # # \description{ # @get "title", where "too small" means that the amplitude of the # change points is less than a multiple of the overall standard deviation # of the copy-number signals. # } # # @synopsis # # \arguments{ # \item{fit}{A @see "CBS" object.} # \item{rho}{A positive @double scalar specifying the number of standard # deviations (\code{rho*sigma}) required in order to keep a change point. # More change points are dropped the greater this value is.} # \item{sigma}{The whole-genome standard deviation of the locus-level # copy number signals. The default is to calculate it from the data # and as done in the \pkg{DNAcopy} package.} # \item{...}{(Optional) Additional arguments passed to the standard # deviation estimator function.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a @see "CBS" object (of the same class as \code{fit}). # } # # \details{ # This method corresponds to using the \code{undo} argument when calling # @see "segmentByCBS", which in turn corresponds to using the # \code{undo.splits="sdundo"} and \code{undo.SD} of the underlying # @see "DNAcopy::segment" method. # } # # @examples "../incl/segmentByCBS,pruneBySdUndo.Rex" # # @author "HB, PN" # # @keyword internal #*/########################################################################### setMethodS3("pruneBySdUndo", "CBS", function(fit, rho=3, sigma="DNAcopy", ..., verbose=FALSE) { # Local copies of DNAcopy functions DNAcopy_changepoints.sdundo <- .use("changepoints.sdundo", package="DNAcopy") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'rho': rho <- Arguments$getDouble(rho, range=c(0,Inf)) # Argument 'sigma': if (is.character(sigma)) { sigma <- estimateStandardDeviation(fit, method=sigma, ...) } sigma <- Arguments$getDouble(sigma, range=c(0,Inf), disallow=c("NA", "NaN", "Inf")) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Pruning segments by standard deviation") # Check if locus weights are available data <- getLocusData(fit) hasWeights <- !is.null(data$w) # Not needed anymore data <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Prune chromosome by chromosome # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chromosomes <- getChromosomes(fit) nbrOfChromosomes <- length(chromosomes) fitList <- vector("list", length=nbrOfChromosomes) for (cc in seq_len(nbrOfChromosomes)) { chr <- chromosomes[cc] verbose && enter(verbose, sprintf("Chromosome #%d ('Chr%s') of %d", cc, chr, length(chromosomes))) # Extract this chromosome fitT <- extractChromosome(fit, chromosome=chr) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get segmentation data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fitT) segs <- getSegments(fitT) segRows <- fitT$segRows nbrOfSegs <- nrow(segRows) verbose && cat(verbose, "Number of segments (before): ", nbrOfSegs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop missing values # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - y <- data$y # Label data points by their segment index segId <- rep(NA_integer_, times=max(segRows[,2], na.rm=TRUE)) for (rr in 1:nbrOfSegs) { segRow <- unlist(segRows[rr,], use.names=FALSE) idxs <- segRow[1]:segRow[2] segId[idxs] <- rr } # Drop missing value keep <- !is.na(y) if (hasWeights) { w <- data$w keep <- keep & !is.na(w) } units <- which(keep) y <- y[units] segId <- segId[units] if (hasWeights) { w <- w[units] } # Update 'segRows' accordingly for (rr in 1:nbrOfSegs) { startStop <- range(which(segId == rr)) segRows[rr,1] <- startStop[1] segRows[rr,2] <- startStop[2] } # Not needed anymore segId <- startStop <- NULL # Sanity check .stop_if_not(max(segRows[,2]) <= length(y)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Prune change points # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segLengths <- segRows[,2] - segRows[,1] + 1L segLengthsP <- DNAcopy_changepoints.sdundo(genomdat=y, lseg=segLengths, trimmed.SD=sigma, change.SD=rho) segLengthsP <- as.integer(segLengthsP) nbrOfSegsP <- length(segLengthsP) verbose && cat(verbose, "Number of segments (after): ", nbrOfSegsP) nbrOfPrunedSegs <- nbrOfSegs-nbrOfSegsP verbose && cat(verbose, "Number of segments dropped: ", nbrOfPrunedSegs) # No segments pruned? if (nbrOfPrunedSegs == 0) { # Sanity check .stop_if_not(identical(segLengthsP, segLengths)) fitList[[cc]] <- fitT verbose && cat(verbose, "Nothing to changed. Skipping.") # verbose && exit(verbose) # next } # Setup new 'segRows' endRow <- cumsum(segLengthsP) n <- length(endRow) segRowsP <- data.frame(startRow=c(1L, endRow[-n]+1L), endRow=endRow) # Expand to units with also missing values segRowsP[,1] <- units[segRowsP[,1]] segRowsP[,2] <- units[segRowsP[,2]] # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Create stub for a segment table # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - idxs <- seq_len(nbrOfSegsP) segsP <- segs[idxs,] # Sanity checks if (nbrOfPrunedSegs == 0) { segRows <- fitT$segRows .stop_if_not(all.equal(segRowsP, segRows, check.attributes=FALSE)) .stop_if_not(all.equal(segsP, segs, check.attributes=FALSE)) } fitT$output <- segsP fitT$segRows <- segRowsP fitList[[cc]] <- fitT verbose && exit(verbose) } # for (cc ...) ## formerly Reduce() w/ append(..., addSplit = TRUE) fitP <- do.call(c, args = c(fitList, addSplit = TRUE)) verbose && enter(verbose, "Updating segment means and boundaries") fitP <- updateBoundaries(fitP, verbose=less(verbose, 50)) fitP <- updateMeans(fitP, verbose=less(verbose, 50)) verbose && exit(verbose) nbrOfSegs <- nbrOfSegments(fit) nbrOfSegsP <- nbrOfSegments(fitP) nbrOfPrunedSegs <- nbrOfSegs-nbrOfSegsP verbose && cat(verbose, "Number of segments (before): ", nbrOfSegs) verbose && cat(verbose, "Number of segments (after): ", nbrOfSegsP) verbose && cat(verbose, "Number of segments dropped: ", nbrOfPrunedSegs) verbose && exit(verbose) fitP }) # pruneBySdUndo() setMethodS3("seqOfSegmentsByDP", "CBS", function(fit, by=c("y"), ...) { NextMethod("seqOfSegmentsByDP", by=by) }) PSCBS/R/PSCBS.isLocallyPhased.R0000644000176200001440000000056114564051545015414 0ustar liggesuserssetMethodS3("isLocallyPhased", "PSCBS", function(fit, ...) { segs <- getSegments(fit) is.element("c1c2Swap", names(segs)) }) ############################################################################## # HISTORY # 2014-03-24 [HB] # o Added isLocallyPhased() for PSCBS. # o Created. ############################################################################## PSCBS/R/PairedPSCBS.R0000644000176200001440000001705014564051545013463 0ustar liggesusers###########################################################################/** # @RdocClass PairedPSCBS # # @title "The PairedPSCBS class" # # \description{ # @classhierarchy # # A PairedPSCBS is an object containing the results from the # Paired PSCBS method. # } # # \usage{PairedPSCBS(fit=list(), ...)} # # \arguments{ # \item{fit}{A @list structure containing the Paired PSCBS results.} # \item{...}{Not used.} # } # # \section{Fields and Methods}{ # @allmethods "public" # } # # @author "HB" # # \seealso{ # The @see "segmentByPairedPSCBS" method returns an object of this class. # } #*/########################################################################### setConstructorS3("PairedPSCBS", function(fit=list(), ...) { # Argument 'fit': if (!is.list(fit)) { stop("Argument 'fit' is not a list: ", class(fit)[1]) } extend(PSCBS(fit=fit, ...), "PairedPSCBS") }) setMethodS3("getLocusData", "PairedPSCBS", function(fit, ..., fields=c("asis", "full")) { # Argument 'fields': fields <- match.arg(fields) data <- NextMethod("getLocusData", fields="asis") if (fields == "full") { names <- colnames(data) # Genotype calls if (!is.element("muN", names)) { if (is.element("rho", names)) { data$muN <- rep(NA_real_, times=length(data$rho)) data$muN[is.finite(data$rho)] <- 1/2 } else if (is.element("betaN", names)) { data$muN <- callNaiveGenotypes(data$betaN) } else { stop("Cannot identify heterozygous SNPs or genotypes") } } data$isHet <- (data$muN == 1/2) # BACKWARD COMPATIBILITY: If 'rho' does not exists, calculate # it on the fly from 'betaT'. # NOTE: This should give an error in the future. /HB 2013-10-25 if (is.null(data$rho)) { data$rho <- 2*abs(data$betaT-1/2) data$rho[!data$isHet] <- NA_real_ warning("Locus-level DH signals ('rho') did not exist and were calculated from tumor BAFs ('betaT')") } data$c1 <- 1/2*(1-data$rho)*data$CT data$c2 <- data$CT - data$c1 # TumorBoost BAFs if (!is.element("rhoN", names)) { if (!is.element("betaTN", names) && is.element("betaN", names)) { data$betaTN <- normalizeTumorBoost(betaN=data$betaN, betaT=data$betaT, muN=data$muN) } if (is.element("betaTN", names)) { data$rhoN <- 2*abs(data$betaTN-1/2) data$rhoN[!data$isHet] <- NA_real_ data$c1N <- 1/2*(1-data$rhoN)*data$CT data$c2N <- data$CT - data$c1N } if (all(is.element(c("betaN", "betaT"), names))) { data$isSNP <- (!is.na(data$betaT) | !is.na(data$betaN)) data$type <- ifelse(data$isSNP, "SNP", "non-polymorphic locus") } } # Labels data$muNx <- c("AA", "AB", "BB")[2*data$muN + 1L] data$isHetx <- c("AA|BB", "AB")[data$isHet + 1L] } data }, protected=TRUE) # getLocusData() setMethodS3("resegment", "PairedPSCBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Resegmenting a ", class(fit)[1], " object") # Use the locus-level data of the PairedPSCBS object data <- getLocusData(fit) class(data) <- "data.frame" drop <- c("rho", "betaTN", "index") keep <- !is.element(colnames(data), drop) data <- data[,keep] verbose && str(verbose, data) verbose && cat(verbose, "Number of loci: ", nrow(data)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup arguments to be passed # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Overriding default arguments") segFcnName <- "segmentByPairedPSCBS" segFcn <- getMethodS3(segFcnName, "default") # (a) The default arguments formals <- formals(segFcn) formals <- formals[!sapply(formals, FUN=is.language)] formals <- formals[!sapply(formals, FUN=is.name)] drop <- c("chromosome", "x", "w", "CT", "thetaT", "thetaN", "betaT", "betaN", "muN", "rho", "preserveScale", "...") keep <- !is.element(names(formals), drop) formals <- formals[keep] # (b) The arguments used in previous fit params <- fit$params keep <- is.element(names(params), names(formals)) params <- params[keep] # Don't trust 'tbn'! TODO. /HB 20111117 params$tbn <- NULL # (c) The arguments in '...' userArgs <- list(..., verbose=verbose) # (d) Merge args <- formals args2 <- c(params, userArgs) for (kk in seq_along(args2)) { value <- args2[[kk]] if (!is.null(value)) { key <- names(args2)[kk] if (!is.null(key)) { args[[key]] <- value } else { args <- c(args, list(value)) } } } # for (key ...) verbose && str(verbose, args[names(args) != "verbose"]) verbose && enter(verbose, sprintf("Calling %s()", segFcnName)) args <- c(list(data), args) verbose && cat(verbose, "Arguments:") verbose && str(verbose, args[names(args) != "verbose"]) verbose && exit(verbose) fit <- do.call(segFcnName, args) verbose && exit(verbose) verbose && exit(verbose) fit }, protected=TRUE) # resegment() setMethodS3("adjustPloidyScale", "PairedPSCBS", function(fit, scale, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (a) Update locus-level data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) names <- c("CT") for (ff in names) { data[[ff]] <- scale * data[[ff]] } fit$data <- data ## fit <- setLocusData(fit, data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (b) Update segment-level data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- getSegments(fit) # Adjust segment levels names <- grep("^(tcn|c1|c2)(Mean|_.*%)$", names(segs), value=TRUE) for (ff in names) { segs[[ff]] <- scale * segs[[ff]] } # Clear segment calls names <- c("lohCall", "ntcnCall") for (ff in names) { segs[[ff]] <- NULL } fit$output <- segs ## fit <- setSegments(fit, sets) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (c) Update parameter estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - params <- fit$params fields <- c("copyNeutralStats", "deltaCN", "ntcnRange", "deltaLowC1") params[fields] <- NULL fit$params <- params fit }, protected=TRUE) # adjustPloidyScale() ############################################################################## # HISTORY # 2014-03-30 # o Update resegment() for PairedPSCBS to handle 'thetaT' and 'thetaN'. # 2013-10-25 # o BUG FIX: The 'rho' signals returned by getLocusData(..., fields="full") # for PairedPSCBS would have values also for homozygote SNPs. # 2013-03-08 # o Added getLocusData() for PairedPSCBS. # 2012-04-21 # o CLEANUP: Moved getSegmentSizes() from PairedPSCBS to PSCBS. # 2011-11-21 # o BUG FIX: resegment() was trying to call segmentByCBS() instead # of segmentByPairedPSCBS(). # 2011-11-17 # o Added resegment() for PairedPSCBS for easy resegmentation. # 2011-10-02 # o CLEANUP: Moved print() and as.data.frame() to PSCBS. # o Added Rdoc help. # o Now the constructor of PairedPSCBS calls that of PSCBS. # 2011-06-28 # o DOCUMENTATION: Added Rd help for as.data.frame() of PairedPSCBS. # 2011-04-08 # o Added formal constructor for the PairedPSCBS class. # o Created. ############################################################################## PSCBS/R/segmentByNonPairedPSCBS.R0000644000176200001440000002273014564051545016015 0ustar liggesusers###########################################################################/** # @RdocDefault segmentByNonPairedPSCBS # @alias segmentByNonPairedPSCBS.data.frame # @alias segmentByNonPairedPSCBS.PairedPSCBS # @alias segmentByNonPairedPSCBS # # @title "Segment total copy numbers and allele B fractions using the Non-paired PSCBS method" # # \description{ # @get "title" [1]. # This method does not requires matched normals. # This is a low-level segmentation method. # It is intended to be applied to one tumor sample at the time. # } # # @synopsis # # \arguments{ # \item{CT}{A @numeric @vector of J tumor total copy number (TCN) # ratios in [0,+@Inf) (due to noise, small negative values are # also allowed). The TCN ratios are typically scaled such that # copy-neutral diploid loci have a mean of two.} # \item{betaT}{A @numeric @vector of J tumor allele B fractions (BAFs) # in [0,1] (due to noise, values may be slightly outside as well) # or @NA for non-polymorphic loci.} # \item{...}{Additional arguments passed to @see "segmentByPairedPSCBS".} # \item{flavor}{A @character specifying what type of segmentation and # calling algorithm to be used.} # \item{tauA, tauB}{Lower and upper thresholds (\code{tauA < tauB} for # calling SNPs heterozygous based on the tumor allele B fractions # (\code{betaT}). If @NA, then they are estimates from data. # } # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the segmentation results as a @see "NonPairedPSCBS" object. # } # # \details{ # Internally @see "segmentByPairedPSCBS" is used for segmentation. # This segmentation method does \emph{not} support weights. # } # # \section{Reproducibility}{ # The "DNAcopy::segment" implementation of CBS uses approximation # through random sampling for some estimates. Because of this, # repeated calls using the same signals may result in slightly # different results, unless the random seed is set/fixed. # } # # \section{Whole-genome segmentation is preferred}{ # Although it is possible to segment each chromosome independently # using Paired PSCBS, we strongly recommend to segment whole-genome # (TCN,BAF) data at once. The reason for this is that downstream # CN-state calling methods, such as the AB and the LOH callers, # performs much better on whole-genome data. In fact, they may # fail to provide valid calls if done chromosome by chromosome. # } # # \section{Missing and non-finite values}{ # The total copy number signals as well as any optional positions # must not contain missing values, i.e. @NAs or @NaNs. # If there are any, an informative error is thrown. # Allele B fractions may contain missing values, because such are # interpreted as representing non-polymorphic loci. # # None of the input signals may have infinite values, i.e. -@Inf or +@Inf. # If so, an informative error is thrown. # } # # \section{Non-Paired PSCBS with known genotypes}{ # If allele B fractions for the matched normal (\code{betaN}) are # not available, but genotypes (\code{muN}) are, then it is possible # to run Paired PSCBS. See @see "segmentByPairedPSCBS" for details. # } # # @examples "../incl/segmentByNonPairedPSCBS.Rex" # # @author "HB" # # \references{ # [1] @include "../incl/OlshenA_etal_2011.Rd" \cr # [2] @include "../incl/BengtssonH_etal_2010.Rd" \cr # } # # \seealso{ # To segment paired tumor-normal total copy numbers and allele B fractions, # see @see "segmentByPairedPSCBS". # # To segment total copy numbers, or any other unimodal signals, # see @see "segmentByCBS". # } # # @keyword IO #*/########################################################################### setMethodS3("segmentByNonPairedPSCBS", "default", function(CT, betaT, ..., flavor=c("tcn", "tcn&dh", "tcn,dh", "sqrt(tcn),dh", "sqrt(tcn)&dh"), tauA=NA, tauB=1-tauA, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'CT': disallow <- c("Inf") CT <- Arguments$getDoubles(CT, disallow=disallow) nbrOfLoci <- length(CT) length2 <- rep(nbrOfLoci, times=2) # Argument 'betaT': betaT <- Arguments$getDoubles(betaT, length=length2, disallow="Inf") # Argument 'flavor': flavor <- match.arg(flavor) knownFlavors <- eval(formals(segmentByPairedPSCBS.default)$flavor, enclos = baseenv()) if (!is.element(flavor, knownFlavors)) { stop("Segmentation flavor is not among the supported ones (", paste(sprintf("\"%s\"", knownFlavors), collapse=", "), "): ", flavor) } # Argument 'tauA' & 'tauB': if (!is.na(tauA) && !is.na(tauB)) { tauA <- Arguments$getDouble(tauA) tauB <- Arguments$getDouble(tauB) if (tauB < tauA) { stop("Argument 'tauA' must be smaller than 'tauB': ", tauA, " > ", tauB) } tauA <- Arguments$getDouble(tauA, range=c(-0.5, +0.5)) tauB <- Arguments$getDouble(tauB, range=c(+0.5, +1.5)) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Segmenting non-paired tumor signals using Non-paired PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup input data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && cat(verbose, "Number of loci: ", nbrOfLoci) # SNPs are identifies as those loci that have non-missing 'betaT' isSnp <- !is.na(betaT) nbrOfSnps <- sum(isSnp) verbose && cat(verbose, "Number of SNPs: ", nbrOfSnps) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call tumor "genotypes" # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Calling \"genotypes\" from tumor allele B fractions") verbose && str(verbose, betaT) if (is.na(tauA) && is.na(tauB)) { mBAF <- abs(betaT - 1/2) fitT <- findPeaksAndValleys(mBAF) type <- NULL; rm(list="type") # To please 'R CMD check'. fitT <- subset(fitT, type == "peak") o <- order(fitT$density, decreasing=TRUE) fitT <- fitT[o,] fitT <- fitT[1,] z <- mBAF[mBAF >= fitT$x] - fitT$x q <- quantile(z, probs=0.95, na.rm=TRUE, names=FALSE) qU <- fitT$x+q verbose && cat(verbose, "Upper quantile: ", qU) qL <- fitT$x - q verbose && cat(verbose, "Symmetric lower quantile: ", qL) tauA <- 1/2-qL tauB <- 1/2+qL verbose && cat(verbose, "(tauA, tauB) estimates: (%g,%g)", tauA, tauB) # Sanity check on (tauA, tauB) estimates if (tauB < tauA) { stop("Failed to estimate (tauA, tauB). The estimate 'tauA' is greater than 'tauB', which it should not: ", tauA, " > ", tauB) } tauA <- Arguments$getDouble(tauA, range=c(-0.5, +0.5)) tauB <- Arguments$getDouble(tauB, range=c(+0.5, +1.5)) } verbose && cat(verbose, "Homozygous treshholds:") verbose && print(verbose, c(tauA, tauB)) isHomA <- isSnp & (betaT <= tauA) isHomB <- isSnp & (betaT >= tauB) isHom <- (isHomA | isHomB) isHet <- isSnp & !isHom # Tumor proxy for germline genotypes naValue <- NA_real_ muNx <- rep(naValue, times=length(betaT)) muNx[isHomA] <- 0 muNx[isHet] <- 1/2 muNx[isHomB] <- 1 # Not needed anymore isHomA <- isHomB <- isHom <- isHet <- NULL verbose && cat(verbose, "Inferred germline genotypes (via tumor):") verbose && str(verbose, muNx) verbose && print(verbose, table(muNx)) verbose && exit(verbose) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segment using Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Segment using Paired PSCBS") fit <- segmentByPairedPSCBS(CT=CT, betaT=betaT, muN=muNx, tbn=FALSE, flavor=flavor, ..., verbose=verbose) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Coerce fit object to Non-Paired PSCBS results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Coercing to Non-Paired PSCBS results") data <- fit$data class(data) <- gsub("PairedPSCNData", "NonPairedPSCNData", class(data), fixed=TRUE) # class(data) <- c("NonPairedPSCNData", class(data)) fit$data <- data # Not needed anymore data <- NULL segs <- fit$output class(segs) <- gsub("PairedPSCNSegments", "NonPairedPSCNSegments", class(segs), fixed=TRUE) # class(segs) <- c("NonPairedPSCNSegments", class(segs)) fit$output <- segs # Not needed anymore segs <- NULL params <- fit$params params$tauA <- tauA params$tauB <- tauB fit$params <- params # Not needed anymore params <- NULL # class(fit) <- gsub("PairedPSCBS", "NonPairedPSCBS", class(fit), fixed=TRUE) class(fit) <- c("NonPairedPSCBS", class(fit)) verbose && exit(verbose) verbose && print(verbose, head(as.data.frame(fit))) verbose && print(verbose, tail(as.data.frame(fit))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit }) # segmentByNonPairedPSCBS() setMethodS3("segmentByNonPairedPSCBS", "data.frame", function(CT, ...) { # To please R CMD check data <- CT segmentByNonPairedPSCBS(CT=data$CT, betaT=data$betaT, chromosome=data$chromosome, x=data$x, ...) }) setMethodS3("segmentByNonPairedPSCBS", "PairedPSCBS", function(...) { resegment(...) }) PSCBS/R/CBS.updateMeansTogether.R0000644000176200001440000000472514564051545016047 0ustar liggesuserssetMethodS3("updateMeansTogether", "CBS", function(fit, idxList, ..., avg=c("mean", "median"), verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(fit, splitters=TRUE) # Argument 'idxList': if (!is.list(idxList)) { idxList <- list(idxList) } idxList <- lapply(idxList, FUN=function(idxs) { idxs <- Arguments$getIndices(idxs, max=nbrOfSegments) sort(unique(idxs)) }) # Argument 'avg': avg <- match.arg(avg) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating mean level estimates of multiple segments") verbose && cat(verbose, "Segments:") verbose && str(verbose, idxList) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up averaging functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - avgFUN <- get(avg, mode="function") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit, splitters=TRUE) nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Total number of segments: ", nbrOfSegments) for (ss in seq_along(idxList)) { idxs <- idxList[[ss]] fitT <- extractSegments(fit, idxs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fitT)) dataT <- getLocusData(fitT) segsT <- getSegments(fitT) y <- dataT$y # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update the TCN segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Recalculate TCN means") # (c) Adjust for missing values keep <- which(!is.na(y)) # (d) Update mean gamma <- avgFUN(y[keep]) # Sanity check .stop_if_not(length(gamma) == 0 || !is.na(gamma)) mus <- c(mean=gamma) verbose && print(verbose, mus) verbose && exit(verbose) for (key in names(mus)) { segs[idxs,key] <- mus[key] } } # for (ss ...) # Return results res <- fit res$output <- segs res <- setMeanEstimators(res, y=avg) verbose && exit(verbose) res }, private=TRUE) # updateMeansTogether() PSCBS/R/PairedPSCBS.PLOT.R0000644000176200001440000006423514564202700014236 0ustar liggesusers###########################################################################/** # @set "class=PairedPSCBS" # @RdocMethod plotTracks1 # @aliasmethod plotTracks # @aliasmethod plotTracks2 # @aliasmethod plotTracksManyChromosomes # @alias plot # # @title "Plots parental specific copy numbers along the genome" # # \description{ # @get "title" for one or more chromosomes. # It is possible to specify what type of tracks to plot. # Each type of track is plotted in its own panel. # } # # @synopsis # # \arguments{ # \item{x}{A result object returned by @see "segmentByPairedPSCBS".} # \item{tracks}{A @character @vector specifying what types of tracks to plot.} # \item{scatter}{A @character @vector specifying which of the tracks should # have scatter plot.} # \item{calls}{A @character @vector of regular expression identifying # call labels to be highlighted in the panels.} # \item{pch}{The type of the scatter points, if any.} # \item{col}{The color of the scatter points, if any.} # \item{cex}{The size of the scatter points, if any.} # \item{changepoints}{If @TRUE, changepoints are drawn as vertical lines.} # \item{grid}{If @TRUE, horizontal lines are displayed.} # \item{quantiles}{A @numeric @vector in [0,1] specifying the quantiles # of the confidence bands to be drawn, if any.} # \item{xlim}{(Optional) The genomic range to plot.} # \item{Clim}{The range of copy numbers.} # \item{Blim}{The range of allele B fractions (BAFs) and # decrease of heterozygosity (DHs).} # \item{xScale}{The scale factor used for genomic positions.} # \item{...}{Not used.} # \item{add}{If @TRUE, the panels plotted are added to the existing plot, # otherwise a new plot is created.} # \item{subplots}{If @TRUE, then subplots are automatically setup.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns nothing. # } # # @author "HB" # # @keyword IO # @keyword internal #*/########################################################################### setMethodS3("plotTracks1", "PairedPSCBS", function(x, tracks=c("tcn", "dh", "tcn,c1,c2", "tcn,c1", "tcn,c2", "c1,c2", "betaN", "betaT", "betaTN")[1:3], scatter="*", calls=".*", pch=".", col=NULL, cex=1, changepoints=FALSE, grid=FALSE, quantiles=c(0.05,0.95), xlim=NULL, Clim=c(0,3*ploidy(x)), Blim=c(0,1), xScale=1e-6, ..., add=FALSE, subplots=!add && (length(tracks) > 1), verbose=FALSE) { # To please R CMD check fit <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'add': add <- Arguments$getLogical(add) # Argument 'Clim' & 'Blim': if (!add) { Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) Blim <- Arguments$getNumerics(Blim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) } # Argument 'fit': if (nbrOfChromosomes(fit) >= 1L) { return(plotTracksManyChromosomes(fit, tracks=tracks, scatter=scatter, calls=calls, pch=pch, quantiles=quantiles, Clim=Clim, Blim=Blim, xScale=xScale, ..., add=add, subplots=subplots, verbose=verbose)) } # Argument 'tracks': knownTracks <- c("tcn", "dh", "tcn,c1,c2", "tcn,c1", "tcn,c2", "c1,c2", "betaN", "betaT", "betaTN") tracks <- match.arg(tracks, choices=knownTracks, several.ok=TRUE) tracks <- unique(tracks) # Argument 'scatter': if (!is.null(scatter)) { scatter <- Arguments$getCharacter(scatter) if (scatter == "*") { scatter <- tracks } else { scatterT <- strsplit(scatter, split=",", fixed=TRUE) tracksT <- strsplit(tracks, split=",", fixed=TRUE) .stop_if_not(all(is.element(scatterT, tracksT))) # Not needed anymore scatterT <- tracksT <- NULL } } # Argument 'calls': if (!is.null(calls)) { calls <- sapply(calls, FUN=Arguments$getRegularExpression) } # Argument 'changepoints': changepoints <- Arguments$getLogical(changepoints) # Argument 'grid': grid <- Arguments$getLogical(grid) # Argument 'xlim': if (!is.null(xlim)) { xlim <- Arguments$getNumerics(xlim, length=c(2,2)) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Argument 'subplots': subplots <- Arguments$getLogical(subplots) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Plotting PSCN tracks") # Extract the input data data <- getLocusData(fit) if (is.null(data)) { stop("Cannot plot segmentation results. No input data available.") } chromosomes <- getChromosomes(fit) chromosome <- chromosomes[1] x <- data$x CT <- data$CT rho <- data$rho betaT <- data$betaT betaN <- data$betaN betaTN <- data$betaTN muN <- data$muN rho <- data$rho hasDH <- !is.null(rho) if (hasDH) { isHet <- !is.na(rho) isSnp <- isHet } else { isSnp <- (!is.na(betaTN) & !is.na(muN)) isHet <- isSnp & (muN == 1/2) } nbrOfLoci <- length(x) # BACKWARD COMPATIBILITY: # If 'rho' is not available, recalculate it from tumor BAFs. # NOTE: This should throw an error in the future. /HB 2013-10-25 if (!hasDH) { rho <- rep(NA_real_, times=nbrOfLoci) rho[isHet] <- 2*abs(betaTN[isHet]-1/2) warning(sprintf("Locus-level DH signals ('rho') were not available in the %s object and therefore recalculated from the TumorBoost-normalized tumor BAFs ('betaTN').", class(fit)[1L])) } # Extract the segmentation segs <- as.data.frame(fit) # Identify available calls if (!is.null(calls)) { verbose && enter(verbose, "Identifying calls") pattern <- "Call$" callColumns <- grep(pattern, colnames(segs), value=TRUE) if (length(callColumns) > 0) { keep <- sapply(calls, FUN=function(pattern) { (regexpr(pattern, callColumns) != -1) }) if (is.matrix(keep)) { keep <- rowAnys(keep, useNames=FALSE) } callColumns <- callColumns[keep] callLabels <- gsub(pattern, "", callColumns) callLabels <- toupper(callLabels) } verbose && cat(verbose, "Call columns:") verbose && print(verbose, callColumns) verbose && exit(verbose) } else { callColumns <- NULL } if (chromosome != 0) { chrTag <- sprintf("Chr%02d", chromosome) } else { chrTag <- "" } if (xScale != 1) { x <- xScale * x if (!is.null(xlim)) { xlim <- xScale * xlim } } if (subplots) { subplots(length(tracks), ncol=1) par(mar=c(1,4,1,2)+1) } # Color loci by heterozygous vs homozygous if (hasDH) { colMu <- c("gray", "black")[!is.na(rho) + 1] } else { colMu <- c("gray", "black")[(muN == 1/2) + 1] } for (tt in seq_along(tracks)) { track <- tracks[tt] verbose && enter(verbose, sprintf("Track #%d ('%s') of %d", tt, track, length(tracks))) if (!is.null(scatter)) { pchT <- pch colT <- col } else { pchT <- NA colT <- NA } if (track == "tcn") { colT <- ifelse(is.null(colT), "black", colT) if (add) { points(x, CT, pch=pchT, col=colT, cex=cex) } else { plot(x, CT, pch=pchT, col=colT, cex=cex, xlim=xlim, ylim=Clim, ylab="TCN") stext(side=3, pos=1, chrTag) if (grid) { abline(h=seq(from=0, to=Clim[2], by=2), lty=3, col="gray") abline(h=0, lty=1, col="black") } drawConfidenceBands(fit, what="tcn", quantiles=quantiles, col="purple", xScale=xScale) drawLevels(fit, what="tcn", col="purple", xScale=xScale) } } if (is.element(track, c("tcn,c1,c2", "tcn,c1", "tcn,c2", "c1,c2"))) { colT <- ifelse(is.null(colT), "black", colT) subtracks <- strsplit(track, split=",", fixed=TRUE)[[1]] ylab <- paste(toupper(subtracks), collapse=", ") if (add) { points(x, CT, pch=pchT, cex=cex, col=colT) } else { plot(x, CT, pch=pchT, cex=cex, col=colT, xlim=xlim, ylim=Clim, ylab=ylab) stext(side=3, pos=1, chrTag) if (grid) { abline(h=seq(from=0, to=Clim[2], by=2), lty=3, col="gray") abline(h=0, lty=1, col="black") } if (is.element("tcn", subtracks)) { drawConfidenceBands(fit, what="tcn", quantiles=quantiles, col="purple", xScale=xScale) } if (is.element("c2", subtracks)) { drawConfidenceBands(fit, what="c2", quantiles=quantiles, col="red", xScale=xScale) } if (is.element("c1", subtracks)) { drawConfidenceBands(fit, what="c1", quantiles=quantiles, col="blue", xScale=xScale) } if (is.element("tcn", subtracks)) { drawLevels(fit, what="tcn", col="purple", xScale=xScale) } if (is.element("c2", subtracks)) { drawLevels(fit, what="c2", col="red", xScale=xScale) # In case C2 overlaps with TCN if (is.element("tcn", subtracks)) { drawLevels(fit, what="tcn", col="purple", lty="22", xScale=xScale) } } if (is.element("c1", subtracks)) { drawLevels(fit, what="c1", col="blue", xScale=xScale) # In case C1 overlaps with C1 if (is.element("c2", subtracks)) { drawLevels(fit, what="c2", col="red", lty="22", xScale=xScale) if (is.element("tcn", subtracks)) { drawLevels(fit, what="tcn", col="purple", lty="22", xScale=xScale) } } } } } if (track == "betaN") { colT <- ifelse(is.null(colT), colMu, colT) if (add) { points(x, betaN, pch=pchT, cex=cex, col="black") } else { plot(x, betaN, pch=pchT, cex=cex, col=colT, xlim=xlim, ylim=Blim, ylab=expression(BAF[N])) stext(side=3, pos=1, chrTag) } } if (track == "betaT") { colT <- ifelse(is.null(colT), colMu, colT) if (add) { points(x, betaT, pch=pchT, cex=cex, col="black") } else { plot(x, betaT, pch=pchT, cex=cex, col=colT, xlim=xlim, ylim=Blim, ylab=expression(BAF[T])) stext(side=3, pos=1, chrTag) } } if (track == "betaTN") { colT <- ifelse(is.null(colT), colMu, colT) if (add) { points(x, betaTN, pch=pchT, cex=cex, col="black") } else { plot(x, betaTN, pch=pchT, cex=cex, col=colT, xlim=xlim, ylim=Blim, ylab=expression(BAF[T]^"*")) stext(side=3, pos=1, chrTag) } } if (track == "dh") { colT <- ifelse(is.null(colT), colMu[isHet], colT) if (add) { points(x, rho, pch=pchT, cex=cex, col="black") } else { plot(x, rho, pch=pchT, cex=cex, col=colT, xlim=xlim, ylim=Blim, ylab="DH") stext(side=3, pos=1, chrTag) drawConfidenceBands(fit, what="dh", quantiles=quantiles, col="orange", xScale=xScale) drawLevels(fit, what="dh", col="orange", xScale=xScale) } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Draw change points? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (changepoints) { drawChangePoints(fit, col="#666666", xScale=xScale) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each panel of tracks, annotate with calls? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (length(callColumns) > 0) { for (cc in seq_along(callColumns)) { callColumn <- callColumns[cc] callLabel <- callLabels[cc] verbose && enter(verbose, sprintf("Call #%d ('%s') of %d", cc, callLabel, length(callColumns))) verbose && cat(verbose, "Column: ", callColumn) segsT <- segs[,c("dhStart", "dhEnd", callColumn)] isCalled <- which(segsT[[callColumn]]) segsT <- segsT[isCalled,1:2,drop=FALSE] verbose && printf(verbose, "Number of segments called %s: %d\n", callLabel, nrow(segsT)) segsT <- xScale * segsT verbose && str(verbose, segsT) side <- 2*((cc+1) %% 2) + 1 # For each segment called... for (ss in seq_len(nrow(segsT))) { x0 <- segsT[ss,1,drop=TRUE] x1 <- segsT[ss,2,drop=TRUE] abline(v=c(x0,x1), lty=3, col="gray") xMid <- (x0+x1)/2 mtext(side=side, at=xMid, line=-1, cex=0.7, col="#666666", callLabel) } # for (ss in ...) verbose && exit(verbose) } # for (cc in ...) # Add call parameter estimates, e.g. deltaAB for (cc in seq_along(callColumns)) { callColumn <- callColumns[cc] callLabel <- callLabels[cc] h <- NULL if (callLabel == "AB") { if (track == "dh") { h <- fit$params$deltaAB label <- expression(Delta[AB]) colT <- "orange" } } else if (callLabel == "LOH") { if (regexpr("c1", track) != -1L) { h <- fit$params$deltaLowC1 label <- expression(Delta[LOH]) colT <- "blue" } } else if (callLabel == "NTCN") { if (track == "tcn") { h <- fit$params$ntcnRange label <- c(expression(Delta[-NTCN]), expression(Delta[+NTCN])) colT <- "purple" } } if (!is.null(h)) { abline(h=h, lty=4, lwd=2, col=colT) for (ss in 1:2) { side <- c(2,4)[ss] adj <- c(1.2,-0.2)[ss] mtext(side=side, at=h, label, adj=adj, las=2, xpd=TRUE) } } } # for (cc in ...) } # if (length(callColumns) > 0) verbose && exit(verbose) } # for (tt ...) verbose && exit(verbose) invisible() }, private=TRUE) # plotTracks1() setMethodS3("plotTracks", "PairedPSCBS", function(fit, ...) { plotTracksManyChromosomes(fit, ...) }) setMethodS3("plot", "PairedPSCBS", function(x, ...) { plotTracks(x, ...) }, private=TRUE) setMethodS3("drawLevels", "PairedPSCBS", function(fit, what=c("tcn", "betaTN", "dh", "c1", "c2"), lend=1L, xScale=1e-6, ...) { # WORKAROUND: If Hmisc is loaded after R.utils, it provides a buggy # capitalize() that overrides the one we want to use. Until PSCBS # gets a namespace, we do the following workaround. /HB 2011-07-14 capitalize <- R.utils::capitalize # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'what': what <- match.arg(what) # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # Get segmentation results segs <- as.data.frame(fitT) if (what == "betaTN") { whatT <- "dh" } else { whatT <- what } # Extract subset of segments fields <- c("start", "end") fields <- sprintf("%s%s", ifelse(what == "tcn", what, "dh"), capitalize(fields)) fields <- c(fields, sprintf("%sMean", whatT)) segsT <- segs[,fields, drop=FALSE] segsT <- unique(segsT) if (what == "betaTN") { dh <- segsT[,"dhMean"] bafU <- (1 + dh)/2 bafL <- (1 - dh)/2 segsT[,3] <- bafU segsT[,4] <- bafL } # Reuse drawLevels() for the DNAcopy class for (cc in seq(from=3, to=ncol(segsT))) { segsTT <- segsT[,c(1:2,cc)] colnames(segsTT) <- c("loc.start", "loc.end", "seg.mean") dummy <- list(output=segsTT) class(dummy) <- "DNAcopy" drawLevels(dummy, lend=lend, xScale=xScale, ...) } # for (cc ...) }, private=TRUE) setMethodS3("drawConfidenceBands", "PairedPSCBS", function(fit, what=c("tcn", "dh", "c1", "c2"), quantiles=c(0.05,0.95), col=col, alpha=0.4, xScale=1e-6, ...) { # WORKAROUND: If Hmisc is loaded after R.utils, it provides a buggy # capitalize() that overrides the one we want to use. Until PSCBS # gets a namespace, we do the following workaround. /HB 2011-07-14 capitalize <- R.utils::capitalize # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'what': what <- match.arg(what) # Argument 'quantiles': if (!is.null(quantiles)) { quantiles <- Arguments$getNumerics(quantiles, range=c(0,1), length=c(2,2)) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Nothing todo? if (is.null(quantiles)) { return() } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # Get segmentation results segs <- as.data.frame(fitT) # Extract subset of segments fields <- c("start", "end") fields <- sprintf("%s%s", ifelse(what == "tcn", what, "dh"), capitalize(fields)) tags <- sprintf("%g%%", 100*quantiles) qFields <- sprintf("%s_%s", what, tags) # Nothing todo? if (!all(is.element(qFields, colnames(segs)))) { return() } fields <- c(fields, qFields) segsT <- segs[,fields, drop=FALSE] segsT <- unique(segsT) # Rescale x-axis segsT[,1:2] <- xScale * segsT[,1:2] colQ <- col2rgb(col, alpha=TRUE) colQ["alpha",] <- alpha*colQ["alpha",] colQ <- rgb(red=colQ["red",], green=colQ["green",], blue=colQ["blue",], alpha=colQ["alpha",], maxColorValue=255) for (kk in seq_len(nrow(segsT))) { rect(xleft=segsT[kk,1], xright=segsT[kk,2], ybottom=segsT[kk,3], ytop=segsT[kk,4], col=colQ, border=FALSE) } }, private=TRUE) setMethodS3("plotC1C2", "PairedPSCBS", function(fit, ..., xlab=expression(C[1]), ylab=expression(C[2]), Clim=c(0,2*ploidy(fit))) { # Argument 'Clim': Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) plot(NA, xlim=Clim, ylim=Clim, xlab=xlab, ylab=ylab) abline(a=0, b=1, lty=3) pointsC1C2(fit, ...) }, private=TRUE) setMethodS3("pointsC1C2", "PairedPSCBS", function(fit, cex=NULL, col="#00000033", ...) { data <- extractC1C2(fit) X <- data[,1:2,drop=FALSE] n <- data[,4,drop=TRUE] n <- sqrt(n) w <- n / sum(n, na.rm=TRUE) if (is.null(cex)) { cex <- w cex <- cex / mean(cex, na.rm=TRUE) cex <- cex + 1/2 } points(X, cex=cex, col=col, ...) }, private=TRUE) setMethodS3("linesC1C2", "PairedPSCBS", function(fit, ...) { drawChangePointsC1C2(fit, ...) }, private=TRUE) setMethodS3("drawChangePointsC1C2", "PairedPSCBS", function(fit, col="#00000033", labels=FALSE, lcol="#333333", cex=0.7, adj=c(+1.5,+0.5), ...) { xy <- extractMinorMajorCNs(fit, splitters=TRUE, addGaps=TRUE) xy <- xy[,1:2,drop=FALSE] res <- lines(xy, col=col, ...) if (labels) { n <- nrow(xy) dxy <- (xy[-1,] - xy[-n,]) / 2 xyMids <- xy[-n,] + dxy labels <- rownames(xy) labels <- sprintf("%s-%s", labels[-n], labels[-1]) text(xyMids, labels, cex=cex, col=lcol, adj=adj, ...) } invisible(res) }, private=TRUE) setMethodS3("plotDeltaC1C2", "PairedPSCBS", function(fit, ..., xlab=expression(Delta*C[1]), ylab=expression(Delta*C[2]), Clim=c(-1,1)*ploidy(fit)) { # Argument 'Clim': Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) plot(NA, xlim=Clim, ylim=Clim, xlab=xlab, ylab=ylab) abline(h=0, lty=3) abline(v=0, lty=3) pointsDeltaC1C2(fit, ...) }, private=TRUE) setMethodS3("pointsDeltaC1C2", "PairedPSCBS", function(fit, ...) { data <- extractDeltaC1C2(fit) X <- data[,1:2,drop=FALSE] points(X, ...) }, private=TRUE) setMethodS3("linesDeltaC1C2", "PairedPSCBS", function(fit, ...) { xy <- extractDeltaC1C2(fit) xy <- xy[,1:2,drop=FALSE] lines(xy, ...) }, private=TRUE) setMethodS3("arrowsC1C2", "PairedPSCBS", function(fit, length=0.05, ...) { xy <- extractMinorMajorCNs(fit, splitters=TRUE, addGaps=TRUE) xy <- xy[,1:2,drop=FALSE] x <- xy[,1,drop=TRUE] y <- xy[,2,drop=TRUE] s <- seq_len(length(x)-1) arrows(x0=x[s],y0=y[s], x1=x[s+1],y1=y[s+1], code=2, length=length, ...) }, private=TRUE) setMethodS3("arrowsDeltaC1C2", "PairedPSCBS", function(fit, length=0.05, ...) { xy <- extractDeltaC1C2(fit) xy <- xy[,1:2,drop=FALSE] x <- xy[,1,drop=TRUE] y <- xy[,2,drop=TRUE] s <- seq_len(length(x)-1) arrows(x0=x[s],y0=y[s], x1=x[s+1],y1=y[s+1], code=2, length=length, ...) }, private=TRUE) setMethodS3("tileChromosomes", "PairedPSCBS", function(fit, chrStarts=NULL, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'chrStarts': if (!is.null(chrStarts)) { chrStarts <- Arguments$getDoubles(chrStarts) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # Nothing to do, i.e. already tiled? if (isTRUE(attr(fit, "tiledChromosomes"))) { return(fit) } verbose && enter(verbose, "Tile chromosomes") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit) knownSegments <- fit$params$knownSegments # Identify all chromosome chromosomes <- getChromosomes(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Additional chromosome annotations # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.null(chrStarts)) { xRange <- matrix(0, nrow=length(chromosomes), ncol=2) for (kk in seq_along(chromosomes)) { chromosome <- chromosomes[kk] idxs <- which(data$chromosome == chromosome) x <- data$x[idxs] r <- range(x, na.rm=TRUE) r <- r / 1e6 r[1] <- floor(r[1]) r[2] <- ceiling(r[2]) r <- 1e6 * r xRange[kk,] <- r } # for (kk ...) chrLength <- xRange[,2] chrStarts <- c(0, cumsum(chrLength)[-length(chrLength)]) chrEnds <- chrStarts + chrLength # Not needed anymore x <- idxs <- NULL } # if (is.null(chrStarts)) verbose && cat(verbose, "Chromosome starts:") chromosomeStats <- cbind(start=chrStarts, end=chrEnds, length=chrEnds-chrStarts) verbose && print(chromosomeStats) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Offset... # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segFields <- grep("(Start|End)$", colnames(segs), value=TRUE) # Sanity check .stop_if_not(length(segFields) > 0) for (kk in seq_along(chromosomes)) { chromosome <- chromosomes[kk] chrTag <- sprintf("Chr%02d", chromosome) verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", kk, chrTag, length(chromosomes))) # Get offset for this chromosome offset <- chrStarts[kk] verbose && cat(verbose, "Offset: ", offset) # Offset data idxs <- which(data$chromosome == chromosome) if (length(idxs) > 0L) { data$x[idxs] <- offset + data$x[idxs] } # Offset segmentation idxs <- which(segs$chromosome == chromosome) if (length(idxs) > 0L) { segs[idxs,segFields] <- offset + segs[idxs,segFields] } # Offset known segments idxs <- which(knownSegments$chromosome == chromosome) if (length(idxs) > 0L) { knownSegments[idxs,c("start", "end")] <- offset + knownSegments[idxs,c("start", "end")] } verbose && exit(verbose) } # for (kk ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit$data <- data fit$output <- segs fit$chromosomeStats <- chromosomeStats fit$params$knownSegments <- knownSegments # fitT$params$chrOffsets <- chrOffsets # Flag object attr(fit, "tiledChromosomes") <- TRUE verbose && exit(verbose) fit }, private=TRUE) # tileChromosomes() setMethodS3("drawChangePoints", "PSCBS", function(fit, labels=FALSE, col="#666666", cex=0.5, xScale=1e-6, side=3, line=-1, xpd=TRUE, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) verbose && str(verbose, fitT) segs <- getSegments(fitT, splitters=FALSE) xStarts <- segs[,"tcnStart"] xEnds <- segs[,"tcnEnd"] xs <- sort(unique(c(xStarts, xEnds))) abline(v=xScale*xs, lty=1, col=col) if (labels) { xMids <- xScale * (xEnds + xStarts) / 2 labels <- rownames(segs) mtext(side=side, at=xMids, labels, line=line, cex=cex, col=col, xpd=xpd, ...) } }, protected=TRUE) setMethodS3("getChromosomeRanges", "PairedPSCBS", function(fit, ...) { # To please R CMD check, cf. subset() chromosome <- NULL; rm(list="chromosome") segs <- getSegments(fit, splitters=FALSE) chromosomes <- sort(unique(segs$chromosome)) # Allocate naValue <- NA_real_ res <- matrix(naValue, nrow=length(chromosomes), ncol=3) rownames(res) <- chromosomes colnames(res) <- c("start", "end", "length") # Get start and end of each chromosome. for (ii in seq_len(nrow(res))) { chr <- chromosomes[ii] segsII <- subset(segs, chromosome == chr) res[ii,"start"] <- min(segsII$tcnStart, na.rm=TRUE) res[ii,"end"] <- max(segsII$tcnEnd, na.rm=TRUE) } # for (ii ...) res[,"length"] <- res[,"end"] - res[,"start"] + 1L # Sanity check .stop_if_not(nrow(res) == length(chromosomes)) res <- as.data.frame(res) res <- cbind(chromosome=chromosomes, res) res }, protected=TRUE) # getChromosomeRanges() setMethodS3("getChromosomeOffsets", "PairedPSCBS", function(fit, resolution=1e6, ...) { # Argument 'resolution': if (!is.null(resolution)) { resolution <- Arguments$getDouble(resolution, range=c(1,Inf)) } data <- getChromosomeRanges(fit, ...) splits <- data[,"start"] + data[,"length"] if (!is.null(resolution)) { splits <- ceiling(splits / resolution) splits <- resolution * splits } offsets <- c(0L, cumsum(splits)) names(offsets) <- c(rownames(data), NA) offsets }, protected=TRUE) # getChromosomeOffsets() PSCBS/R/AbstractCBS.clearCalls.R0000644000176200001440000000133214564051545015617 0ustar liggesusers# Removes all segment calls and corresponding parameter estimates. setMethodS3("clearCalls", "AbstractCBS", function(fit, ...) { segs <- fit$output params <- fit$params # Drop all calls excl <- grep("Call$", colnames(segs)) if (length(excl) > 0L) { segs <- segs[,-excl] } # Drop all call parameters (AD HOC!) for (ff in c("deltaROH", "deltaAB", "deltaLOH")) { params[[ff]] <- NULL } fit$output <- segs fit$params <- params invisible(fit) }, protected=TRUE) ############################################################################## # HISTORY # 2013-10-24 # o Added clearCalls() for AbstractCBS. # o Created. ############################################################################## PSCBS/R/exampleData.R0000644000176200001440000000207114564051545013706 0ustar liggesusers###########################################################################/** # @RdocDefault exampleData # # @title "Gets an example data set" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{name}{A @character string specifying the name of the data set.} # \item{...}{Not used.} # } # # \value{ # Returns @data.frame. # } # # @author "HB" # # @keyword IO # @keyword data # @keyword internal #*/########################################################################### setMethodS3("exampleData", "default", function(name=c("paired.chr01"), ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'name': name <- match.arg(name) path <- system.file("data-ex", package="PSCBS", mustWork=TRUE) if (name == "paired.chr01") { filename <- "PairedPSCBS,exData,chr01.Rbin" } pathname <- Arguments$getReadablePathname(filename, path=path) data <- loadObject(pathname) data }, protected=TRUE) PSCBS/R/PairedPSCBS.estimateKappa.R0000644000176200001440000001663414564051545016261 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateKappa # # @title "Estimate global background in segmented copy numbers" # # \description{ # @get "title". # The global background, here called \eqn{\kappa}, # may have multiple origins where normal contamination is one, # but not necessarily the only one. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # estimator to use.} # \item{...}{Additional arguments passed to the estimator.} # } # # \value{ # Returns the background estimate as a @numeric scalar. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "estimateKappaByC1Density". # } # #*/########################################################################### setMethodS3("estimateKappa", "PairedPSCBS", function(this, flavor=c("density(C1)"), ...) { # Argument 'flavor': flavor <- match.arg(flavor) if (flavor == "density(C1)") { estimateKappaByC1Density(this, ...) } else { stop("Cannot estimate background. Unsupported flavor: ", flavor) } }) ###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateKappaByC1Density # # @title "Estimate global background in segmented copy numbers" # # \description{ # @get "title" based on the location of peaks in a weighted # density estimator of the minor copy number mean levels. # # The global background, here called \eqn{\kappa}, # may have multiple origins where normal contamination is one, # but not necessarily the only one. # # \emph{Assumptions:} This estimator assumes that there are segments # with C1=0 and C1=1, i.e. some deletions and, typically, some normal # segements. # } # # @synopsis # # \arguments{ # \item{typeOfWeights}{A @character string specifying how weights # are calculated.} # \item{adjust}{A @numeric scale factor specifying the size of # the bandwidth parameter used by the density estimator.} # \item{from}{A @numeric scalar specifying the lower bound for the # support of the estimated density.} # \item{minDensity}{A non-negative @numeric threshold specifying # the minimum density a peak should have in order to consider # it a peak.} # \item{...}{Not used.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the background estimate as a @numeric scalar. # } # # \section{Algorithm}{ # \itemize{ # \item Retrieve segment-level minor copy numbers and corresponding weights: # \enumerate{ # \item Grabs the segment-level C1 estimates. # \item Calculate segment weights. # The default (\code{typeOfWeights="dhNbrOfLoci"}) is to use # weights proportional to the number of heterozygous SNPs. # An alternative (\code{typeOfWeights="sqrt(dhNbrOfLoci)"}) is # to use the square root of those counts. # } # # \item Identify subset of regions with C1=0: # \enumerate{ # \item Estimates the weighted empirical density function # (truncated at zero below). Tuning parameter 'adjust'. # \item Find the first two peaks # (with a density greater than tuning parameter 'minDensity'). # \item Assumes that the two peaks corresponds to C1=0 and C1=1. # \item Defines threshold Delta0.5 as the center location between # these two peaks. # } # # \item Estimate the global background signal: # \enumerate{ # \item For all segments with C1 < Delta0.5, calculate the weighted # median of their C1:s. # \item Let kappa be the above weighted median. # This is the estimated background. # } # } # } # # @author "HB" # # \seealso{ # Instead of calling this method explicitly, it is recommended # to use the @seemethod "estimateKappa" method. # } # # @keyword internal #*/########################################################################### setMethodS3("estimateKappaByC1Density", "PairedPSCBS", function(this, typeOfWeights=c("dhNbrOfLoci", "sqrt(dhNbrOfLoci)"), adjust=1, from=0, minDensity=0.2, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'typeOfWeights': typeOfWeights <- match.arg(typeOfWeights) # Argument 'adjust': adjust <- Arguments$getDouble(adjust, range=c(0,Inf)) # Argument 'minDensity': minDensity <- Arguments$getDouble(minDensity, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimate global background (including normal contamination and more)") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the region-level estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- this$output c1 <- segs$c1Mean .stop_if_not(!is.null(c1)) n <- segs$dhNbrOfLoci # Drop missing values keep <- (!is.na(c1) & !is.na(n)) c1 <- c1[keep] n <- n[keep] verbose && cat(verbose, "Number of segments: ", length(c1)) # Calculate region weights if (typeOfWeights == "dhNbrOfLoci") { w <- n } else if (typeOfWeights == "sqrt(dhNbrOfLoci)") { w <- sqrt(n) } # Standardize weights to sum to one weights <- w / sum(w) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify subset of regions with C1=0 and C1=1 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Estimating threshold Delta0.5 from the empirical density of C1:s") verbose && cat(verbose, "adjust: ", adjust) verbose && cat(verbose, "minDensity: ", minDensity) ploidy <- ploidy(this) verbose && cat(verbose, "ploidy: ", ploidy) if (ploidy != 2) { minDensity <- (2/ploidy)*minDensity verbose && cat(verbose, "minDensity (adjusted for ploidy): ", minDensity) } d <- density(c1, weights=weights, adjust=adjust, from=from, na.rm=FALSE) fit <- findPeaksAndValleys(d) type <- NULL; rm(list="type") # To please R CMD check fit <- subset(fit, type == "peak") if (nrow(fit) < 2L) { stop(sprintf("Less than two modes were found in the empirical density of C1: %d", nrow(fit))) } nModes <- nrow(fit) fit <- subset(fit, density >= minDensity) if (nrow(fit) < 2L) { stop(sprintf("Less than two modes were found in the empirical density of C1 after removing %d modes that are too weak (density < %g): %d", nModes - nrow(fit), minDensity, nrow(fit))) } nModes <- nrow(fit) verbose && cat(verbose, "All peaks:") verbose && print(verbose, fit) # Keep the first two peaks fit <- fit[1:2,,drop=FALSE] verbose && cat(verbose, "C1=0 and C1=1 peaks:") verbose && print(verbose, fit) peaks <- fit$x Delta0.5 <- mean(peaks) verbose && cat(verbose, "Estimate of Delta0.5: ", Delta0.5) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Estimate kappa # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - keep <- which(c1 < Delta0.5) verbose && cat(verbose, "Number of segments with C1 < Delta0.5: ", length(keep)) kappa <- weightedMedian(c1[keep], w=weights[keep]) # Adjust for ploidy kappa <- (2/ploidy)*kappa verbose && cat(verbose, "Estimate of kappa: ", kappa) verbose && exit(verbose) kappa }, protected=TRUE) # estimateKappaByC1Density() PSCBS/R/CBS.SMOOTH.R0000644000176200001440000000305714564051545013105 0ustar liggesusers###########################################################################/** # @set class=CBS # @RdocMethod getSmoothLocusData # # @title "Gets smoothed locus-level data" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{fit}{An @see "CBS" object.} # \item{by}{A @numeric scalar specifying the bin size.} # \item{...}{Not used.} # } # # \value{ # Returns a @data.frame where the # first three columns are 'chromosome', 'x' (position), # and 'count' (number of loci average over for the given bin), # and the remaining ones are the smoothed locus-level data. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("getSmoothLocusData", "CBS", function(fit, by, ...) { # Argument 'by': by <- Arguments$getNumeric(by, range=c(0,Inf)) chromosomes <- getChromosomes(fit) data <- getLocusData(fit) chromosome <- NULL; rm(list="chromosome") # To please R CMD check dataS <- NULL for (kk in seq_along(chromosomes)) { chr <- chromosomes[kk] dataT <- subset(data, chromosome == chr) x <- dataT$x y <- dataT$y rx <- range(x, na.rm=TRUE) bx <- seq(from=rx[1], to=rx[2], by=by) xS <- bx[-1] - by/2 yS <- binMeans(y=y, x=x, bx=bx) count <- attr(yS, "count") yS[count == 0L] <- NA_real_ attr(yS, "count") <- NULL dataTS <- data.frame(chromosome=chr, x=xS, count=count, y=yS) dataS <- rbind(dataS, dataTS) } # for (kk ...) dataS }, protected=TRUE) # getSmoothLocusData() PSCBS/R/PairedPSCBS.callGNL.R0000644000176200001440000002355414564051545014744 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod callGNL # @aliasmethod callGainNeutralLoss # @alias callGNLByTCNofAB # @aliasmethod callGNLByTCNofAB # @alias callGNLByTCNofABv1 # @aliasmethod callGNLByTCNofABv1 # # @title "Calls segments that are gained, copy neutral, or lost" # # \description{ # @get "title", where copy neutral means having a total copy number # that corresponds to the ploidy of the genome. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # call to use.} # \item{...}{Additional arguments passed to the caller.} # \item{minSize}{An optional @integer specifying the minimum number # of data points in order to call a segments. If fewer data points, # then the call is set to @NA regardless.} # \item{force}{If @FALSE, and copy-neutral calls already exits, # then nothing is done, otherwise the calls are done.} # } # # \value{ # Returns a @see "PairedPSCBS" object with added calls. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # \code{callGNLByTCNofAB()}. # } # #*/########################################################################### setMethodS3("callGNL", "PairedPSCBS", function(fit, flavor=c("TCN|AB"), ..., minSize=1, force=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'minSize': minSize <- Arguments$getDouble(minSize, range=c(1,Inf)) # Already done? segs <- as.data.frame(fit) if (!force && all(is.element(c("gainCall", "ntcnCall", "lossCall"), names(segs)))) { # Segments are already called return(invisible(fit)) } if (flavor == "TCN|AB") { fit <- callGNLByTCNofAB(fit, ..., force=force) } else { stop("Cannot call allelic balance. Unsupported flavor: ", flavor) } # Don't call segments with too few data points? if (minSize > 1) { segs <- as.data.frame(fit) ns <- segs$dhNbrOfLoci calls <- segs$ntcnCall calls[ns < minSize] <- NA segs$ntcnCall <- calls fit$output <- segs # Not needed anymore segs <- calls <- NULL } return(invisible(fit)) }) # callGNL() setMethodS3("callGainNeutralLoss", "PairedPSCBS", function(...) { callGNL(...) }) setMethodS3("callGNLByTCNofAB", "PairedPSCBS", function(fit, ..., minSize=1L, force=FALSE, verbose=FALSE) { # Argument 'minSize': minSize <- Arguments$getDouble(minSize, range=c(1,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling gain, neutral, and loss based TCNs of AB segments") # Already done? segs <- as.data.frame(fit) called <- all(is.element(c("gainCall", "ntcnCall", "lossCall"), names(segs))) if (!force && called) { return(invisible(fit)) } verbose && enter(verbose, "Calling neutral TCNs") fit <- callCopyNeutralByTCNofAB(fit, ..., verbose=verbose) verbose && exit(verbose) # The segment data segs <- as.data.frame(fit) tcnMean <- segs$tcnMean nbrOfSegs <- nrow(segs) # The call thresholds and the NTCN calls ntcnCall <- call <- segs$ntcnCall verbose && printf(verbose, "Number of NTCN calls: %d (%.2f%%) of %d\n", sum(call, na.rm=TRUE), 100*sum(call, na.rm=TRUE)/nbrOfSegs, nbrOfSegs) params <- fit$params deltaCN <- params$deltaCN .stop_if_not(!is.null(deltaCN)) ntcnRange <- params$ntcnRange .stop_if_not(!is.null(ntcnRange)) # Confidence interval of the TCN|AB segments range <- ntcnRange + c(+1,-1)*deltaCN # Mean of the TCN|AB segments mu <- mean(range, na.rm=TRUE) verbose && printf(verbose, "Mean TCN of AB segments: %g\n", mu) verbose && enter(verbose, "Calling loss") call <- !ntcnCall & (tcnMean < mu) segs$lossCall <- call verbose && printf(verbose, "Number of loss calls: %d (%.2f%%) of %d\n", sum(call, na.rm=TRUE), 100*sum(call, na.rm=TRUE)/nbrOfSegs, nbrOfSegs) verbose && exit(verbose) verbose && enter(verbose, "Calling gain") call <- !ntcnCall & (tcnMean > mu) segs$gainCall <- call verbose && printf(verbose, "Number of loss calls: %d (%.2f%%) of %d\n", sum(call, na.rm=TRUE), 100*sum(call, na.rm=TRUE)/nbrOfSegs, nbrOfSegs) verbose && exit(verbose) # Recording fit$output <- segs verbose && exit(verbose) fit }) # callGNLByTCNofAB() setMethodS3("callGNLByTCNofABv1", "PairedPSCBS", function(fit, deltaLoss=-0.5, deltaGain=+0.5, alpha=0.05, ..., force=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'alpha': disallow <- c("NA", "NaN", "Inf") alpha <- Arguments$getDouble(alpha, range=c(0,0.5), disallow=disallow) # Argument 'deltaLoss' & 'deltaGain': disallow <- c("NA", "NaN", "Inf") deltaLoss <- Arguments$getDouble(deltaLoss, range=c(-Inf,0), disallow=disallow) deltaGain <- Arguments$getDouble(deltaGain, range=c(0,+Inf), disallow=disallow) # Argument 'force': force <- Arguments$getLogical(force) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "callGNLByTCNofAB") verbose && cat(verbose, "Alpha: ", alpha) verbose && cat(verbose, "Delta loss: ", deltaLoss) verbose && cat(verbose, "Delta gain: ", deltaGain) segs <- getSegments(fit, splitters=TRUE, simplify=FALSE) # Already done? if (!force && all(is.element(c("gainCall", "ntcnCall", "lossCall"), names(segs)))) { # Segments are already called verbose && cat(verbose, "Already called. Skipping.") verbose && exit(verbose) return(invisible(fit)) } # Check that bootstrap estimates exists keys <- sprintf("tcn_%g%%", 100*c(alpha/2, 1-alpha/2)) missing <- keys[!is.element(keys, colnames(segs))] if (length(missing) > 0) { stop("No such statistics: ", hpaste(missing)) } verbose && enter(verbose, "Calling segments") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Confidence interval of copy-neutral AB segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Estimating TCN confidence interval of copy-neutral AB segments") fit <- calcStatsForCopyNeutralABs(fit, ..., verbose=less(verbose, 5)) stats <- fit$params$copyNeutralStats verbose && cat(verbose, "Bootstrap statistics for copy-neutral AB segments:") verbose && print(verbose, stats) # Extract TCN stats cols <- grep("^(tcn_|tcnMean)", colnames(stats)) tcnStats <- stats[,cols,drop=FALSE] tcnStats <- unlist(tcnStats, use.names=TRUE) verbose && print(verbose, "TCN statistics:") verbose && print(verbose, tcnStats) # Extract confidence interval of interest keys <- sprintf("tcn_%g%%", 100*c(alpha/2, 1-alpha/2)) missing <- keys[!is.element(keys, names(tcnStats))] if (length(missing) > 0) { stop("No such statistics: ", hpaste(missing)) } mean <- tcnStats["tcnMean"] ci <- tcnStats[keys] verbose && printf(verbose, "%g%%-confidence interval of TCN mean for the copy-neutral state: [%g,%g] (mean=%g)\n", 100*(1-alpha), ci[1], ci[2], mean) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get call regions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - naValue <- NA_real_ callRegions <- matrix(c( Inf, 1, 1, 1, 1, Inf ), nrow=3, ncol=2, byrow=TRUE) rownames(callRegions) <- c("loss", "ntcn", "gain") colnames(callRegions) <- c("lower", "upper") callRegions["loss",] <- ci[1]+callRegions["loss",]*deltaLoss callRegions["ntcn",] <- ci +callRegions["ntcn",]*c(deltaLoss, deltaGain) callRegions["gain",] <- ci[2]+callRegions["gain",]*deltaGain verbose && cat(verbose, "Call (\"acceptance\") regions:") verbose && print(verbose, callRegions) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get statistics for all segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegs <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegs) nbrOfABs <- sum(segs$abCall, na.rm=TRUE) verbose && cat(verbose, "Number of AB segments: ", nbrOfABs) verbose && cat(verbose, "Number of non-AB segments: ", nbrOfSegs-nbrOfABs) # Get TCN confidence intervals for all segments keys <- sprintf("tcn_%g%%", 100*c(alpha/2, 1-alpha/2)) ci <- segs[,keys] # Call states for (rr in seq_len(nrow(callRegions))) { state <- rownames(callRegions)[rr] verbose && enter(verbose, "Identify all '", state, "' segments") range <- callRegions[rr,] verbose && printf(verbose, "Call (\"acceptance\") region: [%g,%g]\n", range[1], range[2]) # If a confidence interval is completely within the # calling region, call it isCalled <- (range[1] <= ci[,1] & ci[,2] < range[2]) nbrOfCalled <- sum(isCalled, na.rm=TRUE) verbose && cat(verbose, "Number of segments called '", state, "': ", nbrOfCalled) ## verbose && cat(verbose, "Number of non-AB segments called '", state, "': ", (nbrOfSegs-nbrOfABs)-nbrOfCalled) key <- sprintf("%sCall", state) segs[[key]] <- isCalled verbose && exit(verbose) } # for (rr ...) fitC <- fit fitC$output <- segs verbose && exit(verbose) fitC }, protected=TRUE) # callGNLByTCNofABv1() ############################################################################## # HISTORY # 2013-09-20 [HB] # o BUG FIX: callGNL() for PairedPSCBS used non-defined 'verbose' object. # 2012-03-22 [HB] # o Renamed 'cnCall' to 'ntcnCall' for callGNLByTCNofAB(). # 2012-02-26 [HB] # o Added internal callGNLByTCNofAB(). # o Added callGNL(). ############################################################################## PSCBS/R/findLargeGaps.R0000644000176200001440000000647014564051545014176 0ustar liggesusers###########################################################################/** # @RdocDefault findLargeGaps # @alias findLargeGaps.data.frame # # @title "Identifies gaps of a genome where there exist no observations" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{chromosome}{(Optional) An @integer @vector of length J of # chromosome indices.} # \item{x}{A @numeric @vector of J of genomic locations.} # \item{minLength}{A positive @numeric scalar specifying the minimum # length of a gap.} # \item{resolution}{A non-negative @numeric specifying the minimum # length unit, which by default equals one nucleotide/base pair.} # \item{...}{Not used.} # } # # \value{ # Returns @data.frame zero or more rows and with columns # \code{chromosome} (if given), \code{start}, \code{stop}, # and \code{length}. # } # # @author "HB" # # \seealso{ # Use @see "gapsToSegments" to turn the set of identified gaps into # the complementary set of segments such that they can be passed # to @see "segmentByCBS", @see "segmentByPairedPSCBS" and # @see "segmentByNonPairedPSCBS" via argument \code{knownSegments}. # } # # @keyword IO #*/########################################################################### setMethodS3("findLargeGaps", "default", function(chromosome=NULL, x, minLength, resolution=1L, ...) { # Argument 'x': x <- Arguments$getNumerics(x) nbrOfLoci <- length(x) # Argument 'chromosome': if (!is.null(chromosome)) { disallow <- c("Inf") chromosome <- Arguments$getIntegers(chromosome, range=c(0,Inf), disallow=disallow, length=c(nbrOfLoci, nbrOfLoci)) } # Argument 'minLength': minLength <- Arguments$getNumeric(minLength, range=c(0,Inf)) # Argument 'resolution': resolution <- Arguments$getNumeric(resolution, range=c(0,Inf)) if (resolution >= minLength) { stop(sprintf("Cannot identify large gaps. Argument 'resolution' (=%g) is not strictly smaller than 'minLength' (=%g).", resolution, minLength)) } if (!is.null(chromosome)) { allChromosomes <- sort(unique(chromosome)) nbrOfChromosomes <- length(allChromosomes) xEmpty <- vector(mode(x), length=0L) gaps <- data.frame(chromosome=integer(0L), start=xEmpty, end=xEmpty) for (cc in seq_along(allChromosomes)) { chr <- allChromosomes[cc] idxs <- which(chromosome == chr) chromosomeCC <- chromosome[idxs] xCC <- x[idxs] gapsCC <- findLargeGaps(chromosome=NULL, x=xCC, minLength=minLength, ...) if (nrow(gapsCC) > 0) { gapsCC <- cbind(chromosome=chr, gapsCC) gaps <- rbind(gaps, gapsCC) } } # for (cc ...) } else { x <- x[is.finite(x)] x <- sort(x) dx <- diff(x) isGap <- (dx >= minLength) idxsL <- which(isGap) ##str(list(x=x, dx=dx, isGap=isGap, idxsL=idxsL)) xL <- x[idxsL] xR <- x[idxsL+1L] ##str(list(x=x, dx=dx, isGap=isGap, idxsL=idxsL, xL=xL, xR=xR)) gaps <- data.frame(start=xL+resolution, end=xR-resolution) gaps$length <- gaps$end - gaps$start } ## Sanity checks .stop_if_not(is.data.frame(gaps)) .stop_if_not(all(gaps$start <= gaps$end)) .stop_if_not(all(gaps$length >= 0)) gaps }) # findLargeGaps() setMethodS3("findLargeGaps", "data.frame", function(chromosome, ...) { data <- chromosome findLargeGaps(chromosome=data$chromosome, x=data$x, ...) }) # findLargeGaps() PSCBS/R/AbstractCBS.PRUNE.R0000644000176200001440000004101714564051545014447 0ustar liggesuserssetMethodS3("seqOfSegmentsByDP", "AbstractCBS", function(fit, by, shift=+100, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'by': by <- Arguments$getCharacters(by) data <- getLocusData(fit) fields <- colnames(data) missing <- fields[!is.element(by, fields)] if (length(missing) > 0) { stop("Argument 'by' specifies one or more non-existing locus data fields: ", paste(missing, collapse=", ")) } # Argument 'shift': shift <- Arguments$getNumeric(shift) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Identifying optimal sets of segments via dynamic programming") # Assert that known segments was used knownSegments <- fit$params$knownSegments if (nrow(knownSegments) == 0L) { chromosome <- getChromosomes(fit) knownSegments <- data.frame(chromosome=chromosome, start=-Inf, end=+Inf) } chrOffsets <- getChromosomeOffsets(fit) # Sanity check .stop_if_not(all(is.finite(chrOffsets))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Shift every other non-empty region # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Shifting TCN levels for every second segment") segPrefix <- getSegmentTrackPrefixes(fit)[1L] segKeys <- toCamelCase(paste(segPrefix, c("start", "end"))) segRowsKey <- toCamelCase(paste(segPrefix, "seg rows")) verbose && enter(verbose, "Split up into non-empty independent regions") chromosomes <- getChromosomes(fit) fitList <- list() for (jj in seq_along(chromosomes)) { chr <- chromosomes[jj] verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", jj, chr, length(chromosomes))) # Subset segmentation results on this chromosome fitJJ <- extractChromosome(fit, chr) verbose && cat(verbose, "Number of loci on chromosome: ", nbrOfLoci(fitJJ)) # Nothing to do and nothing to add? if (nbrOfLoci(fitJJ) == 0L) { verbose && exit(verbose) next } # Find known segments on this chromosome knownSegmentsJJ <- subset(knownSegments, chromosome == chr) verbose && cat(verbose, "Known segments on chromosome:") verbose && print(verbose, knownSegmentsJJ) # Nothing to do? if (nrow(knownSegmentsJJ) == 0L) { fitList <- append(fitList, list(fitJJ)) verbose && exit(verbose) next } # Get the segments on this chromosome segsJJ <- getSegments(fitJJ) # Extract the individual known segments on this chromosome fitListJJ <- list() for (kk in seq_len(nrow(knownSegmentsJJ))) { verbose && enter(verbose, sprintf("Known segment #%d of %d", kk, nrow(knownSegmentsJJ))) seg <- knownSegmentsJJ[kk,] verbose && print(verbose, seg) start <- seg$start end <- seg$end idxStart <- min(which(segsJJ[[segKeys[1]]] >= start)) idxEnd <- max(which(segsJJ[[segKeys[2]]] <= end)) idxs <- idxStart:idxEnd # Extract the particular known segment fitKK <- extractSegments(fitJJ, idxs) # Only add if it has loci if (nbrOfLoci(fitKK) > 0L) { fitListJJ <- append(fitListJJ, list(fitKK)) } fitKK <- NULL # Not needed anymore verbose && exit(verbose) } # for (kk ...) # Append fitList <- append(fitList, fitListJJ) fitListJJ <- NULL # Not needed anymore verbose && exit(verbose) } # for (jj ...) nbrOfRegions <- length(fitList) verbose && cat(verbose, "Number of independent non-empty regions: ", nbrOfRegions) verbose && exit(verbose) verbose && enter(verbose, "Shift every other region") for (jj in seq(from=1L, to=nbrOfRegions, by=2L)) { fitJJ <- fitList[[jj]] fitJJ <- shiftTCN(fitJJ, shift=shift) fitList[[jj]] <- fitJJ } # for (jj ...) verbose && exit(verbose) verbose && enter(verbose, "Merge") ## former Reduce() w/ append(a, b, addSplit = FALSE) fitT <- do.call(c, args = c(fitList, addSplit = FALSE)) # Sanity check ## .stop_if_not(nbrOfSegments(fitT) == nbrOfSegments(fit)) # Not true anymore verbose && exit(verbose) fitList <- NULL # Not needed anymore segsT <- getSegments(fitT) verbose && print(verbose, tail(segsT)) verbose && exit(verbose) fit <- fitT # Not needed anymore fitT <- knownSegments <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract signals for DP # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Extracting signals for dynamic programming") fit <- tileChromosomes(fit) # Locus-level signals data <- getLocusData(fit) Y <- as.matrix(data[,by,drop=FALSE]) verbose && print(verbose, summary(Y)) # "DP" change-point indices (excluding the two outer/boundary ones) segRows <- fit[[segRowsKey]] segIdxs <- seq_len(nrow(segRows)-1L) cpIdxs <- segRows$endRow[segIdxs] verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Dynamic-programming segmention pruning # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Dynamic programming") verbose && cat(verbose, "Number of \"DP\" change points: ", length(cpIdxs)) verbose && str(verbose, cpIdxs) res <- seqOfSegmentsByDP(Y, candidatechangepoints=cpIdxs, ...) verbose && str(verbose, res) # Sanity checks jumpList <- res$jump lastJump <- jumpList[[length(jumpList)]] .stop_if_not(identical(cpIdxs, as.integer(lastJump))) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Adjustments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Excluding cases where known segments no longer correct") verbose && cat(verbose, "Number of independent non-empty regions: ", nbrOfRegions) # Drop the K first nbrOfCPs <- nbrOfRegions - 1L if (nbrOfCPs > 0L) { K <- nbrOfCPs - 1L # Don't count the flat segmentation jumpList <- jumpList[-(1:K)] } verbose && str(verbose, jumpList) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the possible sets of segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose <- less(verbose, 20) verbose && enter(verbose, "Converting to physical segments") segs <- getSegments(fit, splitters=TRUE, addGaps=FALSE) segs <- segs[,c("chromosome", segKeys)] jumpIdxList <- lapply(jumpList, FUN=function(idxs) { match(idxs, table=cpIdxs) }) # Sanity check .stop_if_not(identical(seq_along(cpIdxs), jumpIdxList[[length(jumpIdxList)]])) chrs <- segs$chromosome starts <- segs[[segKeys[1]]] ends <- segs[[segKeys[2]]] nsegs <- nrow(segs) segList <- vector("list", length=length(jumpIdxList)) for (kk in seq_along(segList)) { verbose && enter(verbose, sprintf("Sequence #%d of %d", kk, length(segList))) idxs <- jumpIdxList[[kk]] verbose && cat(verbose, "Change point indices:") verbose && str(verbose, idxs) chrsKK <- chrs[idxs] chr <- chrsKK[1] # .stop_if_not(all(chrsKK == chr)) chrsKK <- c(chrsKK, chrsKK[length(chrsKK)]) startsKK <- starts[c(1L, idxs+1L)] endsKK <- ends[c(idxs, nsegs)] verbose && cat(verbose, "Chromosomes:") verbose && str(verbose, chrsKK) verbose && cat(verbose, "Starts:") verbose && str(verbose, startsKK) verbose && cat(verbose, "Ends:") verbose && str(verbose, endsKK) offsetsKK <- chrOffsets[chrsKK] startsKK <- startsKK - offsetsKK endsKK <- endsKK - offsetsKK segsKK <- data.frame(chromosome=chrsKK, start=startsKK, end=endsKK) verbose && print(verbose, tail(segsKK)) segList[[kk]] <- segsKK verbose && exit(verbose) } # for (kk ...) verbose && exit(verbose) verbose <- more(verbose, 20) # Sanity check lastSegs <- segList[[length(segList)]] # .stop_if_not(identical(lastSegs, segs)) verbose && str(verbose, segList) nbrOfCPsSeq <- sapply(jumpList, FUN=length) verbose && cat(verbose, "Sequence of number of \"DP\" change points:") verbose && print(verbose, nbrOfCPsSeq) nbrOfSegsSeq <- sapply(segList, FUN=nrow) verbose && cat(verbose, "Sequence of number of segments:") verbose && print(verbose, nbrOfSegsSeq) nbrOfChangePointsSeq <- nbrOfSegsSeq - nbrOfRegions verbose && cat(verbose, "Sequence of number of \"discovered\" change points:") verbose && print(verbose, nbrOfChangePointsSeq) .stop_if_not(all(nbrOfSegsSeq == nbrOfCPsSeq + 1L)) .stop_if_not(nbrOfSegsSeq[1L] == nbrOfRegions) segList <- lapply(segList, FUN=function(seg) { attr(seg, "nbrOfChangePoints") <- nrow(seg) - nbrOfRegions seg }) K <- (nbrOfRegions-1L) modelFit <- list( nbrOfSegments=nbrOfSegsSeq, nbrOfChangePoints=nbrOfSegsSeq - nbrOfRegions, nbrOfRegions=nbrOfRegions, idxBest=res$kbest - K + 1L, rse=res$rse[-(1:K)], V=res$V[-(1:K),-(1:K),drop=FALSE], seqOfSegmentsByDP=res ) attr(segList, "modelFit") <- modelFit verbose && exit(verbose) segList }, protected=TRUE) # seqOfSegmentsByDP() setMethodS3("seqOfSegmentsByDP", "matrix", function( ### Segmentation of a multi-dimensional signal with dynamic programming. Y, ### A n*p signal to be segmented candidatechangepoints = c(1:(n-1)), ### A vector of candidate positions for change-points (default=[1:n-1]) kmax = n-1, ### Maximum number of change-points to test (default : n-1) threshold = 0.5, ### Stopping criteria. Typically chosen to be in the interval ### (0 0.5]. The smaller the threshold, the higher the tendency to keep more ### changepoints. The criteria is based on the method found in 'Picard et al ### (2005)', "A statistical approach for array CGH data analysis" (BMC ### Bioinformatics). Default=0.5 ... ){ n <- dim(Y)[1] p <- dim(Y)[2] kmaxmin <- floor(n/4) if (kmax == 0 || kmax > length(candidatechangepoints)) { kmax <- min(length(candidatechangepoints), kmaxmin) } if (kmax > kmaxmin) { sprintf('warning : not enough points to optimize the number of the change-points up to %s\n', kmax) kmax <- kmaxmin sprintf('Set the maximum number of change-points to %s\n', kmax) } # Compute boundaries of the smallest intervals considered b <- sort(union(0, union(n, candidatechangepoints))) k <- length(b) - 1 # k is the number of such intervals # Compute the k*k matrix J such that J[i,j] for i<=j is the RSE when intervales i to j are merged J <- matrix(numeric(k*k), ncol=k) # How should NAs be handled?!? Yz <- Y Yz[is.na(Yz)] <- 0 s <- rbind(rep(0, times=p), colCumsums(Yz, useNames=FALSE)) v <- c(0, cumsum(rowSums(Y^2, na.rm=TRUE))) for (i in 1:k) { for (j in i:k) { Istart <- b[i] + 1 Iend <- b[j+1] J[i,j] <- v[Iend+1] - v[Istart] - sum((s[Iend+1,]-s[Istart,])^2, na.rm=TRUE)/(Iend-Istart+1) } # for (j ...) } # for (i ...) # Dynamic programming V <- matrix(numeric((kmax+1)*k), ncol=k) # V[i,j] is the best RSE for segmenting intervals 1 to j with at most i-1 change points jump <- matrix(numeric(kmax*k), ncol=k) # With no change points, V[i,j] is juste the precomputed RSE for intervals 1 to j V[1,] <- J[1,] # Then we apply the recursive formula for (ki in 1:kmax) { for (j in (ki+1):k) { val <- min(V[ki,ki:(j-1)] + t(J[(ki+1):j, j])) ind <- which.min(V[ki,ki:(j-1)] + t(J[(ki+1):j, j])) V[ki+1,j] <- val jump[ki,j] <- ind + ki-1 } # for (j ...) } # for (ki ...) # Optimal segmentation res.jump <- list() for (ki in 1:kmax) { res.jump[[ki]] <- numeric(ki) res.jump[[ki]][ki] <- jump[ki,k] if (ki != 1) { for (i in seq(from=(ki-1), to=1, by=-1)) { res.jump[[ki]][i] <- jump[i, res.jump[[ki]][i+1]] } } } # for (ki ...) # Convert back the index of the interval to the last position before the jump rightlimit <- b[2:length(b)] for (ki in 1:kmax) { res.jump[[ki]] <- rightlimit[res.jump[[ki]]] } # for (ki ...) # RSE as a function of number of change-points res.rse <- V[,k] # Optimal number of change points options(warn=-1) J <- log(res.rse) Km <- length(J) Jtild <- (J[Km]-J)/(J[Km]-J[1])*(Km-1)+1 # Normalize res.kbest <- max(which(diff(diff(Jtild)) > threshold)) + 1 #if((res.kbest) == -Inf) { res.kbest <- 1 } return(list(jump=res.jump, rse=res.rse, kbest=res.kbest, V=V)) ### \item{res.jump{i}}{a i*1 vector of change-point positions for the i-th lambda value (i depends on lambda). i varies between 1 and kmax} ### \item{res.rse}{a (kmax+1)-dimensional vector of residual squared error} ### \item{res.kbest}{the number of selected change-points} }) # seqOfSegmentsByDP() ###########################################################################/** # @set class=AbstractCBS # @RdocMethod pruneByDP # # @title "Prunes the CN profile using dynamical programming" # # \description{ # @get "title" by specifying the target number of segments or alternative # how of many change points to drop. # } # # @synopsis # # \arguments{ # \item{nbrOfSegments}{An @integer specifying the number of segments after # pruning. If negative, the it specifies the number of change points # to drop.} # \item{...}{Optional arguments passed to @seemethod "seqOfSegmentsByDP".} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a pruned object of the same class. # } # # \examples{\dontrun{ # # Drop two segments # fitP <- pruneByDP(fit, nbrOfSegments=-2) # }} # # @author "HB, PN" # # \references{ # [1] ... \cr # } # # @keyword internal #*/########################################################################### setMethodS3("pruneByDP", "AbstractCBS", function(fit, nbrOfSegments, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Some pre-extraction # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - knownSegments <- fit$params$knownSegments if (nrow(knownSegments) == 0L) { chromosome <- getChromosomes(fit) knownSegments <- data.frame(chromosome=chromosome, start=-Inf, end=+Inf) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'nbrOfSegments': nbrOfSegments <- Arguments$getInteger(nbrOfSegments) # Specifying number of change points *to drop*? if (nbrOfSegments < 0L) { nbrOfCPsToDrop <- -nbrOfSegments nbrOfSegments <- nbrOfSegments(fit, splitters=FALSE) - nbrOfCPsToDrop } if (nbrOfSegments < nrow(knownSegments)) { stop("Argument 'nbrOfSegments' is less than number of \"known\" segments: ", nbrOfSegments, " < ", nrow(knownSegments)) } if (nbrOfSegments > nbrOfSegments(fit, splitters=FALSE)) { stop("Argument 'nbrOfSegments' is greater than the number of \"found\" segments: ", nbrOfSegments, " > ", nbrOfSegments(fit, splitters=FALSE)) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Prune segments by dynamical programming") # Nothing to do? if (nbrOfSegments == nbrOfSegments(fit, splitters=FALSE)) { verbose && cat(verbose, "No need for pruning, because the number of \"target\" segments is the same as the number of \"found\" segments: ", nbrOfSegments, " == ", nbrOfSegments(fit, splitters=FALSE)) return(fit) verbose && exit(verbose) } verbose && cat(verbose, "Target number of segments: ", nbrOfSegments) verbose && enter(verbose, "Dynamic programming") segList <- seqOfSegmentsByDP(fit, ...) # Select the one with expected number of segments nbrOfCPs <- sapply(segList, FUN=nrow) verbose && printf(verbose, "Range of number of CPs among solutions: [%d,%d]\n", min(nbrOfCPs), max(nbrOfCPs)) keep <- which(nbrOfCPs == nbrOfSegments) .stop_if_not(length(keep) == 1L) knownSegments <- segList[[keep]] verbose && printf(verbose, "Solution with %d segments:\n", nbrOfSegments) verbose && print(verbose, knownSegments) verbose && exit(verbose) verbose && enter(verbose, "Rebuilding segmentation results") fitDP <- resegment(fit, knownSegments=knownSegments, undoTCN=+Inf, undoDH=+Inf, verbose=less(verbose, 10)) verbose && print(verbose, fitDP) verbose && exit(verbose) verbose && exit(verbose) fitDP }, protected=TRUE) # pruneByDP() PSCBS/R/findNeutralCopyNumberState.R0000644000176200001440000001431114564051545016741 0ustar liggesusers###########################################################################/** # @RdocDefault findNeutralCopyNumberState # # @title "Call segments to be copy neutral based on allelic imbalance calls and total copy number estimates" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{C}{A @numeric @vector of region-level total copy number estimates.} # \item{isAI}{A @logical @vector of "allelic imbalance" calls.} # \item{weights}{An optional @numeric @vector of non-negative weights.} # \item{...}{Further arguments to be passed to the density estimation # function.} # \item{minDensity}{A @numeric value, below which density peaks are # discarded.} # \item{flavor}{A @character string specifying how to identify the # mode of the AB segments.} # \item{verbose}{If @TRUE, extra information is output.} # } # # \value{ # A @logical @vector of "neutral copy number state" calls. # } # # @author "PN, HB" # # @keyword internal #*/########################################################################### setMethodS3("findNeutralCopyNumberState", "default", function(C, isAI, weights=NULL, ..., minDensity=1e-10, flavor=c("firstPeak", "maxPeak"), verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'C': C <- Arguments$getNumerics(C) nbrOfLoci <- length(C) # Argument 'isAI': length2 <- rep(nbrOfLoci, times=2) isAI <- Arguments$getLogicals(isAI, length=length2, disallow=NULL) # Argument 'weights': if (!is.null(weights)) { weights <- Arguments$getNumerics(weights, range=c(0, Inf), length=length2) } # Argument 'minDensity': minDensity <- Arguments$getDouble(minDensity) # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Identifying segments that are copy neutral states") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify segments in allelic balance isAB <- !isAI # Identify segments that cannot be called isNA <- (is.na(isAB) | is.na(C)) # Only segments in allelic balance can be considered to be neutral isNeutral <- isAB # Extracting segments in allelic balance idxs <- which(isAB) n <- length(idxs) verbose && cat(verbose, "Number of segments in allelic balance: ", n) # Special cases? if (n == 0) { # No segments are in allelic balance verbose && exit(verbose) return(isNeutral) } else if (n == 1) { # Only one segment is in allelic balance. The best we can do # is to call that segment neutral. verbose && exit(verbose) return(isNeutral) } else if (n < 5) { # What to do when the number of segments is really low? /HB 2010-09-09 warning("The calling of regions in a copy-neutral state is uncertain, because there are less than five (5) regions in allelic balance: ", n) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Look only segments in allelic balance # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset and standardize weights if (!is.null(weights)) { weights <- weights[idxs] weights <- weights / sum(weights) } y <- C[idxs] idxs <- NULL # Not needed anymore if (verbose) { cat(verbose, "Data points:") df <- data.frame(C=y, weights=weights) print(verbose, head(df)) str(verbose, df) df <- NULL # Not needed anymore } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Estimate the empirical density # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- findPeaksAndValleys(y, weights=weights, ...) verbose && cat(verbose, "Fit:") verbose && cat(verbose, "Fit filtered by 'minDensity':") ok <- (fit[,"density"] > minDensity) verbose && print(verbose, fit[ok,]) # Look for peaks with enough density isPeak <- (fit[,"type"] == "peak") & ok idxs <- which(isPeak) # Sanity check .stop_if_not(length(idxs) >= 1) # Extract the first peak if (flavor == "firstPeak") { idx <- idxs[1] } else if (flavor == "maxPeak") { idx <- idxs[which.max(fit[idxs,"density"])] } neutralC <- fit[idx,"x"] verbose && cat(verbose, "Neutral copy number:") verbose && cat(verbose, "Mode at: ", neutralC) verbose && cat(verbose, "Mode ampliture: ", fit[idx,"density"]) # If there is more than one peak, we should only call segments that # are not part of that other peak. if (idx+1 <= nrow(fit)) { nextValleyC <- fit[idx+1, "x"] } else { nextValleyC <- Inf } verbose && cat(verbose, "Upper range at: ", nextValleyC) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call copy-neutral regions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - isNeutral <- isNeutral & (C < nextValleyC) # Segments with missing values cannot be called isNeutral[isNA] <- NA verbose && cat(verbose, "Neutral region calls:") verbose && summary(verbose, isNeutral) verbose && exit(verbose) isNeutral }) # findNeutralCopyNumberState() ############################################################################## # HISTORY # 2013-09-26 [HB] # o CLEANUP: Now findNeutralCopyNumberState() no longer attached # 'aroma.light', but only loads its namespace. # 2013-03-19 [HB] # o Added argument 'flavor' to findNeutralCopyNumberState() specifying how # to identify the main mode of the AB segments. # 2012-02-24 [HB] # o Moved findNeutralCopyNumberState() from aroma.light. # 2012-02-23 [HB] # o Renamed argument 'densityThreshold' to 'minDensity'. # 2011-07-10 [HB] # o Made findNeutralCopyNumberState() a default method. # o Made the Rd help "internal". # 2010-09-09 [HB] # o Now segments with missing values are not called. # o Added support for the case when there is no peak/no segments in AB. # o Added support for the case when there is only one weak. # o Added sanity checks. # 2010-09-08 [PN] # o Created. ############################################################################## PSCBS/R/PairedPSCBS.PLOT,many.R0000644000176200001440000004442114564051545015203 0ustar liggesusers# \item{chromosomes}{An optional @numeric @vector specifying which # chromosomes to plot.} # # \item{seed}{An (optional) @integer specifying the random seed to be # set before subsampling. The random seed is # set to its original state when exiting. If @NULL, it is not set.} # # \item{verbose}{See @see "R.utils::Verbose".} # setMethodS3("plotTracksManyChromosomes", "PairedPSCBS", function(fit, chromosomes=getChromosomes(fit), tracks=NULL, scatter="*", calls=if (callLoci || length(chromosomes) == 1L) ".*" else NULL, callLoci=FALSE, callThresholds=TRUE, boundaries=TRUE, knownSegments=FALSE, quantiles=c(0.05,0.95), seed=0xBEEF, pch=".", Clim=c(0,3*ploidy(fit)), Blim=c(0,1), xScale=1e-6, xlabTicks=if (length(chromosomes) == 1L) "[pos]" else "[chr]", ..., subset=if (length(chromosomes) > 1L) 0.1 else NULL, add=FALSE, subplots=!add && (length(tracks) > 1L), oma=c(0,0,2,0), mar=c(2,5,1,3)+0.1, onBegin=NULL, onEnd=NULL, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - attachGH <- function(gh, envir=parent.frame()) { if (!is.list(gh)) return() if (is.null(gh$track)) return() if (!is.null(value <- gh$track)) assign("track", value, envir=envir) if (!is.null(value <- gh$subtracks)) assign("trackT", value, envir=envir) if (!is.null(value <- gh$scatter$col)) assign("colS", value, envir=envir) if (!is.null(value <- gh$scatter$pch)) assign("pchT", value, envir=envir) if (!is.null(value <- gh$level$col)) assign("colL", value, envir=envir) if (!is.null(value <- gh$cis$col)) assign("colC", value, envir=envir) } # attachGH() # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Graphical styles # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - opts <- list( scatter = list(pch=".", col=c("#aaaaaa")), callScatter = list(col=c("#aaaaaa", LOSS="blue", GAIN="red", LOH="purple")), smoothScatter = list(pch=".", col=c("#666666")), level = list(lty=1L, col=c("black", tcn="purple", c1="blue", c2="red", dh="orange")), callLevel = list(lty=1L, col=c("#666666")), knownSegment = list(lty=1L, col=c("#aaaaaa")) ) getOptionValue <- function(option, what, track, ...) { values <- opts[[option]][[what]] value <- values[track] if (is.na(value)) value <- values[1L] unname(value) } # getOptionValue() getScatterColor <- function(track, ...) { getOptionValue("scatter", "col", track, ...) } # getScatterColor() getLevelColor <- function(track, ...) { getOptionValue("level", "col", track, ...) } # getLevelColor() getCallScatterColor <- function(track, ...) { getOptionValue("callScatter", "col", track, ...) } # getCallScatterColor() getCallLevelColor <- function(track, ...) { getOptionValue("callLevel", "col", track, ...) } # getCallLevelColor() getCallLevelLty <- function(track, ...) { getOptionValue("callLevel", "lty", track, ...) } # getCallLevelColor() getCIColor <- function(track, ...) { getLevelColor(track, ...) } # getLevelColor() getKnownSegmentColor <- function(track, ...) { getOptionValue("knownSegment", "col", track, ...) } # getKnownSegmentColor() getKnownSegmentLty <- function(track, ...) { getOptionValue("knownSegment", "lty", track, ...) } # getKnownSegmentColor() drawXLabelTicks <- function() { if (identical(xlabTicks, "[chr]")) { mtext(text=chrTags, side=rep(c(1,3), length.out=length(chrTags)), at=mids, line=0.1, cex=0.7) } else if (identical(xlabTicks, "[pos]")) { axis(side=1L) } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': # Argument 'chromosomes': if (!is.null(chromosomes)) { disallow <- c("NaN", "Inf") chromosomes <- Arguments$getIntegers(chromosomes, range=c(0,Inf), disallow=disallow) .stop_if_not(all(is.element(chromosomes, getChromosomes(fit)))) } # Argument 'tracks': knownTracks <- c("tcn", "dh", "tcn,c1,c2", "c1,c2", "c1", "c2", "betaN", "betaT", "betaTN") defaultTracks <- knownTracks[1:3] if (is.null(tracks)) { tracks <- defaultTracks } else { tracks <- match.arg(tracks, choices=knownTracks, several.ok=TRUE) tracks <- unique(tracks) } # Argument 'scatter': if (!is.null(scatter)) { scatter <- Arguments$getCharacter(scatter) if (scatter == "*") { scatter <- tracks } else { scatterT <- strsplit(scatter, split=",", fixed=TRUE) tracksT <- strsplit(tracks, split=",", fixed=TRUE) .stop_if_not(all(is.element(scatterT, tracksT))) # Not needed anymore scatterT <- tracksT <- NULL } } # Argument 'calls': if (!is.null(calls)) { calls <- sapply(calls, FUN=Arguments$getRegularExpression) } # Argument 'callLoci': callLoci <- Arguments$getLogical(callLoci) # Argument 'callThresholds': callThresholds <- Arguments$getLogical(callThresholds) # Argument 'boundaries': boundaries <- Arguments$getLogical(boundaries) # Argument 'knownSegments': knownSegments <- Arguments$getLogical(knownSegments) # Argument 'add': add <- Arguments$getLogical(add) # Argument 'Clim' & 'Blim': if (!add) { Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) Blim <- Arguments$getNumerics(Blim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Argument 'xlabTicks': if (!is.null(xlabTicks)) { xlabTicks <- Arguments$getCharacter(xlabTicks) } # Argument 'subset': if (!is.null(subset)) { subset <- Arguments$getDouble(subset) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Plotting PSCN tracks") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset by chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!is.null(chromosomes)) { verbose && enter(verbose, "Plotting a subset of the chromosomes") fit <- extractChromosomes(fit, chromosomes=chromosomes, verbose=verbose) verbose && exit(verbose) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- tileChromosomes(fit, verbose=verbose) verbose && str(verbose, fit) # Extract the input data data <- getLocusData(fit) if (is.null(data)) { stop("Cannot plot segmentation results. No input data available.") } # Extract the segmentation segs <- as.data.frame(fit) # Identify available calls callData <- NULL if (!is.null(calls) || callThresholds) { verbose && enter(verbose, "Identifying calls") pattern <- "Call$" allCallColumns <- grep(pattern, colnames(segs), value=TRUE) allCallLabels <- toupper(gsub(pattern, "", allCallColumns)) verbose && cat(verbose, "Call columns:") verbose && print(verbose, allCallColumns) if (!is.null(calls)) { callColumns <- allCallColumns if (length(callColumns) > 0L) { keep <- sapply(calls, FUN=function(pattern) { (regexpr(pattern, callColumns) != -1L) }) if (is.matrix(keep)) { keep <- rowAnys(keep, useNames=FALSE) } callColumns <- callColumns[keep] callLabels <- allCallLabels[keep] # Annotate individual loci by calls? if (callLoci) { callData <- extractCallsByLocus(fit, verbose=less(verbose,5)) } } verbose && cat(verbose, "Call to be annotated:") verbose && print(verbose, callColumns) } verbose && exit(verbose) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset of the loci? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!is.null(subset)) { # (a) Set and unset the random seed if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=%d)\n", seed) } # (b) Subset n <- nrow(data) keep <- sample(n, size=subset*n) data <- data[keep,] if (!is.null(callData)) { callData <- callData[keep,] } } # To please R CMD check CT <- rho <- muN <- betaT <- betaN <- betaTN <- rho <- NULL rm(list=c("CT", "rho", "muN", "betaT", "betaN", "betaTN")) attachLocally(data) # Calculate (C1,C2) C1 <- 1/2*(1-rho)*CT C2 <- CT - C1 # BACKWARD COMPATIBILITY: # If 'rho' is not available, recalculate it from tumor BAFs. # NOTE: This should throw an error in the future. /HB 2013-10-25 if (is.null(data$rho)) { isSnp <- (!is.na(betaTN) & !is.na(muN)) isHet <- isSnp & (muN == 1/2) rho <- rep(NA_real_, times=nbrOfLoci) rho[isHet] <- 2*abs(betaTN[isHet]-1/2) warning(sprintf("Locus-level DH signals ('rho') were not available in the %s object and therefore recalculated from the TumorBoost-normalized tumor BAFs ('betaTN').", class(fit)[1L])) } x <- xScale * x vs <- xScale * fit$chromosomeStats[,1:2,drop=FALSE] mids <- (vs[,1]+vs[,2])/2 nbrOfLoci <- length(x) chrTags <- sprintf("Chr%02d", chromosomes) if (subplots) { subplots(length(tracks), ncol=1L) par(oma=oma, mar=mar) } pchT <- if (!is.null(scatter)) { pch } else { NA } xlim <- range(x, na.rm=TRUE) xlab <- "Genomic position" # Graphical handle gh <- list(fit=fit) gh$xScale <- xScale gh$xlim <- xlim gh$xlab <- xlab if (!is.null(callData)) { gh$callsByLocus <- callData } for (tt in seq_along(tracks)) { track <- tracks[tt] verbose && enter(verbose, sprintf("Track #%d ('%s') of %d", tt, track, length(tracks))) # Get graphical style parameters. tracksT <- unlist(strsplit(track, split=",", fixed=TRUE)) colS <- sapply(tracksT, FUN=getScatterColor) colL <- sapply(tracksT, FUN=getLevelColor) colC <- sapply(tracksT, FUN=getCIColor) # Color scatter plot according to calls? if (!is.null(calls) && callLoci && length(callColumns) > 0L) { colsT <- rep(colS[1L], times=nrow(callData)) for (cc in seq_along(callColumns)) { callColumn <- callColumns[cc] callLabel <- callLabels[cc] verbose && enter(verbose, sprintf("Call #%d ('%s') of %d", cc, callLabel, length(callColumns))) verbose && cat(verbose, "Column: ", callColumn) skip <- TRUE if (regexpr("tcn", track) != -1L) { skip <- !is.element(callLabel, c("LOSS", "NTCN", "GAIN", "LOH")) } else if (track == "dh") { skip <- !is.element(callLabel, c("AB", "LOH")) } if (skip) { verbose && exit(verbose) next } callsCC <- callData[[callColumn]] idxs <- which(callsCC) # Nothing to do? if (length(idxs) == 0L) { verbose && exit(verbose) next } callCol <- getCallScatterColor(callLabel) colsT[idxs] <- callCol } # for (cc in ...) colS <- colsT } # if (!is.null(calls)) # Assign graphical-handle parameters gh$track <- track gh$subtracks <- tracksT gh$scatter <- list(col=colS, pch=pchT) gh$level <- list(col=colL) gh$cis <- list(col=colC) if (track == "tcn") { plot(NA, xlim=xlim, ylim=Clim, xlab=xlab, ylab="TCN", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) if (!is.na(pchT)) { points(x, CT, pch=pchT, col=colS) } drawConfidenceBands(fit, what="tcn", quantiles=quantiles, col=colC["tcn"], xScale=xScale) drawLevels(fit, what="tcn", col=colL, xScale=xScale) } if (is.element(track, c("tcn,c1,c2", "c1,c2", "c1", "c2"))) { tracksT <- unlist(strsplit(track, split=",", fixed=TRUE)) plot(NA, xlim=xlim, ylim=Clim, xlab=xlab, ylab="C1, C2, TCN", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) # Draw scatter for TCN or C1 and C2. if (!is.na(pchT)) { if (is.element("tcn", tracksT)) { points(x, CT, pch=pchT, col=colS) } else { if (is.element("c1", tracksT)) { points(x, C1, pch=pchT, col=colS) } if (is.element("c2", tracksT)) { points(x, C2, pch=pchT, col=colS) } } } # Draw confidence bands for TCN, C1, C2. if (is.element("tcn", tracksT)) { drawConfidenceBands(fit, what="tcn", quantiles=quantiles, col=colC["tcn"], xScale=xScale) } if (is.element("c2", tracksT)) { drawConfidenceBands(fit, what="c2", quantiles=quantiles, col=colC["c2"], xScale=xScale) } if (is.element("c1", tracksT)) { drawConfidenceBands(fit, what="c1", quantiles=quantiles, col=colC["c1"], xScale=xScale) } # Draw segment means for TCN, C1, C2. if (is.element("tcn", tracksT)) { drawLevels(fit, what="tcn", col=colL["tcn"], xScale=xScale) } if (is.element("c2", tracksT)) { drawLevels(fit, what="c2", col=colL["c2"], xScale=xScale) } if (is.element("tcn", tracksT)) { # In case C2 overlaps with TCN drawLevels(fit, what="tcn", col=colL["tcn"], lty="22", xScale=xScale) } # In case C1 overlaps with C2 if (is.element("c1", tracksT)) { drawLevels(fit, what="c1", col=colL["c1"], xScale=xScale) if (is.element("c2", tracksT)) { drawLevels(fit, what="c2", col=colL["c2"], lty="22", xScale=xScale) } if (is.element("tcn", tracksT)) { drawLevels(fit, what="tcn", col=colL["tcn"], lty="22", xScale=xScale) } } } if (track == "betaN") { plot(NA, xlim=xlim, ylim=Blim, xlab=xlab, ylab="BAF_N", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) if (!is.na(pchT)) { points(x, betaN, pch=pchT, col=colS) } } if (track == "betaT") { plot(NA, xlim=xlim, ylim=Blim, xlab=xlab, ylab="BAF_T", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) if (!is.na(pchT)) { points(x, betaT, pch=pchT, col=colS) } } if (track == "betaTN") { plot(NA, xlim=xlim, ylim=Blim, xlab=xlab, ylab="BAF_TN", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) if (!is.na(pchT)) { points(x, betaTN, pch=pchT, col=colS) } } if (track == "dh") { plot(NA, xlim=xlim, ylim=Blim, xlab=xlab, ylab="DH", axes=FALSE) if (!is.null(onBegin)) attachGH(onBegin(gh=gh)) if (!is.na(pchT)) { points(x, rho, pch=pchT, col=colS) } drawConfidenceBands(fit, what="dh", quantiles=quantiles, col=colC["dh"], xScale=xScale) drawLevels(fit, what="dh", col=colL["dh"], xScale=xScale) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each panel of tracks, annotate segments with calls? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!is.null(calls) && !callLoci && length(callColumns) > 0L) { for (cc in seq_along(callColumns)) { callColumn <- callColumns[cc] callLabel <- callLabels[cc] verbose && enter(verbose, sprintf("Call #%d ('%s') of %d", cc, callLabel, length(callColumns))) verbose && cat(verbose, "Column: ", callColumn) segsT <- segs[,c("dhStart", "dhEnd", callColumn)] isCalled <- which(segsT[[callColumn]]) segsT <- segsT[isCalled,1:2,drop=FALSE] verbose && printf(verbose, "Number of segments called %s: %d\n", callLabel, nrow(segsT)) segsT <- xScale * segsT verbose && str(verbose, segsT) side <- 2*((cc+1) %% 2) + 1 # For each segment called... for (ss in seq_len(nrow(segsT))) { x0 <- segsT[ss,1,drop=TRUE] x1 <- segsT[ss,2,drop=TRUE] abline(v=c(x0,x1), lty=3, col="gray") xMid <- (x0+x1)/2 mtext(side=side, at=xMid, line=-1, cex=0.7, col="#666666", callLabel) } # for (ss in ...) verbose && exit(verbose) } # for (cc in ...) } # if (!is.null(calls)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each panel of tracks, annotate with call thresholds? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (callThresholds) { # Add call parameter estimates, e.g. deltaAB colCL <- sapply(tracksT, FUN=getCallLevelColor) ltyCL <- sapply(tracksT, FUN=getCallLevelLty) trackT <- track for (cc in seq_along(allCallColumns)) { callColumn <- allCallColumns[cc] callLabel <- allCallLabels[cc] h <- NULL if (callLabel == "AB") { if (track == "dh") { h <- fit$params$deltaAB label <- expression(Delta[AB]) } } else if (callLabel == "LOH") { if (regexpr("c1", track) != -1L) { h <- fit$params$deltaLowC1 label <- expression(Delta[LOH]) trackT <- "c1" } } else if (callLabel == "NTCN") { if (track == "tcn") { h <- fit$params$ntcnRange label <- c(expression(Delta[-NTCN]), expression(Delta[+NTCN])) } } if (!is.null(h)) { abline(h=h, lty=ltyCL[trackT], lwd=2, col=colCL[trackT]) for (ss in 1:2) { side <- c(2,4)[ss] adj <- c(1.2,-0.2)[ss] mtext(side=side, at=h, label, adj=adj, las=2, xpd=TRUE) } } } # for (cc in ...) } # if (callThresholds) drawXLabelTicks() if (boundaries) { abline(v=vs, lty=1, lwd=2) } if (knownSegments) { colT <- getKnownSegmentColor() ltyT <- getKnownSegmentLty() drawKnownSegments(fit, col=colT, lty=ltyT) } axis(side=2); box() if (!is.null(onEnd)) onEnd(gh=gh) verbose && exit(verbose) } # for (tt ...) verbose && exit(verbose) invisible(gh) }, private=TRUE) # plotTracksManyChromosomes() PSCBS/R/installDNAcopy.R0000644000176200001440000000333314564051545014347 0ustar liggesusers############################################################################/** # @RdocDefault installDNAcopy # # @title "Install the DNAcopy package" # # @synopsis # # \description{ # @get "title", if missing. # } # # \arguments{ # \item{...}{Arguments passed to the install function.} # \item{force}{If @FALSE and the \pkg{DNAcopy} package is already # installed, then it will not be re-install. # If @TRUE, it will be installed.} # } # # \value{ # Returns nothing. # } # # \details{ # This function is will download and call the \code{biocLite()} # installation function from the Bioconductor Project website. # This function will also make sure that \pkg{DNAcopy} is loaded so # that it is reported by @see "utils::sessionInfo". # } # # @author "HB" # # @keyword internal #*/############################################################################ setMethodS3("installDNAcopy", "default", function(..., force=FALSE) { # Argument 'force': force <- Arguments$getLogical(force) # Package to be installed pkgName <- "DNAcopy" # Is DNAcopy already available? if (!force && isPackageInstalled(pkgName)) { library(pkgName, character.only=TRUE) return(invisible()) } # If not, install it... if (getRversion() >= "3.5.0") { if (!isPackageInstalled("BiocManager")) install.packages("BiocManager") ns <- getNamespace("BiocManager") BiocManager_install <- get("install", envir = ns) BiocManager_install(pkgName, ...) } else { # To please R CMD check biocLite <- NULL; rm(list="biocLite") source("https://www.bioconductor.org/biocLite.R") biocLite(pkgName, ...) } # ...and load it library(pkgName, character.only=TRUE) return(invisible()) }) # installDNAcopy() PSCBS/R/zzz.R0000644000176200001440000000141014564051545012312 0ustar liggesusers.use <- function(name, package, ..., mode = "function") { get(name, mode = mode, envir = getNamespace(package)) } .onLoad <- function(libname, pkgname) { ## covr: skip=5 ns <- getNamespace(pkgname) pkg <- Package(pkgname) # Assign '.PSCBS' object [since 'PSCBS' is a constructor/Class]. name <- sprintf(".%s", pkgname) assign(name, pkg, envir = ns, inherits = FALSE) } .onAttach <- function(libname, pkgname) { # Copy some pre-memoized CBS-parameter calculations to the 'R.cache' # cache. This speeds up the calculation for common CBS use cases. .prememoize() # Get '.PSCBS' object [since 'PSCBS' is a constructor/Class]. name <- sprintf(".%s", pkgname) pkg <- get(name, envir = getNamespace(pkgname), inherits = FALSE) startupMessage(pkg) } PSCBS/R/DNAcopy.EXTS.R0000644000176200001440000001426215000272374013534 0ustar liggesusers###########################################################################/** # @set class=CBS # @RdocMethod as.DNAcopy # # @title "Coerces a CBS object to a DNAcopy object" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{fit}{A @see "CBS" object."} # \item{...}{Not used.} # } # # \value{ # Returns a \code{\link[DNAcopy:DNAcopy]{DNAcopy}} object # (of the \pkg{DNAcopy} package). # } # # \examples{ # @include "../incl/segmentByCBS.Rex" # @include "../incl/as.DNAcopy.Rex" # } # # @author "HB" # # \seealso{ # \code{\link[PSCBS:as.CBS.DNAcopy]{as.CBS()}}. # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("as.DNAcopy", "CBS", function(fit, ...) { sampleName <- getSampleName(fit) if (is.na(sampleName)) sampleName <- "" # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup the 'data' field # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) # Keep only certain columns keep <- match(c("chromosome", "x"), colnames(data)) keep <- c(keep, 3L) data <- data[,keep,drop=FALSE] # Sanity check .stop_if_not(ncol(data) == 3) # Rename column names colnames(data) <- c("chrom", "maploc", sampleName) class(data) <- c("CNA", "data.frame") attr(data, "data.type") <- "logratio" # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup the 'output' field # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - output <- getSegments(fit, splitters=FALSE) rownames <- rownames(output) output <- data.frame( ID = sampleName, chrom = output$chromosome, loc.start = output$start, loc.end = output$end, num.mark = output$nbrOfLoci, seg.mean = output$mean, stringsAsFactors=FALSE ) rownames(output) <- rownames # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup up 'DNAcopy' object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - res <- list() res$data <- data res$output <- output res$call <- NA class(res) <- "DNAcopy" res }, protected=TRUE) # as.DNAcopy() setMethodS3("nbrOfSegments", "DNAcopy", function(fit, ...) { segs <- fit$output nrow(segs) }) setMethodS3("nbrOfLoci", "DNAcopy", function(fit, ...) { nrow(fit$data) }) setMethodS3("nbrOfSamples", "DNAcopy", function(fit, ...) { length(getSampleNames(fit, ...)) }) setMethodS3("getSampleNames", "DNAcopy", function(fit, ...) { names <- colnames(fit$data) names <- setdiff(names, c("chrom", "maploc")) names }) setMethodS3("getChromosomes", "DNAcopy", function(fit, ...) { chromosomes <- fit$data$chrom sort(unique(chromosomes)) }) setMethodS3("estimateStandardDeviation", "DNAcopy", function(fit, sample=1L, method=c("diff", "abs", "res"), estimator=c("mad", "sd"), na.rm=TRUE, weights=NULL, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'sample': sample <- Arguments$getIndex(sample, max=nbrOfSamples(fit)) # Argument 'method': method <- match.arg(method) # Argument 'estimator': estimator <- match.arg(estimator) nbrOfLoci <- nbrOfLoci(fit) # Argument 'weights': if (!is.null(weights)) { weights <- Arguments$getNumerics(weights, range=c(0,Inf), length=rep(nbrOfLoci, times=2)) } # Nothing to do? if (nbrOfLoci <= 1) { return(NA_real_) } # Get the estimator function if (!is.null(weights)) { estimator <- sprintf("weighted %s", estimator) estimator <- R.utils::toCamelCase(estimator) } estimatorFcn <- get(estimator, mode="function") # Extract sample of interest fit <- subset(fit, samplelist=sample) y <- fit$data[,3L] if (method == "diff") { y <- diff(y) # Weighted estimator? if (!is.null(weights)) { # Calculate weights per pair weights <- (weights[1:(nbrOfLoci-1)]+weights[2:nbrOfLoci])/2 sigma <- estimatorFcn(y, w=weights, na.rm=na.rm)/sqrt(2) } else { sigma <- estimatorFcn(y, na.rm=na.rm)/sqrt(2) } } else if (method == "abs") { if (!is.null(weights)) { sigma <- estimatorFcn(y, w=weights, na.rm=na.rm) } else { sigma <- estimatorFcn(y, na.rm=na.rm) } } else if (method == "res") { yS <- extractSegmentMeansByLocus(fit) dy <- y - yS if (!is.null(weights)) { sigma <- estimatorFcn(dy, w=weights, na.rm=na.rm) } else { sigma <- estimatorFcn(dy, na.rm=na.rm) } } else { stop("Method no implemented: ", method) } sigma }) # estimateStandardDeviation() setMethodS3("extractSegmentMeansByLocus", "DNAcopy", function(fit, sample=1L, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'sample': sample <- Arguments$getIndex(sample, max=nbrOfSamples(fit)) # Extract sample of interest fit <- subset(fit, samplelist=sample) data <- fit$data chr <- data$chrom x <- data$maploc y <- data[,sample,drop=TRUE] segs <- fit$output nbrOfSegments <- nrow(segs) nbrOfLoci <- nbrOfLoci(fit) # Get mean estimators estList <- getMeanEstimators(fit, "y") avgY <- estList$y yS <- y for (ss in seq_len(nbrOfSegments)) { seg <- segs[ss,] idxs <- which(seg$chrom == chr & seg$loc.start <= x & x <= seg$loc.end) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) ySS <- y[idxs] ok <- is.finite(ySS) # Sanity check ## .stop_if_not(sum(ok) == seg$num.mark) # Not dealing with ties mu <- avgY(ySS[ok]) yS[idxs] <- mu } # for (ss ...) yS }, private=TRUE) # extractSegmentMeansByLocus() setMethodS3("writeSegments", "DNAcopy", function(fit, samples=seq_len(nbrOfSamples(fit)), ...) { # Argument 'samples': samples <- Arguments$getIndices(samples, max=nbrOfSamples(fit)) pathnames <- c() for (ii in samples) { fitII <- as.CBS(fit, sample=ii) pathnameII <- writeSegments(fitII, ...) pathnames <- c(pathnames, pathnameII) } # for (ii ...) pathnames }) # writeSegments() PSCBS/R/CBS.IO.R0000644000176200001440000001703514564051545012404 0ustar liggesuserssetMethodS3("writeLocusData", "CBS", function(fit, name=getSampleName(fit), tags=NULL, ext="tsv", path=NULL, sep="\t", nbrOfDecimals=4L, addHeader=TRUE, createdBy=NULL, overwrite=FALSE, skip=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'name' and 'tags': name <- Arguments$getCharacter(name) tags <- Arguments$getCharacters(tags) # Argument 'ext': ext <- Arguments$getCharacter(ext) # Arguments 'path': path <- Arguments$getWritablePath(path) # Argument 'nbrOfDecimals': nbrOfDecimals <- Arguments$getInteger(nbrOfDecimals) fullname <- paste(c(name, tags), collapse=",") filename <- sprintf("%s.%s", fullname, ext) pathname <- Arguments$getWritablePathname(filename, path=path, mustNotExist=(!overwrite && !skip)) # File already exists? if (isFile(pathname)) { # Skip? if (skip) { return(pathname) } # Overwrite! file.remove(pathname) } # Write to temporary file pathnameT <- pushTemporaryFile(pathname) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit, ...) # Round of floating points if (!is.null(nbrOfDecimals)) { cols <- colnames(data) for (key in cols) { values <- data[[key]] if (is.double(values)) { values <- round(values, digits=nbrOfDecimals) data[[key]] <- values } } # for (key ...) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Build header # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (addHeader) { sigmaDelta <- estimateStandardDeviation(fit, method="diff") # sigmaResiduals <- estimateStandardDeviation(fit, method="res") createdOn <- format(Sys.time(), format="%Y-%m-%d %H:%M:%S %Z") hdr <- c( name=name, tags=tags, fullname=fullname, segmentationMethod=sprintf("segment() of %s", attr(fit, "pkgDetails")), nbrOfLoci=nbrOfLoci(fit), nbrOfSegments=nbrOfSegments(fit), joinSegments=fit$params$joinSegments, signalType=getSignalType(fit), sigmaDelta=sprintf("%.4f", sigmaDelta), # sigmaResiduals=sprintf("%.4f", sigmaResiduals), createdBy=createdBy, createdOn=createdOn, nbrOfDecimals=nbrOfDecimals, nbrOfColumns=ncol(data), columnNames=paste(colnames(data), collapse=", "), columnClasses=paste(sapply(data, FUN=function(x) class(x)[1]), collapse=", ") ) bfr <- paste("# ", names(hdr), ": ", hdr, sep="") cat(file=pathnameT, bfr, sep="\n") } # if (addHeader) write.table(file=pathnameT, data, append=TRUE, quote=FALSE, sep=sep, row.names=FALSE, col.names=TRUE) pathname <- popTemporaryFile(pathnameT) pathname }, protected=TRUE) # writeLocusData() ###########################################################################/** # @set "class=CBS" # @RdocMethod writeSegments # @alias writeWIG # @alias writeWIG.AbstractCBS # # @title "Writes the table of segments to file" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{name, tags}{Name and optional tags part of the filename}. # \item{path}{The directory where the file will be written.} # \item{addHeader}{If @TRUE, header comments are written.} # \item{createdBy}{A header comment of whom created the file.} # \item{splitters}{If @TRUE, each chromosome is separated by a row # of missing values.} # \item{overwrite, skip}{If an output file already exists, these # arguments specifies what should happen.} # \item{...}{Additional arguments pass to \code{getSegments()}.} # } # # \value{ # Returns the pathname of the the file written. # } # # @author "HB" # # \seealso{ # Utilizes @seemethod "getSegments". # @seeclass. # } # # @keyword internal #*/########################################################################### setMethodS3("writeSegments", "CBS", function(fit, name=getSampleName(fit), tags=NULL, ext="tsv", path=NULL, addHeader=TRUE, createdBy=NULL, sep="\t", nbrOfDecimals=4L, splitters=FALSE, overwrite=FALSE, skip=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'name' and 'tags': name <- Arguments$getCharacter(name) tags <- Arguments$getCharacters(tags) # Argument 'ext': ext <- Arguments$getCharacter(ext) # Arguments 'path': path <- Arguments$getWritablePath(path) # Argument 'nbrOfDecimals': nbrOfDecimals <- Arguments$getInteger(nbrOfDecimals) fullname <- paste(c(name, tags), collapse=",") filename <- sprintf("%s.%s", fullname, ext) pathname <- Arguments$getWritablePathname(filename, path=path, mustNotExist=(!overwrite && !skip)) # File already exists? if (isFile(pathname)) { # Skip? if (skip) { return(pathname) } # Overwrite! file.remove(pathname) } # Write to temporary file pathnameT <- pushTemporaryFile(pathname) sampleName <- getSampleName(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getSegments(fit, ..., splitters=splitters) # Round of floating points if (!is.null(nbrOfDecimals)) { cols <- tolower(colnames(data)) isInt <- (regexpr("chromosome|start|end|nbrofloci", cols) != -1) cols <- which(isInt) for (cc in cols) { values <- data[[cc]] if (is.double(values)) { values <- round(values, digits=0) data[[cc]] <- values } } # for (key ...) cols <- tolower(colnames(data)) isInt <- (regexpr("chromosome|start|end|nbrofloci", cols) != -1) isLog <- (regexpr("call", cols) != -1) isDbl <- (!isInt & !isLog) cols <- which(isDbl) for (kk in cols) { values <- data[[kk]] if (is.double(values)) { values <- round(values, digits=nbrOfDecimals) data[[kk]] <- values } } # for (key ...) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Build header # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (addHeader) { sigmaDelta <- estimateStandardDeviation(fit, method="diff") # sigmaResiduals <- estimateStandardDeviation(fit, method="res") createdOn <- format(Sys.time(), format="%Y-%m-%d %H:%M:%S %Z") hdr <- c( name=name, tags=tags, fullname=fullname, segmentationMethod=sprintf("segment() of %s", attr(fit, "pkgDetails")), nbrOfLoci=nbrOfLoci(fit), nbrOfSegments=nbrOfSegments(fit), joinSegments=fit$params$joinSegments, signalType=getSignalType(fit), sigmaDelta=sprintf("%.4f", sigmaDelta), # sigmaResiduals=sprintf("%.4f", sigmaResiduals), createdBy=createdBy, createdOn=createdOn, nbrOfDecimals=nbrOfDecimals, nbrOfColumns=ncol(data), columnNames=paste(colnames(data), collapse=", "), columnClasses=paste(sapply(data, FUN=function(x) class(x)[1]), collapse=", ") ) bfr <- paste("# ", names(hdr), ": ", hdr, sep="") cat(file=pathnameT, bfr, sep="\n") } # if (addHeader) write.table(file=pathnameT, data, append=TRUE, quote=FALSE, sep=sep, row.names=FALSE, col.names=TRUE) pathname <- popTemporaryFile(pathnameT) pathname }) # writeSegments() PSCBS/R/PairedPSCBS.updateMeansTogether.R0000644000176200001440000000611314564051545017430 0ustar liggesuserssetMethodS3("updateMeansTogether", "PairedPSCBS", function(fit, idxList, ..., avgTCN=c("mean", "median"), avgDH=c("mean", "median"), verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(fit, splitters=TRUE) # Argument 'idxList': if (!is.list(idxList)) { idxList <- list(idxList) } idxList <- lapply(idxList, FUN=function(idxs) { idxs <- Arguments$getIndices(idxs, max=nbrOfSegments) sort(unique(idxs)) }) # Argument 'avgTCN' & 'avgDH': avgTCN <- match.arg(avgTCN) avgDH <- match.arg(avgDH) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating mean level estimates of multiple segments") verbose && cat(verbose, "Segments:") verbose && str(verbose, idxList) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up averaging functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - avgList <- list( tcn = get(avgTCN, mode="function"), dh = get(avgDH, mode="function") ) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit, splitters=TRUE) nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Total number of segments: ", nbrOfSegments) for (ss in seq_along(idxList)) { idxs <- idxList[[ss]] fitT <- extractSegments(fit, idxs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fitT)) dataT <- getLocusData(fitT) segsT <- getSegments(fitT) CT <- dataT$CT rho <- dataT$rho # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update the TCN segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Recalculate (TCN,DH,C1,C2) means") naValue <- NA_real_ mus <- c(tcn=naValue, dh=naValue, c1=naValue, c2=naValue) for (key in c("tcn", "dh")) { avgFUN <- avgList[[key]] # (c) Adjust for missing values if (key == "tcn") { value <- CT } else if (key == "dh") { value <- rho } keep <- which(!is.na(value)) # (d) Update mean gamma <- avgFUN(value[keep]) # Sanity check .stop_if_not(length(gamma) == 0 || !is.na(gamma)) mus[key] <- gamma } # for (what ...) mus["c1"] <- 1/2*(1-mus["dh"])*mus["tcn"] mus["c2"] <- mus["tcn"] - mus["c1"] names(mus) <- sprintf("%sMean", names(mus)) verbose && print(verbose, mus) verbose && exit(verbose) for (key in names(mus)) { segs[idxs,key] <- mus[key] } } # for (ss ...) # Return results res <- fit res$output <- segs res <- setMeanEstimators(res, tcn=avgTCN, dh=avgDH) verbose && exit(verbose) res }, private=TRUE) # updateMeansTogether() PSCBS/R/writeWIG.R0000644000176200001440000000774414564051545013176 0ustar liggesuserssetMethodS3("extractWIG", "AbstractCBS", function(fit, signal, transform=NULL, nbrOfDecimals=4L, label=toupper(signal), graphType=c("bar", "points", "line"), viewLimits=NULL, colors=c(negative="231,41,138", positive="117,112,179"), ...) { # Argument 'graphType': graphType <- match.arg(graphType) # Argument 'nbrOfDecimals': nbrOfDecimals <- Arguments$getInteger(nbrOfDecimals) data <- getSegments(fit, splitters=FALSE) fields <- c("chromosome", "start", "end", "mean") if (!is.null(signal)) { fields[-1] <- sprintf("%s%s", signal, capitalize(fields[-1])) } data <- data[,fields] colnames(data) <- c("chromosome", "start", "end", "mean") data$chromosome <- sprintf("chr%d", data$chromosome) ## Round / truncate for (ff in c("start", "end")) { data[[ff]] <- as.integer(round(data[[ff]], digits=0L)) } # Transform mean levels? if (!is.null(transform)) { data[["mean"]] <- transform(data[["mean"]]) } # Round mean levels if (!is.null(nbrOfDecimals)) { data[["mean"]] <- round(data[["mean"]], digits=nbrOfDecimals) } # Drop segments with missing values data <- na.omit(data) ## Track information track <- list( type="wiggle_0", name=sampleName(fit), description=sprintf("Data type: %s", class(fit)), graphType=graphType, visibility="full", maxHeightPixels="128:96:64", yLineOnOff="on", autoScale="true" ) if (is.na(track$name)) track$name <- "Unknown sample" if (!is.null(signal)) track$name <- sprintf("%s [%s]", track$name, label) if (!is.null(viewLimits)) { track$viewLimits <- sprintf("%g:%g", viewLimits[1], viewLimits[2]) } if (!is.null(colors)) { if (!is.null(names(colors))) colors <- colors[c("negative", "positive")] track$color <- colors[["negative"]] track$altColor <- colors[["positive"]] } attr(data, "track") <- track data }, protected=TRUE) setMethodS3("extractWIG", "CBS", function(fit, ..., colors=c(negative="231,41,138", positive="117,112,179")) { NextMethod("extractWIG", signal=NULL, colors=colors) }, protected=TRUE) setMethodS3("extractWIG", "PSCBS", function(fit, signal=c("tcn", "dh"), ..., colors=c(negative="231,41,138", positive="117,112,179")) { signal <- match.arg(signal) NextMethod("extractWIG", signal=signal, colors=colors) }, protected=TRUE) # \references{ # [1] Wiggle Track Format (WIG), UCSC Genome Browser # \url{https://genome.ucsc.edu/goldenPath/help/wiggle.html} # } setMethodS3("writeWIG", "AbstractCBS", function(fit, name=getSampleName(fit), tags=NULL, ext="wig", path=NULL, overwrite=FALSE, skip=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'name' and 'tags': name <- Arguments$getCharacter(name) tags <- Arguments$getCharacters(tags) # Argument 'ext': ext <- Arguments$getCharacter(ext) # Arguments 'path': path <- Arguments$getWritablePath(path) fullname <- paste(c(name, tags), collapse=",") filename <- sprintf("%s.%s", fullname, ext) pathname <- Arguments$getWritablePathname(filename, path=path, mustNotExist=(!overwrite && !skip)) # File already exists? if (isFile(pathname)) { # Skip? if (skip) { return(pathname) } # Overwrite! file.remove(pathname) } ## Write file (atomically) pathnameT <- pushTemporaryFile(pathname) bed <- extractWIG(fit, ...) ## Generate 'track' definition line track <- attr(bed, "track") track <- lapply(track, FUN=function(value) { if (is.character(value)) value <- dQuote(value) value }) track <- unlist(track, use.names=TRUE) track <- sprintf("%s=%s", names(track), track) track <- paste(track, collapse=" ") track <- sprintf("track %s", track) cat(track, "\n", sep="", file=pathnameT) write.table(bed, file=pathnameT, col.names=FALSE, row.names=FALSE, sep="\t", quote=FALSE, append=TRUE) pathname <- popTemporaryFile(pathnameT) pathname }) PSCBS/R/segmentByPairedPSCBS.R0000644000176200001440000013072215000476724015337 0ustar liggesusers###########################################################################/** # @RdocDefault segmentByPairedPSCBS # @alias segmentByPairedPSCBS.data.frame # @alias segmentByPairedPSCBS.PairedPSCBS # @alias segmentByPairedPSCBS # # @title "Segment total copy numbers and allele B fractions using the Paired PSCBS method" # # \description{ # @get "title" [1]. # This method requires matched normals. # This is a low-level segmentation method. # It is intended to be applied to one tumor-normal sample at the time. # } # # @synopsis # # \arguments{ # \item{CT}{A @numeric @vector of J tumor total copy number (TCN) # ratios in [0,+@Inf) (due to noise, small negative values are # also allowed). The TCN ratios are typically scaled such that # copy-neutral diploid loci have a mean of two.} # \item{thetaT, thetaN}{(alternative) As an alternative to specifying # tumor TCN \emph{ratios} relative to the match normal by # argument \code{CT}, on may specify total tumor and normal # signals seperately, in which case the TCN ratios \code{CT} are # calculated as \eqn{CT = 2*thetaT/thetaN}.} # \item{betaT}{A @numeric @vector of J tumor allele B fractions (BAFs) # in [0,1] (due to noise, values may be slightly outside as well) # or @NA for non-polymorphic loci.} # \item{betaN}{A @numeric @vector of J matched normal BAFs in [0,1] # (due to noise, values may be slightly outside as well) or @NA # for non-polymorphic loci.} # \item{muN}{An optional @numeric @vector of J genotype calls in # \{0,1/2,1\} for AA, AB, and BB, respectively, # and @NA for non-polymorphic loci. # If not given, they are estimated from the normal BAFs using # @see "aroma.light::callNaiveGenotypes" as described in [2].} # \item{rho}{(alternative to \code{betaT} and \code{betaN}/\code{muN}) # A @numeric @vector of J decrease-of-heterozygosity signals (DHs) # in [0,1] (due to noise, values may be slightly larger than one # as well). By definition, DH should be @NA for homozygous loci # and for non-polymorphic loci.} # \item{chromosome}{(Optional) An @integer scalar (or a @vector of length J), # which can be used to specify which chromosome each locus belongs to # in case multiple chromosomes are segments. # This argument is also used for annotation purposes.} # \item{x}{Optional @numeric @vector of J genomic locations. # If @NULL, index locations \code{1:J} are used.} # \item{alphaTCN, alphaDH}{The significance levels for segmenting total # copy numbers (TCNs) and decrease-in-heterozygosity signals (DHs), # respectively.} # \item{undoTCN, undoDH}{Non-negative @numerics. If greater than 0, # then a cleanup of segmentions post segmentation is done. # See argument \code{undo} of @see "segmentByCBS" for more # details.} # \item{avgTCN, avgDH}{A @character string specifying how to calculating # segment mean levels \emph{after} change points have been # identified.} # \item{...}{Additional arguments passed to @see "segmentByCBS".} # \item{flavor}{A @character specifying what type of segmentation and # calling algorithm to be used.} # \item{tbn}{If @TRUE, \code{betaT} is normalized before segmentation # using the TumorBoost method [2], otherwise not.} # \item{joinSegments}{If @TRUE, there are no gaps between neighboring # segments. # If @FALSE, the boundaries of a segment are defined by the support # that the loci in the segments provides, i.e. there exist a locus # at each end point of each segment. This also means that there # is a gap between any neighboring segments, unless the change point # is in the middle of multiple loci with the same position. # The latter is what \code{DNAcopy::segment()} returns. # } # \item{knownSegments}{Optional @data.frame specifying # \emph{non-overlapping} known segments. These segments must # not share loci. See @see "findLargeGaps" and @see "gapsToSegments".} # \item{dropMissingCT}{If @TRUE, loci for which 'CT' is missing # are dropped, otherwise not.} # \item{seed}{An (optional) @integer specifying the random seed to be # set before calling the segmentation method. The random seed is # set to its original state when exiting. If @NULL, it is not set.} # \item{verbose}{See @see "R.utils::Verbose".} # \item{preserveScale}{\emph{Defunct - gives an error is specified.}} # } # # \value{ # Returns the segmentation results as a @see "PairedPSCBS" object. # } # # \details{ # Internally @see "segmentByCBS" is used for segmentation. # The Paired PSCBS segmentation method does \emph{not} support weights. # } # # \section{Reproducibility}{ # The "DNAcopy::segment" implementation of CBS uses approximation # through random sampling for some estimates. Because of this, # repeated calls using the same signals may result in slightly # different results, unless the random seed is set/fixed. # } # # \section{Whole-genome segmentation is preferred}{ # Although it is possible to segment each chromosome independently # using Paired PSCBS, we strongly recommend to segment whole-genome # (TCN,BAF) data at once. The reason for this is that downstream # CN-state calling methods, such as the AB and the LOH callers, # performs much better on whole-genome data. In fact, they may # fail to provide valid calls if done chromosome by chromosome. # } # # \section{Missing and non-finite values}{ # The total copy number signals as well as any optional positions # must not contain missing values, i.e. @NAs or @NaNs. # If there are any, an informative error is thrown. # Allele B fractions may contain missing values, because such are # interpreted as representing non-polymorphic loci. # # None of the input signals may have infinite values, i.e. -@Inf or +@Inf. # If so, an informative error is thrown. # } # # \section{Paired PSCBS with only genotypes}{ # If allele B fractions for the matched normal (\code{betaN}) are # not available, but genotypes (\code{muN}) are, then it is possible # to run a version of Paired PSCBS where TumorBoost normalization # of the tumor allele B fractions is skipped. In order for this # to work, argument \code{tbn} must be set to @FALSE. # } # # @examples "../incl/segmentByPairedPSCBS.Rex" # # @author "HB" # # \references{ # [1] @include "../incl/OlshenA_etal_2011.Rd" \cr # [2] @include "../incl/BengtssonH_etal_2010.Rd" \cr # } # # \seealso{ # Internally, @see "aroma.light::callNaiveGenotypes" is used to # call naive genotypes, @see "aroma.light::normalizeTumorBoost" is # used for TumorBoost normalization, and @see "segmentByCBS" is used # to segment TCN and DH separately. # # To segment tumor total copy numbers and allele B fractions # \emph{without} a matched normal, see @see "segmentByNonPairedPSCBS". # # To segment total copy-numbers, or any other unimodal signals, # see @see "segmentByCBS". # } # # @keyword IO #*/########################################################################### setMethodS3("segmentByPairedPSCBS", "default", function(CT, thetaT=NULL, thetaN=NULL, betaT=NULL, betaN=NULL, muN=NULL, rho=NULL, chromosome=0, x=NULL, alphaTCN=0.009, alphaDH=0.001, undoTCN=0, undoDH=0, ..., avgTCN=c("mean", "median"), avgDH=c("mean", "median"), flavor=c("tcn&dh", "tcn,dh", "sqrt(tcn),dh", "sqrt(tcn)&dh", "tcn"), tbn=is.null(rho), joinSegments=TRUE, knownSegments=NULL, dropMissingCT=TRUE, seed=NULL, verbose=FALSE, preserveScale=FALSE) { # WORKAROUND: If Hmisc is loaded after R.utils, it provides a buggy # capitalize() that overrides the one we want to use. Until PSCBS # gets a namespace, we do the following workaround. /HB 2011-07-14 capitalize <- R.utils::capitalize # To please R CMD check index <- NULL; rm(list="index") # Settings for sanity checks tol <- getOption("PSCBS/sanityChecks/tolerance", 0.0005) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'thetaT' & 'thetaN': if (!is.null(thetaT) && !is.null(thetaN)) { thetaT <- Arguments$getDoubles(thetaT, disallow=disallow) nbrOfLoci <- length(thetaT) length2 <- rep(nbrOfLoci, times=2L) thetaN <- Arguments$getDoubles(thetaN, length=length2, disallow=disallow) CT <- 2 * thetaT / thetaN } else if (!is.null(thetaT) || !is.null(thetaN)) { stop("Either argument 'CT' needs to be specified or *both* of arguments 'thetaT' and 'thetaN'") } # Argument 'CT': disallow <- c("Inf") CT <- Arguments$getDoubles(CT, disallow=disallow) nbrOfLoci <- length(CT) length2 <- rep(nbrOfLoci, times=2L) # Argument 'betaT': if (!is.null(betaT)) { betaT <- Arguments$getDoubles(betaT, length=length2, disallow="Inf") } # Argument 'betaN': if (!is.null(betaN)) { betaN <- Arguments$getDoubles(betaN, length=length2, disallow="Inf") } # Argument 'muN': if (!is.null(muN)) { muN <- Arguments$getDoubles(muN, length=length2, range=c(0,1), disallow="Inf") if (all(is.na(muN)) == nbrOfLoci) { stop(sprintf("All genotypes ('muN') are NAs: %d (100%%) out of %d", nbrOfLoci, nbrOfLoci)) } } # Argument 'rho': if (!is.null(rho)) { rho <- Arguments$getDoubles(rho, range=c(0,Inf), length=length2, disallow="Inf") } if (is.null(muN)) { if (is.null(betaN) && is.null(rho)) { stop("If argument 'muN' is not given, then either 'betaN' or 'rho' must be.") } } # Argument 'tbn': tbn <- Arguments$getLogical(tbn) if (!is.null(tbn)) { if (tbn) { if (is.null(betaT)) { stop("Cannot do TumorBoost normalization (tbn=TRUE) without tumor BAFs ('betaT').") } if (is.null(betaN)) { stop("Cannot do TumorBoost normalization (tbn=TRUE) with normal BAFs ('betaN').") } } } # Argument 'chromosome': if (is.null(chromosome)) { chromosome <- 0L } else { disallow <- c("Inf") chromosome <- Arguments$getIntegers(chromosome, range=c(0,Inf), disallow=disallow) if (length(chromosome) > 1) { chromosome <- Arguments$getIntegers(chromosome, length=length2, disallow=disallow) } } # Argument 'x': if (is.null(x)) { x <- seq_len(nbrOfLoci) } else { disallow <- c("Inf") x <- Arguments$getDoubles(x, length=length2, disallow=disallow) } # Argument 'alphaTCN': alphaTCN <- Arguments$getDouble(alphaTCN, range=c(0,1)) # Argument 'alphaDH': alphaDH <- Arguments$getDouble(alphaDH, range=c(0,1)) # Argument 'undoTCN': undoTCN <- Arguments$getDouble(undoTCN, range=c(0,Inf)) # Argument 'undoDH': undoDH <- Arguments$getDouble(undoDH, range=c(0,Inf)) # Argument 'avgTCN' & 'avgDH': avgTCN <- match.arg(avgTCN) avgDH <- match.arg(avgDH) # Argument 'flavor': flavor <- match.arg(flavor) knownFlavors <- eval(formals(segmentByPairedPSCBS.default)$flavor, enclos = baseenv()) if (!is.element(flavor, knownFlavors)) { stop("Segmentation flavor is not among the supported ones (", paste(sprintf("\"%s\"", knownFlavors), collapse=", "), "): ", flavor) } # Argument 'joinSegments': joinSegments <- Arguments$getLogical(joinSegments) # Argument 'knownSegments': if (is.null(knownSegments)) { knownSegments <- data.frame(chromosome=integer(0), start=integer(0), end=integer(0)) } else { if (!joinSegments) { ## warning("Argument 'knownSegments' should only be specified if argument 'joinSegments' is TRUE.") } } if (!is.data.frame(knownSegments)) { stop("Argument 'knownSegments' is not a data.frame: ", class(knownSegments)[1]) } if (!all(is.element(c("chromosome", "start", "end"), colnames(knownSegments)))) { stop("Argument 'knownSegments' does not have the required column names: ", hpaste(colnames(knownSegments))) } # Argument 'dropMissingCT': dropMissingCT <- Arguments$getLogical(dropMissingCT) if (!dropMissingCT) { if (is.element(flavor, c("tcn&dh", "sqrt(tcn)&dh"))) { stop("Missing values in 'CT' are (currently) not supported by the chosen 'flavor': ", flavor) } } # Argument 'seed': if (!is.null(seed)) { seed <- Arguments$getIntegers(seed) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # Argument 'preserveScale' is deprecated if (!missing(preserveScale)) { .Defunct(msg = "Argument 'preserveScale' for segmentByPairedPSCBS() is defunct; as of PSCBS 0.64.0 (Mar 2018) it is effectively fixed to FALSE, which has been the default since PSCBS 0.50.0 (Oct 2015). To avoid this error, do not specify 'preserveScale' when calling segmentByPairedPSCBS().") } verbose && enter(verbose, "Segmenting paired tumor-normal signals using Paired PSCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call genotypes? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Are genotype calls muN missing and can they be called? if (is.null(muN) && !is.null(betaN)) { verbose && enter(verbose, "Calling genotypes from normal allele B fractions") verbose && str(verbose, betaN) muN <- callNaiveGenotypes(betaN, censorAt=c(0,1)) verbose && cat(verbose, "Called genotypes:") verbose && str(verbose, muN) verbose && print(verbose, table(muN)) # Assert proper calls muN <- Arguments$getDoubles(muN, length=length2, range=c(0,1), disallow="Inf") # Sanity check if (all(is.na(muN))) { stop(sprintf("All genotypes ('muN') called from the normal allele B fractions ('betaN') are NAs: %d (100%%) out of %d", nbrOfLoci, nbrOfLoci)) } verbose && exit(verbose) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Normalize betaT using betaN (TumorBoost normalization) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (tbn) { verbose && enter(verbose, "Normalizing betaT using betaN (TumorBoost)") betaTN <- normalizeTumorBoost(betaT=betaT, betaN=betaN, muN=muN, preserveScale=FALSE) verbose && cat(verbose, "Normalized BAFs:") verbose && str(verbose, betaTN) # Assert that no missing values where introduced keep <- (is.finite(betaT) & is.finite(betaN) & is.finite(muN)) if (anyNA(betaTN[keep])) { stop("Internal error: normalizeTumorBoost() introduced missing values.") } # Not needed anymore keep <- NULL verbose && exit(verbose) } else { betaTN <- betaT } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Setup up data") data <- data.frame(chromosome=chromosome, x=x, CT=CT) if (!is.null(thetaT)) { data$thetaT <- thetaT data$thetaN <- thetaN } if (!is.null(betaT)) data$betaT <- betaT if (!is.null(betaTN)) data$betaTN <- betaTN if (!is.null(betaN)) data$betaN <- betaN if (!is.null(muN)) data$muN <- muN if (!is.null(rho)) data$rho <- rho verbose && str(verbose, data) # Not needed anymore chromosome <- x <- CT <- thetaT <- thetaN <- betaT <- betaTN <- betaN <- muN <- rho <- NULL # Sanity check .stop_if_not(nrow(data) == nbrOfLoci) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop data points without known genomic positions, because that # is what DNAcopy::CNA() will do otherwise. At the end, we will # undo this such that the returned 'data' object is complete. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ok <- (!is.na(data$chromosome) & !is.na(data$x)) if (any(!ok)) { verbose && enter(verbose, "Dropping loci with unknown locations") verbose && cat(verbose, "Number of loci dropped: ", sum(!ok)) data <- data[ok,,drop=FALSE] nbrOfLoci <- nrow(data) verbose && exit(verbose) } ok <- NULL # Not needed anymore # Sanity check .stop_if_not(nrow(data) == nbrOfLoci) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop loci for which CT is missing (regardless of betaT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (dropMissingCT) { ok <- (!is.na(data$CT)) if (any(!ok)) { verbose && enter(verbose, "Dropping loci for which TCNs are missing") verbose && cat(verbose, "Number of loci dropped: ", sum(!ok)) data <- data[ok,,drop=FALSE] nbrOfLoci <- nrow(data) verbose && exit(verbose) } ok <- NULL # Not needed anymore # Sanity check .stop_if_not(nrow(data) == nbrOfLoci) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Reorder data points along the genome, because that is what # DNAcopy::segment() will return. At the end, we will undo # the sort such that the returned 'data' object is always in # the same order and number of loci as the input data. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Ordering data along genome") o <- order(data$chromosome, data$x, decreasing=FALSE, na.last=TRUE) # Any change? if (any(o != seq_along(o))) { data <- data[o,,drop=FALSE] } o <- NULL # Not needed anymore verbose && str(verbose, data) verbose && exit(verbose) # Attach 'index' (guaranteed to be ordered) data$index <- seq_len(nrow(data)) # Sanity check .stop_if_not(nrow(data) == nbrOfLoci) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Assert no missing values in (chromosome, x, CT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity check ok <- (!is.na(data$chromosome) & !is.na(data$x)) if (!all(ok)) { stop("INTERNAL ERROR: Detected (chromosome, x) with missing values also after filtering.") } # Sanity check if (dropMissingCT) { ok <- (!is.na(data$CT)) if (!all(ok)) { stop("INTERNAL ERROR: Detected TCN with missing values also after filtering.") } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multiple chromosomes? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify all chromosomes, excluding missing values chromosomes <- sort(unique(data$chromosome), na.last=NA) nbrOfChromosomes <- length(chromosomes) if (nbrOfChromosomes > 1) { verbose && enter(verbose, "Segmenting multiple chromosomes") verbose && cat(verbose, "Number of chromosomes: ", nbrOfChromosomes) # Generate random seeds? seeds <- NULL if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=c(%s), kind=\"L'Ecuyer-CMRG\")\n", paste(seed, collapse=", ")) seeds <- randomSeed("advance", n=nbrOfChromosomes) verbose && printf(verbose, "Produced %d seeds from this stream for future usage\n", length(seeds)) } fitList <- list() for (kk in seq_len(nbrOfChromosomes)) { chromosomeKK <- chromosomes[kk] chrTag <- sprintf("Chr%02d", chromosomeKK) verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", kk, chrTag, nbrOfChromosomes)) seedKK <- seeds[[kk]] # Extract subset of data and parameters for this chromosome dataKK <- subset(data, chromosome == chromosomeKK) verbose && str(verbose, dataKK) fields <- attachLocally(dataKK, fields=c("CT", "thetaT", "thetaN", "betaT", "betaTN", "betaN", "muN", "rho", "chromosome", "x")) dataKK <- NULL # Not needed anymore knownSegmentsKK <- NULL if (!is.null(knownSegments)) { knownSegmentsKK <- subset(knownSegments, chromosome == chromosomeKK) verbose && cat(verbose, "Known segments:") verbose && print(verbose, knownSegmentsKK) } fitList[[chrTag]] <- future({ fit <- segmentByPairedPSCBS(CT=CT, thetaT=thetaT, thetaN=thetaN, betaT=betaTN, betaN=betaN, muN=muN, rho=rho, chromosome=chromosome, x=x, tbn=FALSE, joinSegments=joinSegments, knownSegments=knownSegmentsKK, alphaTCN=alphaTCN, alphaDH=alphaDH, undoTCN=undoTCN, undoDH=undoDH, avgTCN=avgTCN, avgDH=avgDH, flavor=flavor, ..., seed=seedKK, verbose=verbose) # Sanity checks if (nrow(knownSegmentsKK) == 0) { .stop_if_not(nrow(fit$data) == length(CT)) .stop_if_not(all.equal(fit$data$CT, CT)) .stop_if_not(all.equal(fit$data$muN, muN)) } # Update betaT (which is otherwise equals betaTN) fit$data$betaT <- betaT verbose && print(verbose, head(as.data.frame(fit))) verbose && print(verbose, tail(as.data.frame(fit))) fit }, seed = TRUE, label = sprintf("segmentByPairedPSCBS-%s", chrTag)) rm(list=fields) # Not needed anymore verbose && exit(verbose) } # for (kk ...) verbose && enter(verbose, "Merging (independently) segmented chromosome") fitList <- value(fitList) ## former Reduce() w/ append(..., addSplit = TRUE) fit <- do.call(c, args = c(fitList, addSplit = TRUE)) fitList <- NULL # Not needed anymore verbose && str(verbose, fit) verbose && exit(verbose) # Update parameters that otherwise may be incorrect fit$params$tbn <- tbn fit$params$seed <- seed segs <- as.data.frame(fit) if (nrow(segs) < 6) { verbose && print(verbose, segs) } else { verbose && print(verbose, head(segs)) verbose && print(verbose, tail(segs)) } verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - return(fit) } # if (nbrOfChromosomes > 1) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset 'knownSegments' # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Keeping only current chromosome for 'knownSegments'") currChromosome <- data$chromosome[1] verbose && cat(verbose, "Chromosome: ", currChromosome) knownSegments <- subset(knownSegments, chromosome == currChromosome) nbrOfSegments <- nrow(knownSegments) verbose && cat(verbose, "Known segments for this chromosome:") verbose && print(verbose, knownSegments) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity checks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Here 'knownSegments' should specify at most a single chromosome uChromosomes <- sort(unique(knownSegments$chromosome)) if (length(uChromosomes) > 1) { stop("INTERNAL ERROR: Argument 'knownSegments' specifies more than one chromosome: ", hpaste(uChromosomes)) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Assert no missing values in (chromosome, x, CT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity check ok <- (!is.na(data$chromosome) & !is.na(data$x)) if (!all(ok)) { stop("INTERNAL ERROR: Detected (chromosome, x) with missing values also after filtering.") } # Sanity check if (dropMissingCT) { ok <- (!is.na(data$CT)) if (!all(ok)) { stop("INTERNAL ERROR: Detected TCN with missing values also after filtering.") } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup input data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && cat(verbose, "alphaTCN: ", alphaTCN) verbose && cat(verbose, "alphaDH: ", alphaDH) verbose && cat(verbose, "Number of loci: ", nbrOfLoci) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calculate decrease-of-heterozygosity signals (DHs)? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.null(data$rho)) { verbose && enter(verbose, "Calculating DHs") # SNPs are identifies as those loci that have non-missing 'betaTN' & 'muN' isSnp <- (!is.na(data$betaTN) & !is.na(data$muN)) nbrOfSnps <- sum(isSnp) verbose && cat(verbose, "Number of SNPs: ", nbrOfSnps) # DH is by definition only defined for heterozygous SNPs. # For simplicity, we set it to be NA for non-heterozygous loci. isHet <- isSnp & (data$muN == 1/2) verbose && printf(verbose, "Number of heterozygous SNPs: %d (%.2f%%)\n", sum(isHet), 100*sum(isHet)/nbrOfSnps) rho <- rep(NA_real_, times=nbrOfLoci) rho[isHet] <- 2*abs(data$betaTN[isHet]-1/2) verbose && cat(verbose, "Normalized DHs:") verbose && str(verbose, rho) data$rho <- rho isSnp <- isHet <- rho <- NULL # Not needed anymore verbose && exit(verbose) } ## Sanity check .stop_if_not(!is.null(data$rho)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Generate random seeds? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - seeds <- NULL if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=c(%s), kind=\"L'Ecuyer-CMRG\")\n", paste(seed, collapse=", ")) seeds <- randomSeed("advance", n=2L) ## For TCN and DH names(seeds) <- c("TCN", "DH") verbose && printf(verbose, "Produced %d seeds from this stream for future usage\n", length(seeds)) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # 1a. Identification of change points in total copy numbers # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identification of change points by total copy numbers") fields <- attachLocally(data, fields=c("CT", "thetaT", "thetaN", "chromosome", "x", "index")) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Assert no missing values in (chromosome, x, CT) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity check ok <- (!is.na(data$chromosome) & !is.na(data$x)) if (!all(ok)) { stop("INTERNAL ERROR: Detected (chromosome, x) with missing values also after filtering.") } # Sanity check if (dropMissingCT) { ok <- (!is.na(data$CT)) if (!all(ok)) { stop("INTERNAL ERROR: Detected CT with missing values also after filtering.") } } # Segment TCN ratios # Calculate tumor-normal TCN ratios? fit <- segmentByCBS(CT, chromosome=chromosome, x=x, index=index, joinSegments=joinSegments, knownSegments=knownSegments, alpha=alphaTCN, undo=undoTCN, ..., seed=seeds[["TCN"]], verbose=verbose) verbose && str(verbose, fit) rm(list=fields) # Not needed anymore # Sanity check if (nrow(knownSegments) == 0) { .stop_if_not(nrow(fit$data) == nrow(data)) .stop_if_not(all(fit$data$chromosome == data$chromosome)) .stop_if_not(all(fit$data$x == data$x)) .stop_if_not(all(fit$data$index == data$index)) .stop_if_not(all.equal(fit$data$y, data$CT)) } tcnSegments <- fit$output tcnSegRows <- fit$segRows fit <- NULL # Not needed anymore # Sanity checks .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # 1b. Restructure TCN segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Restructure TCN segmentation results") # Drop dummy columns keep <- setdiff(colnames(tcnSegments), c("sampleName")) tcnSegments <- tcnSegments[,keep,drop=FALSE] # Tag fields by TCN names <- names(tcnSegments) # Adding 'tcn' prefix to column names names <- sprintf("tcn%s", capitalize(names)) names <- gsub("tcnChromosome", "chromosome", names, fixed=TRUE) names(tcnSegments) <- names verbose && print(verbose, tcnSegments) nbrOfSegs <- nrow(tcnSegments) verbose && cat(verbose, "Number of TCN segments: ", nbrOfSegs) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # 2a. Identification of additional change points using DH # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each segment independently, segment decrease of heterozygousity (DH) # using CBS. By definition, only heterozygous SNPs are used. if (flavor == "tcn") { verbose && enter(verbose, "TCN-only segmentation") tcnSegsExpanded <- tcnSegRows dhSegRows <- tcnSegRows # Segments segs <- tcnSegments segs[,"tcnId"] <- seq_len(nbrOfSegs) segs[,"dhId"] <- rep(1L, times=nbrOfSegs) segs[,c("tcnNbrOfSNPs", "tcnNbrOfHets", "dhNbrOfLoci")] <- 0L segs[,"dhStart"] <- segs[,"tcnStart"] segs[,"dhEnd"] <- segs[,"tcnEnd"] # For each TCN segment... for (kk in seq_len(nbrOfSegs)) { tcnId <- kk xStart <- tcnSegments[kk,"tcnStart"] xEnd <- tcnSegments[kk,"tcnEnd"] regionTag <- sprintf("[%10g,%10g]", xStart, xEnd) verbose && enter(verbose, sprintf("Total CN segment #%d (%s) of %d", kk, regionTag, nbrOfSegs)) # Empty segment? rowStart <- tcnSegRows[kk,1] rowEnd <- tcnSegRows[kk,2] # Empty segment or a segment separator? isEmptySegment <- (is.na(rowStart) && is.na(rowEnd)) # Nothing to do? if (isEmptySegment) { verbose && exit(verbose) next } nbrOfTCNLociKK <- tcnSegments[kk,"tcnNbrOfLoci"] verbose && cat(verbose, "Number of TCN loci in segment: ", nbrOfTCNLociKK) rows <- seq(from=rowStart, length.out=nbrOfTCNLociKK) dataKK <- data[rows,,drop=FALSE] nbrOfLociKK <- nrow(dataKK) verbose && cat(verbose, "Locus data for TCN segment:") verbose && str(verbose, dataKK) verbose && cat(verbose, "Number of loci: ", nbrOfLociKK) hasDH <- !is.null(dataKK$rho) if (hasDH) { isSnpKK <- !is.na(dataKK$rho) isHetsKK <- (isSnpKK & (dataKK$rho > 0)) } else { isSnpKK <- !is.na(dataKK$muN) isHetsKK <- (isSnpKK & (dataKK$muN == 1/2)) } nbrOfSnpsKK <- sum(isSnpKK) nbrOfHetsKK <- sum(isHetsKK) verbose && printf(verbose, "Number of SNPs: %d (%.2f%%)\n", nbrOfSnpsKK, 100*nbrOfSnpsKK/nbrOfLociKK) verbose && printf(verbose, "Number of heterozygous SNPs: %d (%.2f%%)\n", nbrOfHetsKK, 100*nbrOfHetsKK/nbrOfSnpsKK) segs[kk,"tcnNbrOfSNPs"] <- nbrOfSnpsKK segs[kk,"tcnNbrOfHets"] <- nbrOfHetsKK segs[kk,"dhNbrOfLoci"] <- nbrOfHetsKK # Adjust 'dhRows[kk,]' rows <- rows[isHetsKK] rows <- range(rows, na.rm=TRUE) dhSegRows[kk,] <- rows # Sanity check if (nbrOfHetsKK > 0) { .stop_if_not(all(dhSegRows[kk,1] <= dhSegRows[kk,2], na.rm=TRUE)) } # Calculate dhMean rhoKK <- dataKK[["rho"]][isHetsKK] segs[kk,"dhMean"] <- mean(rhoKK, na.rm=TRUE) verbose && exit(verbose) } # for (kk ...) # Reorder segmentation columns keys <- c("tcnId", "dhId", colnames(tcnSegments)) keys <- c(keys, setdiff(colnames(segs), keys)) segs <- segs[,keys] verbose && exit(verbose) } else { dhSegRows <- NULL tcnSegsExpanded <- NULL # For each TCN segment... segs <- vector("list", length=nbrOfSegs) for (kk in seq_len(nbrOfSegs)) { tcnId <- kk xStart <- tcnSegments[kk,"tcnStart"] xEnd <- tcnSegments[kk,"tcnEnd"] regionTag <- sprintf("[%10g,%10g]", xStart, xEnd) verbose && enter(verbose, sprintf("Total CN segment #%d (%s) of %d", kk, regionTag, nbrOfSegs)) # Empty segment? rowStart <- tcnSegRows[kk,1] rowEnd <- tcnSegRows[kk,2] # Empty segment or a segment separator? isEmptySegment <- (is.na(rowStart) && is.na(rowEnd)) isSplitter <- (isEmptySegment && is.na(xStart) && is.na(xEnd)) isEmptySegment <- (isEmptySegment & !isSplitter) if (isSplitter) { verbose && cat(verbose, "No signals to segment. Just a \"splitter\" segment. Skipping.") # Sanity check .stop_if_not(kk >= 1) # Add a splitter segment segT <- segs[[kk-1]] segT <- segT[NA_integer_,] keys <- colnames(tcnSegments) segT[,keys] <- tcnSegments[kk,keys] segT[,"tcnId"] <- tcnId segT[,"dhId"] <- 1L segT[,c("tcnNbrOfSNPs", "tcnNbrOfHets", "dhNbrOfLoci")] <- 0L segT[,"dhStart"] <- xStart segT[,"dhEnd"] <- xEnd segs[[kk]] <- segT verbose && print(verbose, segT) # Add a splitter to TCN and DH segment row matrix segRowsT <- dhSegRows[NA_integer_,] dhSegRows <- rbind(dhSegRows, segRowsT) segRowsT <- tcnSegsExpanded[NA_integer_,] tcnSegsExpanded <- rbind(tcnSegsExpanded, segRowsT) verbose && exit(verbose) next } # if (isSplitter) nbrOfTCNLociKK <- tcnSegments[kk,"tcnNbrOfLoci"] verbose && cat(verbose, "Number of TCN loci in segment: ", nbrOfTCNLociKK) # Sanity check .stop_if_not(!isEmptySegment || (isEmptySegment && (nbrOfTCNLociKK == 0))) if (nbrOfTCNLociKK > 0) { # Extract locus data for TCN segment rows <- rowStart:rowEnd ## if (nrow(knownSegments) == 0) { ## gammaT <- tcnSegments[kk,"tcnMean"] ## verbose && print(verbose, all.equal(mean(dataKK$CT, na.rm=TRUE), gammaT, tolerance=tol)) ## .stop_if_not(all.equal(mean(dataKK$CT, na.rm=TRUE), gammaT, tolerance=tol)) ## } } else { rows <- integer(0) } # if (nbrOfTCNLociKK > 0) dataKK <- data[rows,,drop=FALSE] nbrOfLociKK <- nrow(dataKK) # Sanity check .stop_if_not(length(dataKK$CT) == nbrOfTCNLociKK) ## .stop_if_not(sum(!is.na(dataKK$CT)) == nbrOfTCNLociKK) verbose && cat(verbose, "Locus data for TCN segment:") verbose && str(verbose, dataKK) verbose && cat(verbose, "Number of loci: ", nbrOfLociKK) hasDH <- !is.null(dataKK$rho) if (hasDH) { isSnpKK <- !is.na(dataKK$rho) isHetsKK <- (isSnpKK & (dataKK$rho > 0)) } else { isSnpKK <- !is.na(dataKK$muN) isHetsKK <- (isSnpKK & (dataKK$muN == 1/2)) } nbrOfSnpsKK <- sum(isSnpKK) nbrOfHetsKK <- sum(isHetsKK) verbose && printf(verbose, "Number of SNPs: %d (%.2f%%)\n", nbrOfSnpsKK, 100*nbrOfSnpsKK/nbrOfLociKK) verbose && printf(verbose, "Number of heterozygous SNPs: %d (%.2f%%)\n", nbrOfHetsKK, 100*nbrOfHetsKK/nbrOfSnpsKK) # Since segments in 'knownSegments' has already been used in the TCN # segmentation, they are not needed in the DH segmentation. currChromosome <- data$chromosome[1] verbose && cat(verbose, "Chromosome: ", currChromosome) knownSegmentsT <- data.frame(chromosome=currChromosome, start=xStart, end=xEnd) verbose && enter(verbose, "Segmenting DH signals") fields <- attachLocally(dataKK, fields=c("chromosome", "x", "rho", "index")) fit <- segmentByCBS(rho, chromosome=chromosome, x=x, joinSegments=joinSegments, knownSegments=knownSegmentsT, alpha=alphaDH, undo=undoDH, ..., seed=seeds[["DH"]], verbose=verbose) verbose && str(verbose, fit) dhSegments <- fit$output dhSegRowsKK <- fit$segRows verbose && cat(verbose, "DH segmentation (locally-indexed) rows:") verbose && print(verbose, dhSegRowsKK) verbose && str(verbose, index) # Remap to genome-wide indices for (cc in 1:2) { dhSegRowsKK[,cc] <- index[dhSegRowsKK[,cc]] } verbose && cat(verbose, "DH segmentation rows:") verbose && print(verbose, dhSegRowsKK) # Not needed anymore rm(list=fields) fit <- NULL verbose && exit(verbose) # Drop dummy columns keep <- setdiff(colnames(dhSegments), c("sampleName", "chromosome")) dhSegments <- dhSegments[,keep,drop=FALSE] # Tag fields by DH names <- names(dhSegments) # Adding 'dh' prefix to column names names <- sprintf("dh%s", capitalize(names)) names(dhSegments) <- names # Special case: If there where not enough data to segment DH... if (nrow(dhSegments) == 0) { dhSegments <- dhSegments[NA_integer_,,drop=FALSE] dhSegRowsKK <- dhSegRowsKK[NA_integer_,,drop=FALSE] } verbose && cat(verbose, "DH segmentation table:") verbose && print(verbose, dhSegments) verbose && print(verbose, dhSegRowsKK) # Expand the TCN segmentation result data frame rows <- rep(kk, times=nrow(dhSegments)) verbose && cat(verbose, "Rows:") verbose && print(verbose, rows) tcnSegmentsKK <- tcnSegments[rows,,drop=FALSE] tcnSegRowsKK <- tcnSegRows[rows,,drop=FALSE] # Sanity check .stop_if_not(nrow(tcnSegmentsKK) == nrow(dhSegments)) .stop_if_not(nrow(tcnSegRowsKK) == nrow(dhSegments)) .stop_if_not(all(is.na(tcnSegRowsKK[,1]) | is.na(dhSegRowsKK[,1]) | (tcnSegRowsKK[,1] <= dhSegRowsKK[,1]))) .stop_if_not(all(is.na(tcnSegRowsKK[,2]) | is.na(dhSegRowsKK[,2]) | (dhSegRowsKK[,2] <= tcnSegRowsKK[,2]))) verbose && cat(verbose, "TCN segmentation rows:") verbose && print(verbose, tcnSegRowsKK) .stop_if_not(all(tcnSegRowsKK[,1] == tcnSegRowsKK[1,1], na.rm=TRUE)) .stop_if_not(all(tcnSegRowsKK[,2] == tcnSegRowsKK[1,2], na.rm=TRUE)) verbose && cat(verbose, "TCN and DH segmentation rows:") verbose && print(verbose, tcnSegRowsKK) verbose && print(verbose, dhSegRowsKK) verbose && print(verbose, tcnSegsExpanded) # Append tcnSegsExpanded <- rbind(tcnSegsExpanded, tcnSegRowsKK) verbose && cat(verbose, "TCN segmentation (expanded) rows:") verbose && print(verbose, tcnSegsExpanded) rownames(tcnSegsExpanded) <- NULL dhSegRows <- rbind(dhSegRows, dhSegRowsKK) rownames(dhSegRows) <- NULL verbose && cat(verbose, "TCN and DH segmentation rows:") verbose && print(verbose, tcnSegRows) verbose && print(verbose, dhSegRows) verbose && print(verbose, tcnSegsExpanded) # Sanity checks .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRows[,1] <= dhSegRows[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRows[-nrow(dhSegRows),2] < dhSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(tcnSegsExpanded[,1] <= tcnSegsExpanded[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegsExpanded[,1] <= dhSegRows[,1], na.rm=TRUE)) .stop_if_not(all(tcnSegsExpanded[,2] >= dhSegRows[,2], na.rm=TRUE)) ## if (!all(tcnSegsExpanded[-nrow(tcnSegsExpanded),2] < tcnSegsExpanded[-1,1], na.rm=TRUE)) { ## .stop_if_not(all(tcnSegsExpanded[-nrow(tcnSegsExpanded),2] < tcnSegsExpanded[-1,1], na.rm=TRUE)) ## } # Sanity check .stop_if_not(nrow(dhSegRows) == nrow(tcnSegsExpanded)) # Append information on number of SNPs and hets in CN region tcnSegmentsKK <- cbind( tcnSegmentsKK, tcnNbrOfSNPs=nbrOfSnpsKK, tcnNbrOfHets=nbrOfHetsKK ) verbose && cat(verbose, "Total CN segmentation table (expanded):") verbose && print(verbose, tcnSegmentsKK) # Sanity check .stop_if_not(nrow(tcnSegmentsKK) == nrow(dhSegments)) # Combine TCN and DH segmentation results tcndhSegments <- cbind( tcnId=rep(kk, times=nrow(dhSegments)), dhId=seq_len(nrow(dhSegments)), tcnSegmentsKK, dhSegments ) segs[[kk]] <- tcndhSegments verbose && cat(verbose, "(TCN,DH) segmentation for one total CN segment:") verbose && print(verbose, segs[[kk]]) verbose && exit(verbose) } # for (kk ...) segs <- Reduce(rbind, segs) rownames(segs) <- NULL } # if (flavor == "tcn") # Sanity check .stop_if_not(nrow(dhSegRows) == nrow(tcnSegsExpanded)) rownames(tcnSegRows) <- rownames(dhSegRows) <- NULL .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) if (flavor != "tcn") { .stop_if_not(all(dhSegRows[,1] <= dhSegRows[,2], na.rm=TRUE)) } .stop_if_not(all(dhSegRows[-nrow(dhSegRows),2] < dhSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(tcnSegsExpanded[,1] <= tcnSegsExpanded[,2], na.rm=TRUE)) ## .stop_if_not(all(tcnSegsExpanded[-nrow(tcnSegsExpanded),2] < tcnSegsExpanded[-1,1], na.rm=TRUE)) # Move 'chromosome' column to the first column idx <- match("chromosome", names(segs)) idxs <- c(idx, seq_len(ncol(segs))[-idx]) segs <- segs[,idxs,drop=FALSE] verbose && print(verbose, segs) verbose && enter(verbose, "Calculating (C1,C2) per segment") # Append (C1,C2) estimates tcn <- segs$tcnMean dh <- segs$dhMean C1 <- 1/2*(1-dh)*tcn C2 <- tcn - C1 segs <- cbind(segs, c1Mean=C1, c2Mean=C2) verbose && exit(verbose) nbrOfSegs <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegs) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Create result object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - params <- list( alphaTCN = alphaTCN, alphaDH = alphaDH, flavor = flavor, tbn = tbn, joinSegments = joinSegments, knownSegments = knownSegments, seed = seed ) # Should we drop attributes? /HB 2010-09-24 .stop_if_not(all(data$index == seq_len(nrow(data)))) data$index <- NULL # Drop, because it is guaranteed to be ordered class(data) <- c("PairedPSCNData", class(data)) class(segs) <- c("PairedPSCNSegments", class(segs)) fit <- list( data = data, output = segs, tcnSegRows = tcnSegsExpanded, dhSegRows = dhSegRows, params = params ) class(fit) <- c("PairedPSCBS", "PSCBS", "AbstractCBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (avgTCN != "mean" || avgDH != "mean") { verbose && enter(verbose, "Updating mean level using different estimator") verbose && cat(verbose, "TCN estimator: ", avgTCN) verbose && cat(verbose, "DH estimator: ", avgDH) fit <- updateMeans(fit, avgTCN=avgTCN, avgDH=avgDH, verbose=less(verbose, 20)) verbose && exit(verbose) } if (is.element(flavor, c("tcn&dh", "sqrt(tcn)&dh"))) { fit$params$flavor <- gsub("&", ",", flavor, fixed=TRUE) # AD HOC. fit <- postsegmentTCN(fit, verbose=verbose) # Sanity check CT <- fit$data$CT tcnSegRows <- fit$tcnSegRows dhSegRows <- fit$dhSegRows for (jj in 1:nrow(tcnSegRows)) { tcnSegRowJJ <- unlist(tcnSegRows[jj,,drop=TRUE], use.names=FALSE) dhSegRowJJ <- unlist(dhSegRows[jj,,drop=TRUE], use.names=FALSE) .stop_if_not( is.na(tcnSegRowJJ[1]) || is.na(dhSegRowJJ[1]) || # A TCN segment must start at or before a DH segment... (tcnSegRowJJ[1] <= dhSegRowJJ[1]) || # ...unless there was an outlier at the left edge. (is.na(CT[dhSegRowJJ[1]]) && (tcnSegRowJJ[1] - 1L <= dhSegRowJJ[1])) ) .stop_if_not( is.na(tcnSegRowJJ[2]) || is.na(dhSegRowJJ[2]) || # A TCN segment must end at or after a DH segment... (dhSegRowJJ[2] <= tcnSegRowJJ[2]) || # ...unless there was an outlier at the right edge. (is.na(CT[dhSegRowJJ[2]]) && (dhSegRowJJ[2] <= tcnSegRowJJ[2] + 1L)) ) } # for (jj ...) # Not needed anymore CT <- tcnSegRows <- dhSegRows <- NULL } verbose && print(verbose, head(as.data.frame(fit))) verbose && print(verbose, tail(as.data.frame(fit))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit }) # segmentByPairedPSCBS() setMethodS3("segmentByPairedPSCBS", "data.frame", function(CT, ...) { # To please R CMD check data <- CT segmentByPairedPSCBS(CT=data$CT, thetaT=data$thetaT, thetaN=data$thetaN, betaT=data$betaT, betaN=data$betaN, muN=data$muN, rho=data$rho, chromosome=data$chromosome, x=data$x, ...) }) setMethodS3("segmentByPairedPSCBS", "PairedPSCBS", function(...) { resegment(...) }) # segmentByPairedPSCBS() PSCBS/R/PairedPSCBS.callLOH.R0000644000176200001440000002422014564051545014735 0ustar liggesusers##########################################################################/** # @set class=PairedPSCBS # @RdocMethod callLOH # # @title "Calls segments that are in LOH" # # \description{ # @get "title", i.e. that have "zero" minor copy number. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # call to use.} # \item{...}{Additional arguments passed to the caller.} # \item{minSize}{An optional @integer specifying the minimum number # of data points in order to call a segments. If fewer data points, # then the call is set to @NA regardless.} # \item{xorCalls}{If @TRUE, a region already called AB, will # for consistency never be called LOH, resulting in either an LOH # call set to @FALSE or @NA (as explained below).} # \item{force}{If @FALSE, and allelic-balance calls already exits, # then nothing is done, otherwise the calls are done.} # } # # \value{ # Returns a @see "PairedPSCBS" object with LOH calls. # } # # \section{AB and LOH consistency}{ # Biologically, a segment can not be both in allelic balance (AB) and # in loss-of-heterozygosity (LOH) at the same time. # To avoid reporting such inconsistencies, the LOH caller will, # if argument \code{xorCalls=TRUE}, never report a segment to be in # LOH if it is already called to be in AB. # However, regardless of of the AB call, a segment is still always # tested for LOH, to check weather the LOH caller is consistent with the # AB caller or not. Thus, in order to distinguish the case where # the AB caller and LOH caller agree from when they disagree, # we report either (AB,LOH)=(TRUE,FALSE) or (TRUE,NA). The former is # reported when they are consistent, and the latter when they are not, # or when the LOH caller could not call it. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "callLowC1ByC1", # @seemethod "callExtremeAllelicImbalanceByDH". # } # #*/########################################################################### setMethodS3("callLOH", "PairedPSCBS", function(fit, flavor=c("SmallC1", "LargeDH"), ..., minSize=1, xorCalls=TRUE, force=FALSE) { # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'minSize': minSize <- Arguments$getDouble(minSize, range=c(1,Inf)) # Argument 'xorCalls': xorCalls <- Arguments$getLogical(xorCalls) # Already done? segs <- as.data.frame(fit) calls <- segs$lohCall if (!force && !is.null(calls)) { return(invisible(fit)) } if (flavor == "SmallC1") { fit <- callLowC1ByC1(fit, ..., callName="loh") } else if (flavor == "LargeDH") { fit <- callExtremeAllelicImbalanceByDH(fit, ..., callName="loh") } else { stop("Cannot call LOH. Unsupported flavor: ", flavor) } # Don't call segments with too few data points? if (minSize > 1) { segs <- as.data.frame(fit) ns <- segs$dhNbrOfLoci calls <- segs$lohCall calls[ns < minSize] <- NA segs$lohCall <- calls fit$output <- segs # Not needed anymore segs <- calls <- NULL } # Don't call a segment LOH if it already called AB? if (xorCalls) { segs <- as.data.frame(fit) if (is.element("abCall", names(segs))) { calls <- segs$lohCall otherCalls <- segs$abCall # If called (TRUE) and already called (TRUE) # by the other caller, call it as NA. calls[calls & otherCalls] <- NA segs$lohCall <- calls fit$output <- segs } } return(invisible(fit)) }) setMethodS3("callLowC1ByC1", "PairedPSCBS", function(fit, delta=estimateDeltaLOH(fit, flavor="minC1|nonAB"), alpha=0.05, ..., callName="lowc1", verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'delta': if (delta != -Inf) { delta <- Arguments$getDouble(delta, range=c(0,Inf)) } # Argument 'alpha': alpha <- Arguments$getDouble(alpha, range=c(0,1)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments of allelic balance from one-sided DH bootstrap confidence intervals") verbose && cat(verbose, "delta (offset adjusting for bias in C1): ", delta) verbose && cat(verbose, "alpha (CI quantile; significance level): ", alpha) # Calculate C1 confidence intervals, if not already done probs <- c(alpha, 1-alpha) fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) segs <- as.data.frame(fit) # Extract confidence interval alphaTag <- sprintf("%g%%", 100*alpha) column <- sprintf("c1_%s", alphaTag) # Sanity checks .stop_if_not(is.element(column, colnames(segs))) # One-sided test verbose && enter(verbose, "Calling segments") value <- segs[,column, drop=TRUE] call <- (value < delta) nbrOfCalls <- sum(call, na.rm=TRUE) verbose && printf(verbose, "Number of segments called low C1 (LowC1, \"LOH_C1\"): %d (%.2f%%) of %d\n", nbrOfCalls, 100*nbrOfCalls/nrow(segs), nrow(segs)) verbose && exit(verbose) key <- sprintf("%sCall", callName) # calls <- data.frame(lowc1Call=call) # colnames(calls) <- key # segs <- cbind(segs, calls) segs[[key]] <- call fit$output <- segs # Append 'delta' and 'alpha' to parameters params <- fit$params params$deltaLowC1 <- delta params$alphaLowC1 <- alpha fit$params <- params verbose && exit(verbose) fit }, private=TRUE) # callLowC1ByC1() setMethodS3("callExtremeAllelicImbalanceByDH", "PairedPSCBS", function(fit, delta=0.60, alpha=0.05, ..., callName="aiHigh", verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'delta': delta <- Arguments$getDouble(delta, range=c(0,Inf)) # Argument 'alpha': alpha <- Arguments$getDouble(alpha, range=c(0,1)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments of extreme allelic imbalance (AI) from one-sided DH bootstrap confidence intervals") verbose && cat(verbose, "delta (offset adjusting for normal contamination and other biases): ", delta) verbose && cat(verbose, "alpha (CI quantile; significance level): ", alpha) # Calculate DH confidence intervalls, if not already done probs <- c(alpha, 1-alpha) fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) segs <- as.data.frame(fit) # Extract confidence interval alphaTag <- sprintf("%g%%", 100*alpha) column <- sprintf("dh_%s", alphaTag) # Sanity checks .stop_if_not(is.element(column, colnames(segs))) # One-sided test verbose && enter(verbose, "Calling segments") value <- segs[,column, drop=TRUE] call <- (value >= delta) nbrOfCalls <- sum(call, na.rm=TRUE) verbose && printf(verbose, "Number of segments called high allelic imbalance (AI/\"LOH_AI\"): %d (%.2f%%) of %d\n", nbrOfCalls, 100*nbrOfCalls/nrow(segs), nrow(segs)) verbose && exit(verbose) key <- sprintf("%sCall", callName) # calls <- data.frame(aiHighCall=call) # colnames(calls) <- key # segs <- cbind(segs, calls) segs[[key]] <- call fit$output <- segs # Append 'delta' and 'alpha' to parameters params <- fit$params params$deltaExtremeDH <- delta params$alphaExtremeDH <- alpha fit$params <- params verbose && exit(verbose) fit }, private=TRUE) # callExtremeAllelicImbalanceByDH() ############################################################################## # HISTORY # 2012-05-30 # o BUG FIX: callLOH(..., force=TRUE) would append multiple 'lohCall' # columns, if called multiple times. # o BUG FIX: callLowC1ByC1() and callExtremeAllelicImbalanceByDH() would # append multiple call columns with the same name if called multiple times. # 2012-01-15 # o DOCUMENTATION: Added details to the help of callLOH() and callAB() on # the difference between (AB,LOH)=(TRUE,FALSE) and (AB,LOH)=(TRUE,NA). # 2011-06-14 # o Updated code to recognize new column names. # 2011-05-29 # o Renamed all arguments, variables, function named 'tau' to 'delta'. # 2011-04-14 # o BUG FIX: Argument 'minSize' of callAB() and callLOH() had no effect. # 2011-04-12 # o Added argument 'minSize' to callLOH() for PairedPSCBS. # o Added argument 'xorCalls' to callLOH() for PairedPSCBS. # 2011-04-11 # o Added argument 'callName' to callExtremeAllelicImbalanceByDH() and # callLowC1ByC1(). # 2011-04-10 # o Added callLOH(). # 2010-12-07 # o Added callLowC1ByC1() and callABandLowC1(). # 2010-11-27 # o Corrected verbose output to call results. # 2010-11-26 [HB] # o Now all call functions estimate symmetric bootstrap quantiles for # convenince of plotting confidence intervals. # o BUG FIX: callABandHighAI() for PairedPSCBS used the old DH-only # bootstrap method. # o BUG FIX: The call functions, for instance callABandHighAI(), would throw # 'Error in quantile.default(x, probs = alpha) : missing values and NaN's # not allowed if 'na.rm' is FALSE' unless bootstrapTCNandDHByRegion() was # run before. # 2010-11-22 [HB] # o Added more verbose output to callABandHighAI(). # o Updated callAllelicBalanceByDH() and callExtremeAllelicImbalanceByDH() # to utilize bootstrapTCNandDHByRegion(). # 2010-10-25 [HB] # o Relaced argument 'ciRange' with 'alpha' for callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH(). # o Renamed callAllelicBalance() to callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH() to callExtremeAllelicImbalance(). # o Added arguments 'alphaAB' and 'alphaHighAI' to callABandHighAI(). # o Added sanity checks to the call methods. # o Now arguments '...' to callABandHighAI() are passed down. # o Now also arguments '...' to callAllelicBalance() and # callExtremeAllelicImbalance() are passed to bootstrapDHByRegion(). # o Added argument 'ciRange' to callAllelicBalance() and # callExtremeAllelicImbalance(). # 2010-09-16 [HB] # o Added callABandHighAI(). # o Added callAllelicBalance() and callExtremeAllelicImbalance(). # o Created. ############################################################################## PSCBS/R/999.package.R0000644000176200001440000000351615000272550013375 0ustar liggesusers#########################################################################/** # @RdocPackage "PSCBS" # @eval "rd <- gsub('\\alias{PSCBS}', '', rd, fixed=TRUE); ''" # # \description{ # @eval "packageDescription('PSCBS')$Description". # # This package should be considered to be in an alpha or beta phase. # You should expect the API to be changing over time. # } # # \section{Installation and updates}{ # To install this package, use \code{install.packages("PSCBS")}. # } # # \section{To get started}{ # To get started, see: # \enumerate{ # \item Vignettes '\href{../doc/index.html}{Parent-specific copy-number segmentation using Paired PSCBS}' and '\href{../doc/index.html}{Total copy-number segmentation using CBS}'. # \item @see "segmentByCBS" - segments total copy-numbers, or any # other unimodal genomic signals, using the CBS method [3,4]. # \item @see "segmentByPairedPSCBS" - segments allele-specific # tumor signal from a tumor \emph{with} a matched normal # using the Paired PSCBS method [1,2]. # \item @see "segmentByNonPairedPSCBS" - segments allele-specific # tumor signal from a tumor \emph{without} a matched normal # using the Non-Paired PSCBS method adopted from [1,2]. # } # } # # \section{How to cite}{ # Please use [1] and [2] to cite when using Paired PSCBS, # and [3] and [4] when using CBS. # When using Non-Paired PSCBS, please cite [1] and [2] as well. # } # # @author # # \section{License}{ # @eval "packageDescription('PSCBS')$License". # } # # \references{ # [1] @include "../incl/OlshenA_etal_2011.Rd" \cr # [2] @include "../incl/BengtssonH_etal_2010.Rd" \cr # [3] @include "../incl/OlshenVenkatraman_2004.Rd" \cr # [4] @include "../incl/VenkatramanOlshen_2007.Rd" \cr # } #*/######################################################################### PSCBS/R/gapsToSegments.R0000644000176200001440000001050014564051545014420 0ustar liggesusers###########################################################################/** # @set "class=data.frame" # @RdocMethod gapsToSegments # @alias gapsToSegments # # @title "Gets the genomic segments that are complementary to the gaps" # # \description{ # @get "title", with default chromosome boundaries being \code{-Inf} # and \code{+Inf}. # } # # @synopsis # # \arguments{ # \item{gaps}{A @data.frame with columns \code{chromosome}, \code{start}, # and \code{stop}. Any overlapping gaps will throw an error.} # \item{resolution}{A non-negative @numeric specifying the minimum # length unit, which by default equals one nucleotide/base pair.} # \item{minLength}{Minimum length of segments to be kept.} # \item{dropGaps}{If @TRUE, the gaps themselves are not part of the output.} # \item{...}{Not used.} # } # # \value{ # Returns @data.frame of least one row with columns \code{chromosome} # if that argument is given), \code{start}, \code{stop} and \code{length}. # The segments are ordered along the genome. # } # # @author "HB" # # \seealso{ # @see "findLargeGaps". # } # # @keyword IO #*/########################################################################### setMethodS3("gapsToSegments", "data.frame", function(gaps, resolution=1L, minLength=0L, dropGaps=FALSE, ...) { # To please R CMD check chromosome <- NULL; rm(list="chromosome") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'gaps': keys <- colnames(gaps) .stop_if_not(all(is.element(c("start", "end"), keys))) .stop_if_not(all(gaps$start <= gaps$end, na.rm=TRUE)) hasChr <- is.element("chromosome", keys) ## Nothing more to do? if (nrow(gaps) == 0L) { knownSegments <- data.frame(chromosome=integer(1L), start=-Inf, end=+Inf) if (!hasChr) knownSegments$hromosome <- NULL return(knownSegments) } # Order gaps by the genome o <- order(gaps$chromosome, gaps$start, gaps$end) gaps <- gaps[o,] # For each chromosome... knownSegments <- NULL chromosomes <- sort(unique(gaps$chromosome)) for (chr in chromosomes) { gapsCC <- subset(gaps, chromosome == chr) nCC <- nrow(gapsCC) starts <- gapsCC$start ends <- gapsCC$end # Assert that no overlapping gaps where specified if (!all(starts[-1] >= ends[-nCC], na.rm=TRUE)) { print(knownSegments) stop("INTERNAL ERROR: Detected overlapping gaps on chromosome ", chr, " in argument 'gaps'.") } # All boundaries in order # (this is possible because gaps are non-overlapping) naValue <- NA_real_ if (dropGaps) { bps <- rep(naValue, times=2*nCC) bps[seq(from=1, to=2*nCC, by=2)] <- starts - resolution bps[seq(from=2, to=2*nCC, by=2)] <- ends + resolution bps <- c(-Inf, bps, +Inf) dim(bps) <- c(2L, nCC+1L) } else { bps <- rep(naValue, times=4*nCC) bps[seq(from=1, to=4*nCC, by=4)] <- starts - resolution bps[seq(from=2, to=4*nCC, by=4)] <- starts bps[seq(from=3, to=4*nCC, by=4)] <- ends bps[seq(from=4, to=4*nCC, by=4)] <- ends + resolution bps <- c(-Inf, bps, +Inf) dim(bps) <- c(2L, 2*nCC+1L) } knownSegmentsCC <- data.frame(chromosome=chr, start=bps[1L,], end=bps[2L,]) knownSegments <- rbind(knownSegments, knownSegmentsCC) } # for (chr ...) # o <- with(knownSegments, order(chromosome, start, end)) # knownSegments <- knownSegments[o,] # rownames(knownSegments) <- NULL # Append segment lengths knownSegments$length <- knownSegments$end - knownSegments$start # Drop too short segments keep <- (knownSegments$length >= minLength) knownSegments <- knownSegments[keep,] # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate generated 'knownSegments' # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - .stop_if_not(is.data.frame(knownSegments)) .stop_if_not(nrow(knownSegments) >= 1L) for (chr in sort(unique(knownSegments$chromosome))) { dd <- subset(knownSegments, chromosome == chr) # Known segments must not overlap if (!all(dd$start[-1] >= dd$end[-nrow(dd)], na.rm=TRUE)) { stop("INTERNAL ERROR: Detected overlapping segments on chromosome ", chr, " in generated 'knownSegments'.") } } knownSegments }) # gapsToSegments() PSCBS/R/PairedPSCBS.extractSegmentDataByLocus.R0000644000176200001440000000552714564051545020560 0ustar liggesuserssetMethodS3("extractSegmentDataByLocus", "PairedPSCBS", function(fit, fields=NULL, ..., verbose=FALSE) { # Extract data segs <- getSegments(fit, splitters=TRUE) data <- getLocusData(fit, ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fields': if (!is.null(fields)) { fields <- Arguments$getCharacters(fields) unknown <- fields[!is.element(fields, colnames(segs))] if (length(unknown) > 0L) { stop("Unknown segment fields: ", paste(sQuote(unknown), collapse=", ")) } } else { fields <- colnames(segs) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Extracting segment data by locus") # Extract segment fields chromosome <- data$chromosome x <- data$x y <- data[,3L] segs <- segs[,fields] nbrOfLoci <- nrow(data) verbose && printf(verbose, "Segment fields: [%d] %s\n", length(fields), paste(sQuote(fields), collapse=", ")) verbose && cat(verbose, "Number of loci: ", nbrOfLoci) # Allocate segment fields at the locus level dataL <- matrix(NA, nrow=nbrOfLoci, ncol=length(fields)) colnames(dataL) <- fields dataL <- as.data.frame(dataL) verbose && cat(verbose, "Allocated results:") verbose && str(verbose, dataL) verbose && enter(verbose, "Extracting segment by segment") # For each segment... for (ss in seq_len(nrow(segs))) { verbose && enter(verbose, sprintf("Segment %d of %d", ss, nrow(segs))) seg <- segs[ss,] idxs <- which(chromosome == seg$chromosome & seg$tcnStart <= x & x <= seg$tcnEnd) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) verbose && cat(verbose, "Number of loci in segment: ", length(idxs)) # Sanity check ## .stop_if_not(length(idxs) == seg$tcnNbrOfLoci) segsSS <- seg[fields] verbose && cat(verbose, "Segment data extracted:") verbose && print(verbose, segsSS) for (field in fields) { dataL[idxs,field] <- segsSS[[field]] } verbose && exit(verbose) } # for (ss ...) verbose && exit(verbose) # The calls for loci that have missing annotations or observations, # should also be missing, i.e. NA. nok <- (is.na(chromosome) | is.na(x) | is.na(y)) dataL[nok,] <- NA # Sanity check .stop_if_not(nrow(dataL) == nbrOfLoci) .stop_if_not(ncol(dataL) == length(fields)) verbose && exit(verbose) dataL }, protected=TRUE) # extractSegmentDataByLocus() ############################################################################## # HISTORY # 2013-10-27 # o Added extractSegmentDataByLocus() for PairedPSCBS adopted from # extractCallsByLocus() of 'PSCBS'. ############################################################################## PSCBS/R/AbstractCBS.R0000644000176200001440000004413614564202700013553 0ustar liggesusers###########################################################################/** # @RdocClass AbstractCBS # # @title "The AbstractCBS class" # # \description{ # @classhierarchy # # All CBS-style segmentation results extend this class, e.g. # @see "CBS" and @see "PairedPSCBS". # } # # @synopsis # # \arguments{ # \item{fit}{A @list structure containing the segmentation results.} # \item{sampleName}{A @character string.} # \item{...}{Not used.} # } # # \section{Fields and Methods}{ # @allmethods "public" # } # # @author "HB" # # @keyword internal #*/########################################################################### setConstructorS3("AbstractCBS", function(fit=list(), sampleName=fit$sampleName, ...) { # Argument 'sampleName': if (!is.null(sampleName)) { sampleName <- Arguments$getCharacter(sampleName) } fit$sampleName <- sampleName extend(fit, "AbstractCBS") }) setMethodS3("print", "AbstractCBS", function(x, ...) { # To please R CMD check fit <- x segs <- getSegments(fit, simplify=TRUE, ...) print(segs) }, protected=TRUE) setMethodS3("all.equal", "AbstractCBS", function(target, current, check.attributes=FALSE, ...) { # NOTE: Here we cannot trust argument '...', because it may contain # copies of 'target' and 'current' args <- list(...) drop <- integer(0L) for (kk in seq_along(args)) { if (identical(args[[kk]], target)) drop <- c(drop, kk) if (identical(args[[kk]], current)) drop <- c(drop, kk) } if (length(drop) > 0L) { args <- args[-drop] str(args) # assign("...", args, inherits=FALSE) } args <- list(...) # Compare class attributes res <- all.equal(class(target), class(current)) if (!isTRUE(res)) { return(res) } # Compare locus-level data dataT <- getLocusData(target) dataC <- getLocusData(current) res <- all.equal(dataT, dataC, check.attributes=check.attributes) if (!isTRUE(res)) { attr(res, "what") <- "getLocusData()" return(res) } # Compare segments dataT <- getSegments(target) dataC <- getSegments(current) res <- all.equal(dataT, dataC, check.attributes=check.attributes) if (!isTRUE(res)) { attr(res, "what") <- "getSegments()" return(res) } # Compare field names fieldsT <- names(target) fieldsC <- names(current) res <- all.equal(fieldsT, fieldsC, check.attributes=check.attributes) if (!isTRUE(res)) { attr(res, "what") <- "names" return(res) } # Compare other fields for (key in fieldsT) { dataT <- target[[key]] dataC <- current[[key]] res <- all.equal(dataT, dataC, check.attributes=check.attributes) if (!isTRUE(res)) { attr(res, "what") <- sprintf("[[\"%s\"]]", key) return(res) } } # for (key ...) return(TRUE) }, protected=TRUE) ###########################################################################/** # @RdocMethod getSampleName # @aliasmethod sampleName # # @title "Gets the name of the sample segmented" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a @character string. # } # # @author # # \seealso{ # @seemethod "setSampleName". # @seeclass. # } #*/########################################################################### setMethodS3("getSampleName", "AbstractCBS", function(fit, ...) { name <- fit$sampleName if (is.null(name)) { name <- NA_character_ } name }, protected=TRUE) setMethodS3("sampleName", "AbstractCBS", function(fit, ...) { getSampleName(fit) }, protected=TRUE) ###########################################################################/** # @RdocMethod setSampleName # @aliasmethod sampleName<- # # @title "Sets the name of the sample segmented" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{name}{A @character string.} # \item{...}{Not used.} # } # # \value{ # Returns (invisibly) an updated object. # } # # @author # # \seealso{ # @seeclass. # } # # @keyword internal #*/########################################################################### setMethodS3("setSampleName", "AbstractCBS", function(fit, name, ...) { # Argument 'value': name <- Arguments$getCharacter(name) fit$sampleName <- name invisible(fit) }, protected=TRUE) setMethodS3("sampleName<-", "AbstractCBS", function(x, value) { setSampleName(x, value) }, protected=TRUE, addVarArgs=FALSE) "sampleName<-" <- function(x, value) { UseMethod("sampleName<-") } ###########################################################################/** # @RdocMethod getLocusData # @aliasmethod setLocusData # @alias setLocusData.AbstractCBS # # @title "Gets the locus-level data" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a JxL @data.frame, where J in the number of loci, # and L is the number of locus-specific fields. # } # # @author # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("getLocusData", "AbstractCBS", abstract=TRUE) setMethodS3("setLocusData", "AbstractCBS", function(fit, loci, ...) { # Argument 'loci': loci <- Arguments$getInstanceOf(loci, "data.frame") nbrOfLoci <- nbrOfLoci(fit) if (nrow(loci) != nbrOfLoci) { stop("Cannot set locus-level data. The number of loci to be set differ from the existing number of loci: ", nrow(loci), " != ", nbrOfLoci) } fit$data <- loci invisible(fit) }, protected=TRUE) setMethodS3("getLocusSignalNames", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("getSegmentTrackPrefixes", "AbstractCBS", abstract=TRUE, protected=TRUE) ###########################################################################/** # @RdocMethod nbrOfLoci # # @title "Gets the number of loci" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{splitters, ...}{Arguments passed to @seemethod "getLocusData".} # } # # \value{ # Returns an @integer. # } # # @author # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("nbrOfLoci", "AbstractCBS", function(fit, splitters=FALSE, ...) { data <- getLocusData(fit, splitters=splitters, ...) nrow(data) }) ###########################################################################/** # @RdocMethod getSegments # @aliasmethod setSegments # @alias setSegments.AbstractCBS # # @title "Gets the segments" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a SxK @data.frame, where S in the number of segments, # and K is the number of segment-specific fields. # } # # @author # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("getSegments", "AbstractCBS", abstract=TRUE) setMethodS3("setSegments", "AbstractCBS", function(fit, segments, splitters=TRUE, ...) { # Argument 'segments': segments <- Arguments$getInstanceOf(segments, "data.frame") nbrOfSegs <- nbrOfSegments(fit, splitters=splitters, ...) if (nrow(segments) != nbrOfSegs) { stop("Cannot set segments. The number of segments to be set differ from the existing number of segments: ", nrow(segments), " != ", nbrOfSegs) } fit$output <- segments invisible(fit) }, protected=TRUE) setMethodS3("getChangePoints", "AbstractCBS", abstract=TRUE) ###########################################################################/** # @RdocMethod resetSegments # # @title "Reset the segments" # # \description{ # @get "title". More precisely, it removes columns in the segmentation # result table that have been added by methods after the actual # segmentation method, e.g. bootstrap estimated mean level quantiles # and various calls. # It leave the basic segmentation results untouched, # i.e. the partitioning and the segment means. # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns an object if the same class as the input result. # } # # @author # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("resetSegments", "AbstractCBS", function(fit, ...) { segs <- getSegments(fit, splitters=TRUE) names <- colnames(segs) excl <- NULL # Drop all quantile mean level estimates (from bootstrapping) idxs <- grep("_[0-9.]*[%]$", names) excl <- c(excl, idxs) # Drop all calls idxs <- grep("Call$", names) excl <- c(excl, idxs) excl <- unique(excl) if (length(excl) > 0L) { segs <- segs[,-excl] } fit <- setSegments(fit, segs, splitters=TRUE) invisible(fit) }, protected=TRUE) ###########################################################################/** # @RdocMethod nbrOfSegments # # @title "Gets the number of segments" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{splitters, ...}{Arguments passed to @seemethod "getSegments".} # } # # \value{ # Returns an @integer. # } # # @author # # \seealso{ # @seemethod "nbrOfChangePoints" # @seemethod "nbrOfChromosomes" # @seeclass # } #*/########################################################################### setMethodS3("nbrOfSegments", "AbstractCBS", function(this, splitters=FALSE, ...) { nrow(getSegments(this, splitters=splitters, ...)) }) ###########################################################################/** # @RdocMethod nbrOfChangePoints # # @title "Gets the number of change points" # # \description{ # @get "title", which is defined as the number of segments minus # the number of chromosomes. # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns an @integer. # } # # @author # # \seealso{ # @seemethod "nbrOfSegments" # @seemethod "nbrOfChromosomes" # @seeclass # } #*/########################################################################### setMethodS3("nbrOfChangePoints", "AbstractCBS", function(fit, ignoreGaps=FALSE, dropEmptySegments=TRUE, ...) { segs <- getSegments(fit, splitters=TRUE, addGaps=!ignoreGaps) if (dropEmptySegments) { prefix <- getSegmentTrackPrefixes(fit) keys <- sapply(prefix, FUN=function(x) { toCamelCase(paste(c(x, "nbr of loci"), collapse=" ")) }) counts <- as.matrix(segs[,keys]) counts <- rowSums(counts, na.rm=TRUE) segs$chromosome[counts == 0L] <- NA } sum(!is.na(diff(segs$chromosome))) }) ###########################################################################/** # @RdocMethod as.data.frame # # @title "Gets the table of segments" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a @data.frame, where each row corresponds to # a unique segment. # } # # @author # # \seealso{ # Utilizes @seemethod "getSegments". # @seeclass. # } #*/########################################################################### setMethodS3("as.data.frame", "AbstractCBS", function(x, ...) { getSegments(x, ...) }, protected=TRUE) ###########################################################################/** # @RdocMethod getChromosomes # # @title "Gets the set of chromosomes" # # \description{ # @get "title" in the segmentation result. # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to @seemethod "getSegments".} # } # # \value{ # Returns a unique and sorted @vector of chromosomes segmented. # } # # @author # # \seealso{ # @seemethod "nbrOfChromosomes". # @seeclass # } #*/########################################################################### setMethodS3("getChromosomes", "AbstractCBS", function(this, ...) { segs <- getSegments(this, ...) chromosomes <- sort(unique(segs$chromosome), na.last=TRUE) # Drop NA dividers if (length(chromosomes) > 1) { chromosomes <- chromosomes[!is.na(chromosomes)] } chromosomes }) ###########################################################################/** # @RdocMethod nbrOfChromosomes # # @title "Gets the number of chromosomes" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to @seemethod "getChromosomes".} # } # # \value{ # Returns an @integer. # } # # @author # # \seealso{ # @seemethod "getChromosomes". # @seeclass # } #*/########################################################################### setMethodS3("nbrOfChromosomes", "AbstractCBS", function(this, ...) { length(getChromosomes(this, ...)) }) setMethodS3("getSegmentSizes", "AbstractCBS", function(fit, by=c("length", "count"), ...) { by <- match.arg(by) if (by == "length") { prefix <- getSegmentTrackPrefixes(fit)[1] keys <- toCamelCase(paste(prefix, " ", c("start", "end"))) } else if (by == "count") { keys <- "nbrOfLoci" } data <- getSegments(fit, ...)[,keys] if (by == "length") { res <- data[[2L]]-data[[1L]]+1L } else if (by == "count") { res <- data[[1L]] } res }) setMethodS3("extractCNs", "AbstractCBS", abstract=TRUE) setMethodS3("sampleCNs", "AbstractCBS", function(fit, size=NULL, ...) { data <- extractCNs(fit, ...) if (!is.null(size)) { sizes <- getSegmentSizes(fit, ...) # Sanity check .stop_if_not(length(sizes) == nrow(data)) idxs <- sample(nrow(data), size=size, replace=TRUE, prob=sizes) data <- data[idxs,,drop=FALSE] } data }) ###########################################################################/** # @RdocMethod updateMeans # @alias updateMeans.CBS # @alias updateMeans.NonPairedPSCBS # @alias updateMeans.PairedPSCBS # # @title "Updates the CN mean levels for each segment independently" # # \description{ # @get "title" as if they were one large segment. # The locus-level data is not updated/modified. # } # # @synopsis # # \arguments{ # \item{...}{Arguments specific to the class.} # } # # \value{ # Returns an object of the same class. # } # # @author # # @keyword internal #*/########################################################################### setMethodS3("updateMeans", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("getMeanEstimators", "AbstractCBS", function(fit, which=NULL, default=mean, ...) { estList <- fit$params$meanEstimators if (is.null(estList)) { estList <- list() } if (is.null(which)) which <- names(estList) for (key in which) { fcn <- estList[[key]] if (is.null(fcn)) { fcn <- default } else if (is.character(fcn)) { fcn <- get(fcn, mode="function") } estList[[key]] <- fcn } estList }, protected=TRUE) setMethodS3("setMeanEstimators", "AbstractCBS", function(fit, ...) { estList <- fit$params$meanEstimators if (is.null(estList)) { estList <- list() } args <- list(...) # Nothing todo? if (length(args) == 0L) { return(invisible(fit)) } keys <- names(args) if (is.null(keys)) { stop("Estimators arguments must be named.") } for (key in keys) { fcn <- args[[key]] if (is.function(fcn)) { } else if (is.character(fcn)) { if (!exists(fcn, mode="function")) { stop(sprintf("No such '%s' estimator function: %s", key, fcn)) } } else { stop(sprintf("Estimator argument '%s' must be a function or character string: %s", key, mode(fcn))) } estList[[key]] <- fcn } fit$params$meanEstimators <- estList invisible(fit) }, protected=TRUE) setMethodS3("resegment", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("getChromosomeRanges", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("getChromosomeOffsets", "AbstractCBS", function(fit, resolution=1e6, ...) { # Argument 'resolution': if (!is.null(resolution)) { resolution <- Arguments$getDouble(resolution, range=c(1,Inf)) } data <- getChromosomeRanges(fit, ...) splits <- data[,"start"] + data[,"length"] if (!is.null(resolution)) { splits <- ceiling(splits / resolution) splits <- resolution * splits } offsets <- c(0L, cumsum(splits)) names(offsets) <- c(rownames(data), NA) offsets }, protected=TRUE) # getChromosomeOffsets() ###########################################################################/** # @RdocMethod ploidy # @aliasmethod ploidy<- # @aliasmethod setPloidy # @aliasmethod adjustPloidyScale # @alias adjustPloidyScale.PairedPSCBS # @alias adjustPloidyScale # @alias ploidy # @alias ploidy<- # @alias setPloidy # # @title "Gets and sets ploidy" # # \description{ # @get "title". # } # # \usage{ # \method{ploidy}{AbstractCBS}(fit, ...) # \method{ploidy}{AbstractCBS}(fit) <- value # } # # \arguments{ # \item{fit}{An @see "AbstractCBS" object.} # \item{value}{An @integer (in \eqn{1,2,\ldots}) specifying the genome ploidy .} # \item{...}{Not used.} # } # # \value{ # Returns (invisibly) an updated object. # } # # @author # # \seealso{ # @seeclass. # } # # @keyword internal #*/########################################################################### setMethodS3("ploidy", "AbstractCBS", function(fit, ...) { ploidy <- fit$params$ploidy if (is.null(ploidy)) ploidy <- 2L ploidy }) setMethodS3("ploidy<-", "AbstractCBS", function(fit, value) { fit <- setPloidy(fit, ploidy=value, update=TRUE) invisible(fit) }) "ploidy<-" <- function(fit, value) { UseMethod("ploidy<-") } setMethodS3("setPloidy", "AbstractCBS", function(fit, ploidy=2L, update=TRUE, ...) { # Argument 'ploidy': ploidy <- Arguments$getInteger(ploidy, range=c(1,Inf)) if (update) { # Calculate rescaling factor oldPloidy <- ploidy(fit) scale <- ploidy / oldPloidy # Nothing todo? if (scale != 1) { fit <- adjustPloidyScale(fit, scale=scale, ...) } } fit$params$ploidy <- ploidy invisible(fit) }, protected=TRUE) setMethodS3("adjustPloidyScale", "AbstractCBS", abstract=TRUE) ###########################################################################/** # @RdocMethod normalizeTotalCNs # @alias normalizeTotalCNs # @alias normalizeTotalCNs.PSCBS # # @title "Normalizes copy numbers such that the whole-genome average total copy number is two" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Additional arguments passed to the normalization method.} # } # # \value{ # Returns a normalized AbstractCBS object of the same class as \code{fit}. # } # # @author # # \seealso{ # @seeclass. # } #*/########################################################################### setMethodS3("normalizeTotalCNs", "AbstractCBS", abstract=TRUE) PSCBS/R/CBS.EXTS.R0000644000176200001440000002654315000272342012646 0ustar liggesusers###########################################################################/** # @set class=DNAcopy # @RdocMethod as.CBS # # @title "Coerces a DNAcopy object to a CBS object" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{fit}{A \code{\link[DNAcopy:DNAcopy]{DNAcopy}}. object # (of the \pkg{DNAcopy} package.)} # \item{sample}{An index specifying which sample to extract, # if more than one exists.} # \item{...}{Not used.} # } # # \value{ # Returns a @see "CBS" object. # } # # @author "HB" # # \seealso{ # \code{\link[PSCBS:as.DNAcopy.CBS]{as.DNAcopy()}}. # For more information see \code{\link[DNAcopy:DNAcopy]{DNAcopy}}. # } # # @keyword internal #*/########################################################################### setMethodS3("as.CBS", "DNAcopy", function(fit, sample=1L, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- fit$data sample <- Arguments$getIndex(sample, max=ncol(data)-2L) sampleName <- colnames(data)[sample+2L] # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup the 'data' field # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- fit$data rownames <- rownames(data) data <- data.frame( chromosome = data$chrom, x = data$maploc, y = data[,sample+2L,drop=TRUE], stringsAsFactors=FALSE ) rownames(data) <- rownames # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup the 'output' field # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - output <- fit$output ID <- NULL; rm(list="ID") # To please R CMD check output <- subset(output, ID == sampleName) rownames <- rownames(output) output <- data.frame( chromosome = output$chrom, start = output$loc.start, end = output$loc.end, nbrOfLoci = as.integer(output$num.mark), mean = output$seg.mean, stringsAsFactors=FALSE ) rownames(output) <- rownames # Add chromosome splitter ats <- which(diff(output$chromosome) != 0) + 1L if (length(ats) > 0) { idxs <- seq_len(nrow(output)) values <- rep(NA_integer_, times=length(ats)) expand <- insert(idxs, ats=ats, values=values) # R.utils::insert() output <- output[expand,] rownames(output) <- NULL } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup up 'CBS' object # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (sampleName == "") sampleName <- NA_character_ res <- list() res$sampleName <- sampleName res$data <- data res$output <- output res$params <- list() class(res) <- class(CBS()) res }) # as.CBS() setMethodS3("extractTotalCNs", "CBS", function(fit, ...) { data <- getSegments(fit, ...) data[,c("mean", "nbrOfLoci"), drop=FALSE] }, protected=TRUE) setMethodS3("extractCNs", "CBS", function(fit, ...) { data <- extractTotalCNs(fit, ...) data <- data[,c("mean"), drop=FALSE] data <- as.matrix(data) data }, protected=TRUE) setMethodS3("extractChromosomes", "CBS", function(x, chromosomes, ...) { # To please R CMD check this <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'chromosomes': disallow <- c("NaN", "Inf") chromosomes <- Arguments$getIntegers(chromosomes, range=c(0,Inf), disallow=disallow) .stop_if_not(all(is.element(chromosomes, getChromosomes(this)))) # Always extract in order chromosomes <- unique(chromosomes) chromosomes <- sort(chromosomes) # Allocate results res <- this # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Locus data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chromosome <- NULL; rm(list="chromosome") # To please R CMD check data <- getLocusData(this) class <- class(data) class(data) <- "data.frame" data <- subset(data, chromosome %in% chromosomes) class(data) <- class res$data <- data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify rows to subset rows <- which(is.element(res$output$chromosome, chromosomes)) for (field in c("output", "segRows")) { res[[field]] <- res[[field]][rows,,drop=FALSE] } # Identify chromosome offsets data <- getLocusData(this) chrStarts <- match(getChromosomes(this), data$chromosome) chrEnds <- c(chrStarts[-1]-1L, nrow(data)) chrLengths <- chrEnds - chrStarts + 1L chrLengthsExcl <- chrLengths keep <- match(chromosomes, getChromosomes(this)) chrLengthsExcl[keep] <- 0L cumChrLengthsExcl <- cumsum(chrLengthsExcl) shifts <- cumChrLengthsExcl[keep] .stop_if_not(all(is.finite(shifts))) # Adjust indices for (cc in seq_along(chromosomes)) { chromosome <- chromosomes[cc] shift <- shifts[cc] # Nothing to do? if (shift == 0) next for (field in c("segRows")) { segRows <- res[[field]] rows <- which(res$output$chromosome == chromosome) segRows[rows,] <- segRows[rows,] - shift res[[field]] <- segRows } } res }, protected=TRUE) setMethodS3("subset", "CBS", function(x, chromlist=NULL, ...) { extractChromosomes(x, chromosomes=chromlist, ...) }, private=TRUE) ###########################################################################/** # @set "class=CBS" # @RdocMethod extractSegmentMeansByLocus # # @title "Extracts segments means at each locus" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to @seemethod "getLocusData".} # } # # \value{ # Returns a @numeric @vector of length \code{nbrOfLoci()}. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("extractSegmentMeansByLocus", "CBS", function(fit, ...) { data <- getLocusData(fit, ...) chromosome <- data$chromosome x <- data$x y <- data[,3] segs <- getSegments(fit) nbrOfSegments <- nrow(segs) nbrOfLoci <- nrow(data) # Get mean estimators estList <- getMeanEstimators(fit, "y") avgY <- estList$y yS <- y for (ss in seq_len(nbrOfSegments)) { seg <- segs[ss,] idxs <- which(seg$chromosome == chromosome & seg$start <= x & x <= seg$end) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) ySS <- y[idxs] ok <- is.finite(ySS) # Sanity check ## .stop_if_not(sum(ok) == seg$nbrOfLoci) # Not dealing with ties mu <- avgY(ySS[ok]) yS[idxs] <- mu } # for (ss ...) yS }, private=TRUE) # extractSegmentMeansByLocus() ###########################################################################/** # @set "class=CBS" # @RdocMethod estimateStandardDeviation # # @title "Estimates the whole-genome standard deviation of the signals" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{chromosomes}{An optional @vector specifying the subset of # chromosomes used for the estimate. If @NULL, all chromosomes are used.} # \item{method}{A @character string specifying the method used.} # \item{estimator}{A @character string or a @function specifying the # internal estimator.} # \item{na.rm}{If @TRUE, missing values are dropped, otherwise not.} # \item{weights}{An optional @double @vector of \code{nbrOfLoci()} # non-negative weights.} # \item{...}{Not used.} # } # # \value{ # Returns a non-negative @numeric scale. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("estimateStandardDeviation", "CBS", function(fit, chromosomes=NULL, method=c("diff", "res", "abs", "DNAcopy"), estimator=c("mad", "sd"), na.rm=TRUE, weights=NULL, ...) { # Local copies of DNAcopy functions DNAcopy_trimmed.variance <- .use("trimmed.variance", package="DNAcopy") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'chromosomes': if (!is.null(chromosomes)) { } # Argument 'method': method <- match.arg(method) # Argument 'estimator': estimator <- match.arg(estimator) # Argument 'weights': if (!is.null(weights)) { nbrOfLoci <- nbrOfLoci(fit) weights <- Arguments$getNumerics(weights, range=c(0,Inf), length=rep(nbrOfLoci, times=2)) } # Get the estimator function if (!is.null(weights)) { estimator <- sprintf("weighted %s", estimator) estimator <- R.utils::toCamelCase(estimator) } if (method == "DNAcopy") { estimatorFcn <- function(y, trim=0.025, ...) { sigma2 <- DNAcopy_trimmed.variance(y, trim=trim) sqrt(sigma2) } } else { estimatorFcn <- get(estimator, mode="function") } # Subset by chromosomes? if (!is.null(chromosomes)) { fit <- extractChromosomes(fit, chromosomes=chromosomes) } nbrOfLoci <- nbrOfLoci(fit) # Nothing to do? if (nbrOfLoci <= 1) { sigma <- NA_real_ attr(sigma, "nbrOfLoci") <- nbrOfLoci attr(sigma, "df") <- NA_integer_ return(sigma) } data <- getLocusData(fit) y <- data[,3] if (method == "diff") { dy <- diff(y) # Weighted estimator? if (!is.null(weights)) { # Calculate weights per pair weights <- (weights[1:(nbrOfLoci-1)]+weights[2:nbrOfLoci])/2 sigma <- estimatorFcn(dy, w=weights, na.rm=na.rm)/sqrt(2) } else { sigma <- estimatorFcn(dy, na.rm=na.rm)/sqrt(2) } df <- length(dy) } else if (method == "res") { yS <- extractSegmentMeansByLocus(fit) dy <- y - yS if (!is.null(weights)) { sigma <- estimatorFcn(dy, w=weights, na.rm=na.rm) } else { sigma <- estimatorFcn(dy, na.rm=na.rm) } df <- length(dy) } else if (method == "abs") { if (!is.null(weights)) { sigma <- estimatorFcn(y, w=weights, na.rm=na.rm) } else { sigma <- estimatorFcn(y, na.rm=na.rm) } df <- length(y) } else if (method == "DNAcopy") { if (na.rm) { y <- y[!is.na(y)] } sigma <- estimatorFcn(y, ...) df <- length(y) } else { stop("Method no implemented: ", method) } attr(sigma, "nbrOfLoci") <- nbrOfLoci attr(sigma, "df") <- df sigma }) # estimateStandardDeviation() setMethodS3("getChromosomeRanges", "CBS", function(fit, ...) { # To please R CMD check, cf. subset() chromosome <- NULL; rm(list="chromosome") segs <- getSegments(fit, splitters=FALSE) chromosomes <- sort(unique(segs$chromosome)) # Allocate naValue <- NA_real_ res <- matrix(naValue, nrow=length(chromosomes), ncol=3) rownames(res) <- chromosomes colnames(res) <- c("start", "end", "length") # Get start and end of each chromosome. for (ii in seq_len(nrow(res))) { chr <- chromosomes[ii] segsII <- subset(segs, chromosome == chr) res[ii,"start"] <- min(segsII$start, na.rm=TRUE) res[ii,"end"] <- max(segsII$end, na.rm=TRUE) } # for (ii ...) res[,"length"] <- res[,"end"] - res[,"start"] + 1L # Sanity check .stop_if_not(nrow(res) == length(chromosomes)) res <- as.data.frame(res) res <- cbind(chromosome=chromosomes, res) res }, protected=TRUE) # getChromosomeRanges() PSCBS/R/PairedPSCBS.PRUNE.R0000644000176200001440000000020414564051545014344 0ustar liggesuserssetMethodS3("seqOfSegmentsByDP", "PairedPSCBS", function(fit, by=c("CT", "rho"), ...) { NextMethod("seqOfSegmentsByDP", by=by) }) PSCBS/R/PairedPSCBS.updateMeans.R0000644000176200001440000001734414564051545015736 0ustar liggesuserssetMethodS3("updateMeans", "PairedPSCBS", function(fit, from=c("loci", "segments"), adjustFor=NULL, ..., avgTCN=c("asis", "mean", "median"), avgDH=c("asis", "mean", "median"), clear=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'from': from <- match.arg(from) # Argument 'adjustFor': if (!is.null(adjustFor)) { adjustFor <- Arguments$getCharacters(adjustFor) adjustFor <- tolower(adjustFor) knownValues <- c("ab", "loh", "roh") adjustFor <- match.arg(adjustFor, choices=knownValues, several.ok=TRUE) } # Argument 'avgTCN' & 'avgDH': avgTCN <- match.arg(avgTCN) avgDH <- match.arg(avgDH) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating mean level estimates") verbose && cat(verbose, "Adjusting for:") verbose && print(verbose, adjustFor) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up averaging functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (avgTCN == "asis" || avgDH == "asis") { est <- fit$params$meanEstimators if (avgTCN == "asis") { avgTCN <- est$tcn if (is.null(avgTCN)) avgTCN <- "mean" avgTCN <- match.arg(avgTCN) } if (avgDH == "asis") { avgDH <- est$dh if (is.null(avgDH)) avgDH <- "mean" avgDH <- match.arg(avgDH) } } avgList <- list( tcn = get(avgTCN, mode="function"), dh = get(avgDH, mode="function") ) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- getSegments(fit, splitters=TRUE) segRows <- list(tcn=fit$tcnSegRows, dh=fit$dhSegRows) nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Assert that adjustments can be made # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.element("ab", adjustFor)) { if (!is.element("abCall", names(segs))) { adjustFor <- setdiff(adjustFor, "ab") stop("Cannot adjust for AB, because they haven't been called.") } } if (is.element("loh", adjustFor)) { if (!is.element("lohCall", names(segs))) { adjustFor <- setdiff(adjustFor, "loh") stop("Cannot adjust for LOH, because they haven't been called.") } } if (is.element("roh", adjustFor)) { if (!is.element("rohCall", names(segs))) { adjustFor <- setdiff(adjustFor, "roh") stop("Cannot adjust for ROH, because they haven't been called.") } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update the (TCN,DH) mean levels from locus-level data? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (from == "loci") { data <- getLocusData(fit) chromosome <- data$chromosome x <- data$x CT <- data$CT rho <- data$rho isSplitter <- isSegmentSplitter(fit) for (ss in seq_len(nbrOfSegments)[!isSplitter]) { verbose && enter(verbose, sprintf("Segment %d of %d", ss, nbrOfSegments)) seg <- segs[ss,] verbose && print(verbose, seg) chr <- seg[["chromosome"]] chrTag <- sprintf("chr%02d", chr) for (what in c("tcn", "dh")) { segRow <- segRows[[what]][ss,] # (a) A splitter - nothing todo? if (!is.finite(segRow[[1]]) || !is.finite(segRow[[2]])) { next } # (b) Identify units (loci) units <- segRow[[1]]:segRow[[2]] # (c) Adjust for missing values if (what == "tcn") { value <- CT } else if (what == "dh") { value <- rho } keep <- which(!is.na(value[units])) units <- units[keep] # (d) Update mean avgFUN <- avgList[[what]] gamma <- avgFUN(value[units]) # Sanity check .stop_if_not(length(units) == 0 || !is.na(gamma)) # Update the segment boundaries, estimates and counts key <- paste(what, "Mean", sep="") seg[[key]] <- gamma } verbose && print(verbose, seg) segs[ss,] <- seg verbose && exit(verbose) } # for (ss ...) } # if (from ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Adjust segment means from various types of calls # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (length(adjustFor) > 0) { verbose && enter(verbose, "Adjusting segment means") verbose && cat(verbose, "Adjusting for:") verbose && print(verbose, adjustFor) if (is.element("ab", adjustFor)) { verbose && enter(verbose, "Adjusting for AB") calls <- segs$abCall segs$dhMean[calls] <- 0 verbose && exit(verbose) } if (is.element("loh", adjustFor)) { verbose && enter(verbose, "Adjusting for LOH") calls <- segs$lohCall segs$dhMean[calls] <- 1 verbose && exit(verbose) } if (is.element("roh", adjustFor)) { verbose && enter(verbose, "Adjusting for ROH") calls <- segs$rohCall segs$dhMean[calls] <- NA_real_ verbose && exit(verbose) } verbose && exit(verbose) } # if (length(adjustFor) > 0) # Update fit$output <- segs fit <- setMeanEstimators(fit, tcn=avgTCN, dh=avgDH) if (clear) { fit <- clearBootstrapSummaries(fit) } # Update (C1,C2) mean levels fit <- updateMeansC1C2(fit, verbose=verbose) verbose && exit(verbose) fit }, private=TRUE) # updateMeans() setMethodS3("updateMeansC1C2", "PairedPSCBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating (C1,C2) segment mean levels") segs <- getSegments(fit) if (nrow(segs) > 0L) { tcn <- segs$tcnMean dh <- segs$dhMean C1 <- 1/2*(1-dh)*tcn C2 <- tcn - C1 segs$c1Mean <- C1 segs$c2Mean <- C2 # Preserve (C1,C2) swaps / change-point flips? swap <- segs$c1c2Swap if (!is.null(swap)) { swap <- which(swap) if (length(swap) > 0L) { segs[swap, c("c1Mean","c2Mean")] <- segs[swap, c("c2Mean","c1Mean")] } } fit$output <- segs } verbose && exit(verbose) fit }, protected=TRUE) # updateMeansC1C2() ############################################################################## # HISTORY # 2014-03-26 # o BUG FIX: updateMeansC1C2() for PairedPSCBS did not handle missing # values (=splitters) in the 'c1c2Swap' field. # 2014-03-25 # o BUG FIX: updateMeans() for PairedPSCBS and NonPairedPSCBS returned the # incorrect DH segment levels for region in AB if adjustFor="ab" and # likewise for segments in LOH if adjustFor="loh". # 2013-11-23 # o Now updateMeans(..., clear=TRUE) clears bootstrap summaries, otherwise # not. # 2013-10-26 # o Now updateMeans() for PairedPSCBS always clears the bootstrap summaries. # o Added updateMeansC1C2(). # o updateMeans() for PairedPSCBS did not preserve the (C1,C2) swaps. # 2012-04-21 # o CLEANUP: Removed unused objects in updateMeans(). # 2011-11-12 # o Added arguments 'from' and 'adjustFor' to updateMeans(). # 2011-01-16 # o BUG FIX: updateMeans() save to the incorrect column names. # 2011-01-12 # o Added updateMeans() for PairedPSCBS. ############################################################################## PSCBS/R/CBS.joinSegments.R0000644000176200001440000001114614564051545014537 0ustar liggesusers###########################################################################/** # @set "class=CBS" # @RdocMethod joinSegments # # @title "Joins neighboring segments such that there is no gap in between them" # # \description{ # @get "title". # For instance, consider two neighboring segments [x1,x2] and [x3,x4] # with x1 < x2 < x3 < x4. After join the segments, they are # [x1,x23] and [x23,x4] where x23 = (x2 + x3)/2. # } # # @synopsis # # \arguments{ # \item{range}{(optional) A @numeric @vector of length two.} # \item{verbose}{See @see "R.utils::Verbose".} # \item{...}{Not used.} # } # # \value{ # Returns an updated @see "CBS" object. # } # # \details{ # This function assumes only chromosome exists. # If more, an error will be thrown. # } # # @author "HB" # # @keyword IO # @keyword internal #*/########################################################################### setMethodS3("joinSegments", "CBS", function(fit, range=NULL, verbose=FALSE, ...) { R_SANITY_CHECK <- TRUE # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chromosomes <- getChromosomes(fit) nbrOfChrs <- length(chromosomes) # Argument 'range': if (!is.null(range)) { if (nbrOfChrs > 1L) { stop("Argument 'range' cannot be given when 'fit' contains multiple chromosomes.") } range <- Arguments$getDoubles(range, length=c(2,2)) .stop_if_not(range[2] >= range[1]) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Joining segments") segs <- getSegments(fit, splitters=TRUE) verbose && cat(verbose, "Segments:") verbose && print(verbose, segs) verbose && cat(verbose, "Chromosomes:") verbose && print(verbose, chromosomes) verbose && cat(verbose, "Range:") verbose && print(verbose, range) nbrOfSegs <- nrow(segs) if (nbrOfSegs > 1) { verbose && enter(verbose, "Centering change points") prevSeg <- segs[1L,] for (ss in 2:nbrOfSegs) { currSeg <- segs[ss,] ## New chromosome? if (!identical(currSeg$chromosome, prevSeg$chromosome)) { ## Skip splitters if (is.na(currSeg$chromosome)) next prevSeg <- currSeg next } currStart <- currSeg[,"start"] prevEnd <- prevSeg[,"end"] # Sanity check (will give an error if more than one chromosome) if (R_SANITY_CHECK) { .stop_if_not(all(currStart >= prevEnd, na.rm=TRUE)) } # Center CP xMid <- (prevEnd + currStart) / 2 # Move previous end and current start to this centered CP segs[ss,"start"] <- xMid segs[ss-1L,"end"] <- xMid prevSeg <- currSeg } # for (ss ...) verbose && exit(verbose) # Sanity checks if (R_SANITY_CHECK) { .stop_if_not(all(segs$start[-1] >= segs$end[-nbrOfSegs], na.rm=TRUE)) .stop_if_not(all(diff(segs$start) >= 0, na.rm=TRUE)) ## FIXME: > 0 .stop_if_not(all(diff(segs$end) >= 0, na.rm=TRUE)) ## FIXME: > 0 } # if (R_SANITY_CHECK) if (nbrOfSegs > 6) { verbose && print(verbose, head(segs)) verbose && print(verbose, tail(segs)) } else { verbose && print(verbose, segs) } } # if (nbrOfSegs > 1) if (!is.null(range)) { verbose && enter(verbose, "Adjust for 'range'") verbose && cat(verbose, "Range:") verbose && print(verbose, range) xMin <- min(range, na.rm=TRUE) xMax <- max(range, na.rm=TRUE) if (nbrOfSegs > 0) { # Sanity checks if (R_SANITY_CHECK) { .stop_if_not(xMin <= segs[1L,"start"]) .stop_if_not(segs[1L,"end"] <= xMax) } segs[1L,"start"] <- xMin segs[nbrOfSegs,"end"] <- xMax # Sanity checks if (R_SANITY_CHECK) { .stop_if_not(all(segs$start[-1] >= segs$end[-nbrOfSegs], na.rm=TRUE)) .stop_if_not(all(diff(segs$start) >= 0, na.rm=TRUE)) ## FIXME: > 0 .stop_if_not(all(diff(segs$end) >= 0, na.rm=TRUE)) ## FIXME: > 0 } if (nbrOfSegs > 6) { verbose && print(verbose, head(segs)) verbose && print(verbose, tail(segs)) } else { verbose && print(verbose, segs) } } # if (nbrOfSegs > 0) verbose && exit(verbose) } # if (!is.null(range)) fit <- setSegments(fit, segs, splitters=TRUE) segs <- getSegments(fit, splitters=FALSE) if (nbrOfSegs > 6) { verbose && print(verbose, head(segs)) verbose && print(verbose, tail(segs)) } else { verbose && print(verbose, segs) } verbose && exit(verbose) fit }, private=TRUE) # joinSegments() PSCBS/R/CBS.R0000644000176200001440000004100314564051545012066 0ustar liggesusers###########################################################################/** # @RdocClass CBS # # @title "The CBS class" # # \description{ # A CBS object holds results from the # Circular Binary Segmentation (CBS) method # for \emph{one} sample for one or more chromosomes. # # @classhierarchy # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to the constructor of @see "AbstractCBS".} # } # # \section{Fields and Methods}{ # @allmethods "public" # } # # \section{Difference to DNAcopy object}{ # A CBS object is similar to DNAcopy objects with the major # difference that a CBS object holds only one sample, whereas # a DNAcopy object can hold more than one sample. # } # # \section{See also}{ # The @see "segmentByCBS" method returns an object of this class. # } # # @author "HB" #*/########################################################################### setConstructorS3("CBS", function(...) { extend(AbstractCBS(list(data=NULL, output=NULL), ...), "CBS") }) setMethodS3("all.equal", "CBS", function(target, current, check.attributes=FALSE, ...) { # Compare class attributes res <- all.equal(class(target), class(current)) if (!isTRUE(res)) { return(res) } # WORKAROUND: segmentByCBS() return getSegments(fit)$id without NA:s for # splitters, unless append() is used. # TO DO: Fix segmentByCBS() /HB 2011-10-08 segs <- getSegments(target) if (nrow(segs) > 0) { isSplitter <- isSegmentSplitter(target) segs[isSplitter, "sampleName"] <- NA target$output <- segs } segs <- getSegments(current) if (nrow(segs) > 0) { isSplitter <- isSegmentSplitter(current) segs[isSplitter, "sampleName"] <- NA current$output <- segs } # NOTE: Here arguments 'target' and 'current' are lists and does not # have to be passed explicitly (although they have been modified). # If passed explicity, note that they must be named *and* that the # first/dispatch argument have to be passed as 'object=target' # (and never as 'target=target'). /HB 2014-02-03 NextMethod("all.equal", object=target, current=current, check.attributes=check.attributes) }, protected=TRUE) ###########################################################################/** # @RdocMethod as.data.frame # # @title "Gets the table of segments" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a @data.frame, where each row corresponds to # a unique segment. # } # # @author # # \seealso{ # Utilizes @seemethod "getSegments". # @seeclass. # } # # @keyword internal #*/########################################################################### setMethodS3("as.character", "CBS", function(x, ...) { # To please R CMD check fit <- x s <- sprintf("%s:", class(fit)[1]) s <- c(s, sprintf("Sample name: %s", getSampleName(fit))) s <- c(s, sprintf("Signal type: %s", getSignalType(fit))) s <- c(s, sprintf("Number of segments: %d", nbrOfSegments(fit))) s <- c(s, sprintf("Number of loci: %d", nbrOfLoci(fit))) n <- getSegments(fit)$nbrOfLoci q <- quantile(n, probs=c(0.00, 0.05, 0.25, 0.50, 0.75, 0.95, 1.00), na.rm=TRUE) qs <- sprintf("%g [%s]", q, names(q)) s <- c(s, sprintf("Number of loci per segment: %s", paste(qs, collapse=", "))) chrs <- getChromosomes(fit) s <- c(s, sprintf("Chromosomes: [%d] %s", length(chrs), hpaste(chrs))) s <- c(s, sprintf("Standard deviation: %g", estimateStandardDeviation(fit))) tt <- grep("Call$", colnames(getLocusData(fit)), value=TRUE) s <- c(s, sprintf("Locus calls: [%d] %s", length(tt), hpaste(tt))) segs <- getSegments(fit) callCols <- grep("Call$", colnames(segs), value=TRUE) callTypes <- gsub("Call$", "", callCols) s <- c(s, sprintf("Types of segment calls: [%d] %s", length(callTypes), hpaste(callTypes))) for (kk in seq_along(callCols)) { key <- callCols[kk] type <- callTypes[kk] n <- sum(segs[,key], na.rm=TRUE) if (type == "loss") { nC <- sum(isWholeChromosomeLost(fit)) } else if (type == "gain") { nC <- sum(isWholeChromosomeGained(fit)) } else { nC <- NA } s <- c(s, sprintf("Number of chromosomes (segments) called '%s': %d (%d)", type, nC, n)) } GenericSummary(s) }, protected=TRUE) setMethodS3("as.data.frame", "CBS", function(x, ...) { getSegments(x, splitters=FALSE, ...) }, protected=TRUE) setMethodS3("getSignalType", "CBS", function(fit, ...) { type <- fit$signalType if (is.null(type)) type <- NA_character_ type }, protected=TRUE) setMethodS3("signalType", "CBS", function(fit, ...) { getSignalType(fit) }, protected=TRUE) "signalType<-" <- function(x, value) { UseMethod("signalType<-") } setMethodS3("signalType<-", "CBS", function(x, value) { fit <- x # Argument 'value': value <- Arguments$getCharacter(value) fit$signalType <- value fit }, private=TRUE, addVarArgs=FALSE) setMethodS3("getLocusSignalNames", "CBS", function(fit, ...) { data <- fit$data names <- colnames(data) if (is.element("y", names)) { return("y") } else if (is.element("CT", names)) { return("CT") } stop("INTERNAL ERROR: Unknown locus signal names: ", paste(names, collapse=", ")) }, protected=TRUE) setMethodS3("getSegmentTrackPrefixes", "CBS", function(fit, ...) { c("") }, protected=TRUE) setMethodS3("getLocusData", "CBS", function(fit, indices=NULL, addCalls=NULL, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'indices': if (!is.null(indices)) { indices <- Arguments$getIndices(indices) } # Argument 'addCalls': if (is.logical(addCalls)) { addCalls <- Arguments$getLogical(addCalls) if (!addCalls) { addCalls <- NULL } } else { addCalls <- Arguments$getCharacters(addCalls) } data <- fit$data # Append segment calls? if (length(addCalls) > 0) { callsL <- extractCallsByLocus(fit) if (is.character(addCalls)) { callsL <- callsL[,addCalls] } # Sanity check .stop_if_not(nrow(callsL) == nrow(data)) data <- cbind(data, callsL) } # Return requested indices if (!is.null(indices)) { # Map of final indices to current indices map <- match(indices, data$index) # Extract/expand... data <- data[map,] rownames(data) <- NULL # Sanity check .stop_if_not(nrow(data) == length(indices)) } data }, private=TRUE) # getLocusData() setMethodS3("isSegmentSplitter", "CBS", function(fit, ...) { segs <- fit$output isSplitter <- lapply(segs[-1], FUN=is.na) isSplitter <- Reduce("&", isSplitter) isSplitter }, protected=TRUE) setMethodS3("getSegments", "CBS", function(fit, simplify=FALSE, splitters=TRUE, addGaps=FALSE, ...) { # Argument 'splitters': splitters <- Arguments$getLogical(splitters) segs <- fit$output isSplitter <- isSegmentSplitter(fit) # Add 'sampleName' column? if (nrow(segs) > 0) { sampleName <- rep(getSampleName(fit), times=nrow(segs)) sampleName[isSplitter] <- NA_character_ if (!is.element("sampleName", colnames(segs))) { segs <- cbind(sampleName=I(sampleName), segs) } else { segs[,"sampleName"] <- sampleName } } # Drop chromosome splitters? if (!splitters) { segs <- segs[!isSplitter,] } # Add splitters for "gaps"... if (splitters && addGaps) { # Chromosome gaps n <- nrow(segs) chrs <- segs$chromosome gapsAfter <- which(diff(chrs) != 0L) gapsAfter <- gapsAfter[!is.na(chrs[gapsAfter])] nGaps <- length(gapsAfter) if (nGaps > 0L) { idxs <- seq_len(n) values <- rep(NA_integer_, times=nGaps) idxs <- insert(idxs, ats=gapsAfter+1L, values=values) segs <- segs[idxs,] } # Other gaps n <- nrow(segs) chrs <- segs$chromosome starts <- segs$tcnStart[-1L] ends <- segs$tcnEnd[-n] gapsAfter <- which(starts != ends) onSameChr <- (chrs[gapsAfter+1L] == chrs[gapsAfter] ) gapsAfter <- gapsAfter[onSameChr] nGaps <- length(gapsAfter) if (nGaps > 0L) { idxs <- seq_len(n) values <- rep(NA_integer_, times=nGaps) idxs <- insert(idxs, ats=gapsAfter+1L, values=values) segs <- segs[idxs,] } } segs }, private=TRUE) setMethodS3("getChangePoints", "CBS", function(fit, ...) { # Already available? cps <- fit$changepoints if (!is.null(cps)) return(cps) segs <- getSegments(fit, splitters=TRUE) tcn <- segs[["mean"]] n <- length(tcn) # Calculate observed (d) data D <- tcn[-n] - tcn[-1L] cps <- data.frame( d = D ) cps }, private=TRUE) # getChangePoints() setMethodS3("updateBoundaries", "CBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating boundaries") verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fit, splitters=FALSE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit, splitters=TRUE) segRows <- fit$segRows nbrOfSegments <- nrow(segs) chromosome <- data$chromosome x <- data$x y <- data$y w <- data$w hasWeights <- !is.null(w) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - for (ss in seq_len(nbrOfSegments)) { verbose && enter(verbose, sprintf("Segment %d of %d", ss, nbrOfSegments)) segRow <- segRows[ss,] seg <- segs[ss,] # A splitter - nothing todo? if (is.na(segRow[[1]]) && is.na(segRow[[2]])) { next } # (a) Identify units (loci) units <- segRow[[1]]:segRow[[2]] verbose && cat(verbose, "Loci:") verbose && str(verbose, units) # (b) Extract signals ySS <- y[units] xSS <- x[units] cSS <- chromosome[units] if (hasWeights) { wSS <- w[units] } # (c) Drop missing values keep <- (!is.na(ySS) & !is.na(xSS) & !is.na(cSS)) if (hasWeights) { keep <- keep & (!is.na(wSS) & wSS > 0) } keep <- which(keep) ySS <- ySS[keep] xSS <- xSS[keep] cSS <- cSS[keep] if (hasWeights) { wSS <- wSS[keep] } units <- units[keep] verbose && cat(verbose, "Loci (non-missing):") verbose && str(verbose, units) # (d) Identify (chromosome, start, stop) .stop_if_not(all(cSS == cSS[1])) cSS <- cSS[1] xRange <- range(xSS, na.rm=TRUE) verbose && cat(verbose, "Range:") verbose && print(verbose, xRange) # (e) Update segment information seg$chromosome <- cSS seg$start <- xRange[1] seg$end <- xRange[2] segs[ss,] <- seg verbose && exit(verbose) } # for (ss ...) # Update results res <- fit res$output <- segs # Rejoin segments? if (isTRUE(res$params$joinSegments)) { res <- joinSegments(res, verbose=less(verbose,10)) } verbose && exit(verbose) res }, protected=TRUE) # updateBoundaries() setMethodS3("updateMeans", "CBS", function(fit, ..., avg=c("asis", "mean", "median"), verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'avg': avg <- match.arg(avg) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating mean level estimates") verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fit, splitters=FALSE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit, splitters=TRUE) segRows <- fit$segRows nbrOfSegments <- nrow(segs) chromosome <- data$chromosome x <- data$x y <- data$y w <- data$w hasWeights <- !is.null(w) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up averaging functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (avg == "asis") { est <- fit$params$meanEstimators avg <- est$y if (is.null(avg)) avg <- "mean" avg <- match.arg(avg) } if (hasWeights) { if(avg == "mean") { avgFUN <- weighted.mean } else if(avg == "median") { avgFUN <- weightedMedian } else { stop("Value of argument 'avg' is not supported with weights: ", avg) } } else { avgFUN <- get(avg, mode="function") } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - for (ss in seq_len(nbrOfSegments)) { verbose && enter(verbose, sprintf("Segment %d of %d", ss, nbrOfSegments)) segRow <- segRows[ss,] seg <- segs[ss,] # A splitter - nothing todo? if (!is.finite(segRow[[1]]) || !is.finite(segRow[[2]])) { next } # (a) Identify units (loci) units <- segRow[[1]]:segRow[[2]] # (b) Extract signals ySS <- y[units] if (hasWeights) { wSS <- w[units] } # (c) Drop missing values keep <- (!is.na(ySS)) if (hasWeights) { keep <- keep & (!is.na(wSS) & wSS > 0) } keep <- which(keep) ySS <- ySS[keep] if (hasWeights) { wSS <- wSS[keep] } units <- units[keep] nbrOfLoci <- length(units) # (d) Update mean if (hasWeights) { wSS <- wSS / sum(wSS) gamma <- avgFUN(ySS, w=wSS) } else { gamma <- avgFUN(ySS) } # Sanity check .stop_if_not(nbrOfLoci == 0 || !is.na(gamma)) # (d) Update the segment statistics seg$mean <- gamma seg$nbrOfLoci <- nbrOfLoci segs[ss,] <- seg verbose && exit(verbose) } # for (ss ...) # Return results res <- fit res$output <- segs res <- setMeanEstimators(res, y=avg) verbose && exit(verbose) res }, protected=TRUE) # updateMeans() setMethodS3("resegment", "CBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Resegmenting a ", class(fit)[1], " object") segFcnName <- "segmentByCBS" segFcn <- getMethodS3(segFcnName, "default") # Use the locus-level data of the segmentation object data <- getLocusData(fit) class(data) <- "data.frame" drop <- c("index") keep <- !is.element(colnames(data), drop) data <- data[,keep] verbose && str(verbose, data) verbose && cat(verbose, "Number of loci: ", nrow(data)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup arguments to be passed # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Overriding default arguments") # (a) The default arguments formals <- formals(segFcn) formals <- formals[!sapply(formals, FUN=is.language)] formals <- formals[!sapply(formals, FUN=is.name)] drop <- c("chromosome", "x", "y", "w", "...") keep <- !is.element(names(formals), drop) formals <- formals[keep] # (b) The arguments used in previous fit params <- fit$params keep <- is.element(names(params), names(formals)) params <- params[keep] # (c) The arguments in '...' userArgs <- list(..., verbose=verbose) # (d) Merge args <- formals args2 <- c(params, userArgs) for (kk in seq_along(args2)) { value <- args2[[kk]] if (!is.null(value)) { key <- names(args2)[kk] if (!is.null(key)) { args[[key]] <- value } else { args <- c(args, list(value)) } } } # for (key ...) verbose && str(verbose, args[names(args) != "verbose"]) args <- c(list(data), args) verbose && cat(verbose, "Arguments with data:") verbose && str(verbose, args[names(args) != "verbose"]) verbose && exit(verbose) verbose && enter(verbose, sprintf("Calling %s()", segFcnName)) fit <- do.call(segFcnName, args) verbose && exit(verbose) verbose && exit(verbose) fit }, protected=TRUE) # resegment() PSCBS/R/drawLevels.DNAcopy.R0000644000176200001440000000063114564051545015065 0ustar liggesuserssetMethodS3("drawLevels", "DNAcopy", function(fit, field=c("seg.mean", "tcn.mean", "dh.mean"), xScale=1, col="red", lwd=3, ...) { field <- match.arg(field) segments <- fit$output[,c("loc.start", "loc.end", field)] apply(segments, MARGIN=1, FUN=function(seg) { x <- c(seg[["loc.start"]], seg[["loc.end"]]) y <- rep(seg[[field]], times=2) lines(x=xScale*x, y=y, col=col, lwd=lwd, ...) }) }) PSCBS/R/PairedPSCBS.EXTS.R0000644000176200001440000003455014564051545014251 0ustar liggesuserssetMethodS3("shiftTCN", "PairedPSCBS", function(fit, shift, update=TRUE, ...) { # Argument 'shift': shift <- Arguments$getDouble(shift, disallow=c("NA", "NaN", "Inf")) data <- getLocusData(fit) data$CT <- data$CT + shift fit$data <- data # Not needed anymore data <- NULL if (update) { fit <- updateMeans(fit, ...) } fit }, protected=TRUE) setMethodS3("bootstrapCIs", "PairedPSCBS", function(fit, ...) { # ... }, private=TRUE) ###########################################################################/** # @set "class=PairedPSCBS" # @RdocMethod extractTCNAndDHs # # @title "Extract TCN and DH mean levels per segment" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Arguments passed to \code{getSegments()}.} # } # # \value{ # Returns a @data.frame. # } # # @author "HB" # # \seealso{ # @seemethod "extractMinorMajorCNs". # @seeclass # } #*/########################################################################### setMethodS3("extractTCNAndDHs", "PairedPSCBS", function(fit, ...) { segs <- getSegments(fit, ...) .stop_if_not(!is.null(segs)) data <- segs[,c("tcnMean", "dhMean", "tcnNbrOfLoci", "dhNbrOfLoci"), drop=FALSE] data }, protected=TRUE) ###########################################################################/** # @set "class=PairedPSCBS" # @RdocMethod extractMinorMajorCNs # @aliasmethod extractC1C2 # # @title "Extract minor and major copy-number mean levels per segment" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns a @data.frame. # } # # @author "HB" # # \seealso{ # @seemethod "extractTCNAndDHs" # @seeclass # } #*/########################################################################### setMethodS3("extractMinorMajorCNs", "PairedPSCBS", function(fit, ...) { data <- extractTCNAndDHs(fit, ...) gamma <- data[,1L] rho <- data[,2L] C1 <- 1/2*(1-rho)*gamma C2 <- gamma - C1 data[,1L] <- C1 data[,2L] <- C2 colnames(data)[1:2] <- c("C1", "C2") # Swap (C1,C2)? segs <- getSegments(fit, ...) flipped <- segs$c1c2Swap if (!is.null(flipped)) { idxs <- which(flipped) if (length(idxs) > 0L) { data[idxs,1:2] <- data[idxs,2:1] } } data }, protected=TRUE) setMethodS3("extractC1C2", "PairedPSCBS", function(...) { extractMinorMajorCNs(...) }, protected=TRUE) setMethodS3("extractCNs", "PairedPSCBS", function(fit, splitters=TRUE, ...) { data <- extractC1C2(fit, splitters=splitters, ...) data[,c("C1", "C2"), drop=FALSE] }) setMethodS3("extractDeltaC1C2", "PairedPSCBS", function(...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - X <- extractC1C2(..., splitters=TRUE, addGaps=TRUE) # (C1,C2) C1C2 <- X[,1:2,drop=FALSE] # Number of TCN and DH data points counts <- X[,3:4, drop=FALSE] # Not needed anymore X <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calculate (dC1,dC2) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # (dC1, dC2) dC1C2 <- colDiffs(C1C2, useNames = FALSE) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Change-point weights # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Region weights from DH counts w <- counts[,2,drop=TRUE] w <- sqrt(w) w <- w / sum(w, na.rm=TRUE) # (a) Smallest of the two flanking (DH) counts cpw <- cbind(w[1:(length(w)-1)], w[2:length(w)]) cpw <- rowMins(cpw, na.rm=TRUE, useNames=FALSE) cpw[is.infinite(cpw)] <- NA cpw <- sqrt(cpw) cpwMin <- cpw / sum(cpw, na.rm=TRUE) # (b) Sum of region weights cpw <- w[1:(length(w)-1)] + w[2:length(w)] cpwAvg <- cpw / sum(cpw, na.rm=TRUE) cbind(dC1=dC1C2[,1], dC2=dC1C2[,2], wMin=cpwMin, wAvg=cpwAvg) }, protected=TRUE) setMethodS3("postsegmentTCN", "PairedPSCBS", function(fit, ..., force=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Post-segmenting TCNs") flavor <- fit$params$flavor if (!force && regexpr("&", flavor, fixed=TRUE) != -1) { verbose && cat(verbose, "Nothing to do. Already postsegmentTCN:ed: ", flavor) verbose && exit(verbose) return(fit) } joinSegments <- fit$params$joinSegments if (!joinSegments) { stop("Postsegmentation of TCNs is only implemented for the case when joinSegments=TRUE: ", joinSegments) } # Get mean estimators estList <- getMeanEstimators(fit, "tcn") avgTCN <- estList$tcn # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the data and segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit) keep <- is.finite(segs$chromosome) segs <- segs[keep,,drop=FALSE] tcnSegRows <- fit$tcnSegRows[keep,,drop=FALSE] dhSegRows <- fit$dhSegRows[keep,,drop=FALSE] # Sanity check .stop_if_not(nrow(dhSegRows) == nrow(tcnSegRows)) .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) # .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRows[,1] <= dhSegRows[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRows[-nrow(dhSegRows),2] < dhSegRows[-1,1], na.rm=TRUE)) nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments) chromosome <- data$chromosome x <- data$x CT <- data$CT muN <- data$muN rho <- data$rho hasDH <- !is.null(rho) if (hasDH) { isHet <- !is.na(rho) isSnp <- isHet } else { isSnp <- !is.na(muN) isHet <- (isSnp & (muN == 1/2)) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update the TCN segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chromosomes <- getChromosomes(fit) nbrOfChromosomes <- length(chromosomes) verbose && cat(verbose, "Number of chromosomes: ", nbrOfChromosomes) verbose && print(verbose, chromosomes) for (cc in seq_len(nbrOfChromosomes)) { chr <- chromosomes[cc] chrTag <- sprintf("chr%02d", chr) verbose && enter(verbose, sprintf("Chromosome %d ('%s') of %d", cc, chrTag, nbrOfChromosomes)) rows <- which(is.element(segs[["chromosome"]], chr)) verbose && cat(verbose, "Rows:") verbose && print(verbose, rows) segsCC <- segs[rows,,drop=FALSE] tcnSegRowsCC <- tcnSegRows[rows,,drop=FALSE] dhSegRowsCC <- dhSegRows[rows,,drop=FALSE] nbrOfSegmentsCC <- nrow(segsCC) verbose && cat(verbose, "Number of segments: ", nbrOfSegmentsCC) tcnIds <- sort(unique(segsCC[["tcnId"]])) I <- length(tcnIds) for (ii in seq_len(I)) { tcnId <- tcnIds[ii] verbose && enter(verbose, sprintf("TCN segment #%d ('%s') of %d", ii, tcnId, I)) rowsII <- which(segsCC[["tcnId"]] == tcnId) J <- length(rowsII) # Nothing todo? if (!force && J == 1) { verbose && cat(verbose, "Nothing todo. Only one DH segmentation. Skipping.") verbose && exit(verbose) next } verbose && cat(verbose, "Rows:") verbose && print(verbose, rowsII) segsII <- segsCC[rowsII,,drop=FALSE] tcnSegRowsII <- tcnSegRowsCC[rowsII,,drop=FALSE] dhSegRowsII <- dhSegRowsCC[rowsII,,drop=FALSE] verbose && cat(verbose, "TCN & DH segRows before:") verbose && print(verbose, cbind(tcn=tcnSegRowsII, dh=dhSegRowsII)) segRowsRange <- range(c(tcnSegRowsII, dhSegRowsII), na.rm=TRUE) verbose && printf(verbose, "Range [%d,%d]\n", segRowsRange[1], segRowsRange[2]) tcnSegRowsIIBefore <- tcnSegRowsII nbrOfTCNsBefore <- segsII[1,"tcnNbrOfLoci"] # Sanity check .stop_if_not(diff(segRowsRange)+1L == nbrOfTCNsBefore) for (jj in seq_len(J)) { verbose && enter(verbose, sprintf("DH segment #%d of %d", jj, J)) seg <- segsII[jj,,drop=FALSE] tcnSegRow <- unlist(tcnSegRowsII[jj,,drop=FALSE], use.names=FALSE) dhSegRow <- unlist(dhSegRowsII[jj,,drop=FALSE], use.names=FALSE) # Sanity check .stop_if_not(all(is.na(tcnSegRow)) || (tcnSegRow[1] <= tcnSegRow[2])) .stop_if_not(all(is.na(dhSegRow)) || (dhSegRow[1] <= dhSegRow[2])) # Sanity check idxsTCN <- tcnSegRow[1]:tcnSegRow[2] nbrOfTCNs <- sum(!is.na(CT[idxsTCN])) .stop_if_not(nbrOfTCNs == nbrOfTCNsBefore) if (joinSegments) { # (a) The TCN segment should have identical (start,end) boundaries as the DH region xStart <- seg[["dhStart"]] xEnd <- seg[["dhEnd"]] verbose && printf(verbose, "[xStart,xEnd] = [%.0f,%.0f]\n", xStart, xEnd) .stop_if_not(xStart <= xEnd) # (b) Identify units units <- which(chromosome == chr & xStart <= x & x <= xEnd) # (c) Drop units that are outside both the TCN and DH segments keep <- (segRowsRange[1] <= units & units <= segRowsRange[2]) units <- units[keep] tcnSegRow <- range(units) verbose && printf(verbose, "[idxStart,idxEnd] = [%d,%d]\n", tcnSegRow[1], tcnSegRow[2]) verbose && cat(verbose, "Number of TCN loci: ", length(units)) # (c) Adjust for missing values keep <- which(!is.na(CT[units])) units <- units[keep] # (d) Adjust for DH boundaries if (jj > 1L) { minIdx <- tcnSegRowsII[jj-1L,2L, drop=TRUE] units <- units[units > minIdx] } if (jj < J) { maxIdx <- dhSegRowsII[jj+1L,1L, drop=TRUE] units <- units[units < maxIdx] } if (jj == J) { # maxIdx <- dhSegRowsII[jj+1L,1L, drop=TRUE] # units <- units[units < maxIdx] } tcnSegRow <- range(units) verbose && printf(verbose, "[idxStart,idxEnd] = [%d,%d]\n", tcnSegRow[1], tcnSegRow[2]) verbose && cat(verbose, "Number of non-missing TCN loci: ", length(units)) } else { stop("Not implemented yet.") # /HB 2010-12-02 } # if (joinSegments) gamma <- avgTCN(CT[units]) # Sanity check .stop_if_not(length(units) == 0 || !is.na(gamma)) # Update the segment boundaries, estimates and counts seg[["tcnStart"]] <- xStart seg[["tcnEnd"]] <- xEnd seg[["tcnMean"]] <- gamma seg[["tcnNbrOfLoci"]] <- length(units) seg[["tcnNbrOfSNPs"]] <- sum(isSnp[units]) seg[["tcnNbrOfHets"]] <- sum(isHet[units]) # Sanity check .stop_if_not(nrow(seg) == length(jj)) segsII[jj,] <- seg tcnSegRowsII[jj,] <- tcnSegRow verbose && exit(verbose) } # for (jj ...) # Sanity check .stop_if_not(nrow(segsII) == length(rowsII)) verbose && cat(verbose, "TCN & DH segRows afterward:") verbose && print(verbose, cbind(tcn=tcnSegRowsII, dh=dhSegRowsII)) ##print(segsII) # Sanity check nbrOfTCNsAfter <- sum(segsII[,"tcnNbrOfLoci"], na.rm=TRUE) verbose && cat(verbose, "Number of TCNs before: ", nbrOfTCNsBefore) verbose && cat(verbose, "Number of TCNs after: ", nbrOfTCNsAfter) .stop_if_not(nbrOfTCNsAfter >= nbrOfTCNsBefore) # Sanity check .stop_if_not(nrow(dhSegRowsII) == nrow(tcnSegRowsII)) .stop_if_not(all(tcnSegRowsII[,1] <= tcnSegRowsII[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRowsII[-nrow(tcnSegRowsII),2] < tcnSegRowsII[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRowsII[,1] <= dhSegRowsII[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRowsII[-nrow(dhSegRowsII),2] < dhSegRowsII[-1,1], na.rm=TRUE)) segsCC[rowsII,] <- segsII tcnSegRowsCC[rowsII,] <- tcnSegRowsII # Not needed anymore rowsII <- segsII <- NULL verbose && exit(verbose) } # for (ii ...) # Sanity check .stop_if_not(nrow(segsCC) == length(rows)) # Sanity check .stop_if_not(nrow(dhSegRowsCC) == nrow(tcnSegRowsCC)) .stop_if_not(all(tcnSegRowsCC[,1] <= tcnSegRowsCC[,2], na.rm=TRUE)) #################### if (!all(tcnSegRowsCC[-nrow(tcnSegRowsCC),2] < tcnSegRowsCC[-1,1], na.rm=TRUE)) { aa <- tcnSegRowsCC[-nrow(tcnSegRowsCC),2] bb <- tcnSegRowsCC[-1,1] delta <- bb - aa dd <- cbind(aa, bb, delta=delta) print(dd) dd <- subset(dd, delta == 0) print(dd) row <- dd[,1L,drop=TRUE] print(row) rr <- row + -10:10 dd <- data[rr,] rownames(dd) <- rr print(dd) print(tcnSegRowsII) } #################### .stop_if_not(all(tcnSegRowsCC[-nrow(tcnSegRowsCC),2] < tcnSegRowsCC[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRowsCC[,1] <= dhSegRowsCC[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRowsCC[-nrow(dhSegRowsCC),2] < dhSegRowsCC[-1,1], na.rm=TRUE)) segs[rows,] <- segsCC tcnSegRows[rows,] <- tcnSegRowsCC # Not needed anymore rows <- segsCC <- NULL verbose && exit(verbose) } # for (cc ...) # Sanity check .stop_if_not(nrow(dhSegRows) == nrow(tcnSegRows)) .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRows[,1] <= dhSegRows[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRows[-nrow(dhSegRows),2] < dhSegRows[-1,1], na.rm=TRUE)) verbose && enter(verbose, "Update (C1,C2) per segment") # Append (C1,C2) estimates tcn <- segs$tcnMean dh <- segs$dhMean C1 <- 1/2*(1-dh)*tcn C2 <- tcn - C1 segs$c1Mean <- C1 segs$c2Mean <- C2 verbose && exit(verbose) # Return results keep <- which(is.finite(fit$output$chromosome)) fitS <- fit fitS$data <- data fitS$output[keep,] <- segs fitS$tcnSegRows[keep,] <- tcnSegRows # Sanity check tcnSegRows <- fitS$tcnSegRows dhSegRows <- fitS$dhSegRows .stop_if_not(nrow(dhSegRows) == nrow(tcnSegRows)) .stop_if_not(all(tcnSegRows[,1] <= tcnSegRows[,2], na.rm=TRUE)) .stop_if_not(all(tcnSegRows[-nrow(tcnSegRows),2] < tcnSegRows[-1,1], na.rm=TRUE)) .stop_if_not(all(dhSegRows[,1] <= dhSegRows[,2], na.rm=TRUE)) .stop_if_not(all(dhSegRows[-nrow(dhSegRows),2] < dhSegRows[-1,1], na.rm=TRUE)) # Update 'flavor' fitS$params$flavor <- gsub(",", "&", flavor, fixed=TRUE) verbose && exit(verbose) fitS }, protected=TRUE) # postsegmentTCN() PSCBS/R/PSCBS.RESTRUCT.R0000644000176200001440000001040214564051545013602 0ustar liggesuserssetMethodS3("c", "PSCBS", function(..., addSplit = TRUE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - args <- list(...) ## Nothing todo? nargs <- length(args) if (nargs == 1) return(args[[1]]) isNA <- function(x) is.logical(x) && length(x) == 1L && is.na(x) res <- args[[1]] fields <- c("output", "tcnSegRows", "dhSegRows") for (ii in 2:nargs) { arg <- args[[ii]] if (isNA(arg)) { if (addSplit) { warning(sprintf("Detected explicit NA in call to c(<%s>, ..., addSplit = TRUE). Ignoring", class(args[[1]])[1])) next } ## Add "splitter" for (field in fields) { res[[field]] <- rbind(res[[field]], NA) } } else { ## Locus-level data data <- getLocusData(res) data_arg <- getLocusData(arg) if (!all(colnames(data_arg) == colnames(data))) { stop(sprintf("Cannot concatenate %s and %s objects, because they have different sets of columns in field %s: {%s} [n=%d] != {%s} [n=%d]", sQuote(class(res)[1]), sQuote(class(arg)[1]), sQuote(field), paste(sQuote(colnames(data)), collapse=", "), ncol(data), paste(sQuote(colnames(data_arg)), collapse=", "), ncol(data_arg))) } indexOffset <- nrow(data) data <- rbind(data, getLocusData(arg)) res[["data"]] <- data # Segmentation data for (field in fields[-1]) { arg[[field]] <- arg[[field]] + indexOffset } splitter <- if (addSplit) NA else NULL for (field in fields) { res[[field]] <- rbind(res[[field]], splitter, arg[[field]]) } # Known segments ksT <- res$params$knownSegments ksT$length <- NULL # In case it's been added ksO <- arg$params$knownSegments ksO$length <- NULL # In case it's been added res$params$knownSegments <- rbind(ksT, ksO) } } ## for (ii ...) ## Drop row names, iff they've been added for (field in fields) rownames(res[[field]]) <- NULL # Sanity check ns <- sapply(res[fields], FUN = nrow) .stop_if_not(all(ns == ns[1])) res }) # c() setMethodS3("extractChromosomes", "PSCBS", function(x, chromosomes, ...) { # To please R CMD check this <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'chromosomes': disallow <- c("NaN", "Inf") chromosomes <- Arguments$getIntegers(chromosomes, range=c(0,Inf), disallow=disallow) .stop_if_not(all(is.element(chromosomes, getChromosomes(this)))) # Always extract in order chromosomes <- unique(chromosomes) chromosomes <- sort(chromosomes) # Allocate results res <- this # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Locus data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chromosome <- NULL; rm(list="chromosome") # To please R CMD check res$data <- subset(res$data, chromosome %in% chromosomes) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify rows to subset rows <- which(is.element(res$output$chromosome, chromosomes)) for (field in c("output", "tcnSegRows", "dhSegRows")) { res[[field]] <- res[[field]][rows,,drop=FALSE] } # Identify chromosome offsets chrStarts <- match(getChromosomes(this), this$data$chromosome) chrEnds <- c(chrStarts[-1]-1L, nrow(this$data)) chrLengths <- chrEnds - chrStarts + 1L chrLengthsExcl <- chrLengths keep <- match(chromosomes, getChromosomes(this)) chrLengthsExcl[keep] <- 0L cumChrLengthsExcl <- cumsum(chrLengthsExcl) shifts <- cumChrLengthsExcl[keep] .stop_if_not(all(is.finite(shifts))) # Adjust indices for (cc in seq_along(chromosomes)) { chromosome <- chromosomes[cc] shift <- shifts[cc] # Nothing to do? if (shift == 0) next for (field in c("tcnSegRows", "dhSegRows")) { segRows <- res[[field]] rows <- which(res$output$chromosome == chromosome) segRows[rows,] <- segRows[rows,] - shift res[[field]] <- segRows } } res }, protected=TRUE) PSCBS/R/999.NonDocumentedObjects.R0000644000176200001440000000170714564051545016073 0ustar liggesusers###########################################################################/** # @RdocDocumentation "Non-documented objects" # # % Other missing docs # @eval "t <- readLines('../incl/999.missingdocs.txt'); t <- trim(unlist(strsplit(t, split=' '))); t <- t[nchar(t) > 0]; t2 <- gsub('\\[', '\\\\[', t); t <- unique(t); t <- sprintf('\\alias{%s}', t); paste(t, collapse='\n')" # # \description{ # This page contains aliases for all "non-documented" objects that # \code{R CMD check} detects in this package. # # Almost all of them are \emph{generic} functions that have specific # document for the corresponding method coupled to a specific class. # Other functions are re-defined by \code{setMethodS3()} to # \emph{default} methods. Neither of these two classes are non-documented # in reality. # The rest are deprecated methods. # } # # @author # # @keyword internal #*/########################################################################### PSCBS/R/utils.R0000644000176200001440000000067314564051545012627 0ustar liggesusers.stop_if_not <- function(...) { res <- list(...) n <- length(res) if (n == 0L) return() for (ii in 1L:n) { res_ii <- .subset2(res, ii) if (length(res_ii) != 1L || is.na(res_ii) || !res_ii) { mc <- match.call() call <- deparse(mc[[ii + 1]], width.cutoff = 60L) if (length(call) > 1L) call <- paste(call[1L], "...") stop(sQuote(call), " is not TRUE but ", call. = FALSE, domain = NA) } } } PSCBS/R/weightedQuantile.R0000644000176200001440000001274514564051545014775 0ustar liggesusers############################################################################/** # @RdocDefault weightedQuantile # # @title "Weighted Quantile Value" # # @synopsis # # \description{ # Computes a weighted quantile of a numeric vector. # } # # \arguments{ # \item{x}{a @numeric @vector containing the values whose weighted # quantile is to be computed.} # \item{w}{a numeric @vector of weights the same length as # \code{x} giving the weights to use for each element of \code{x}. # Negative weights are treated as zero weights. # Default value is equal weight to all values.} # \item{probs}{a @numeric @vector of quantiles in [0,1] to be retrieved.} # \item{na.rm}{a @logical value indicating whether @NA values in # \code{x} should be stripped before the computation proceeds, # or not.} # \item{method}{If \code{"wtd.quantile"}, then an internal copy of # \code{Hmisc::wtd.quantile()} is used. # No other methods are currently supported.} # \item{...}{Additional arguments passed to the estimator.} # } # # \value{ # Returns the weighted quantile. # } # # @author "HB" # # \seealso{ # Internally the following functions may be used: # @see "stats::quantile" (if no weights are specified), or an internal # copy of \code{Hmisc::wtd.quantile()}. # For a weighted median estimator, @see "matrixStats::weightedMedian" # of the \pkg{matrixStats} package. # } # # @keyword univar # @keyword robust # @keyword internal #*/############################################################################ setMethodS3("weightedQuantile", "default", function(x, w, probs=c(0, 0.25, 0.5, 0.75, 1), na.rm=TRUE, method=c("wtd.quantile"), ...) { # Argument 'x': x <- Arguments$getNumerics(x) # Argument 'w': if (missing(w)) { # By default use weights that are one. w <- rep(1, times=length(x)) } else { w <- Arguments$getNumerics(w, range=c(0,Inf), length=rep(length(x), times=2L)) } naValue <- NA storage.mode(naValue) <- storage.mode(x) # Argument 'na.rm': if (is.na(na.rm)) { # There are no NAs } else if (isTRUE(na.rm)) { # Remove values that are NA's tmp <- !(is.na(x) | is.na(w)) x <- .subset(x, tmp) w <- .subset(w, tmp) } else if (anyNA(x)) { return(naValue) } # Argument 'method': method <- match.arg(method) # Remove values with zero (and negative) weight. This will: # (1) take care of the case when all weights are zero, # (2) it will most likely speed up the sorting. n <- length(w) tmp <- (w > 0) if (!all(tmp)) { x <- .subset(x, tmp) w <- .subset(w, tmp) n <- sum(tmp) } # Are there any values left to calculate the weighted median of? if (n == 0) { return(naValue) } else if (n == 1) { return(x) } # Are any weights Inf? Then treat them with equal weight and all others # with weight zero. If they have equal weight, regular quantile # can be used instead, which is assumed to be faster. tmp <- is.infinite(w) if (any(tmp)) { x <- .subset(x, tmp) # Here we know there are no NAs. return(quantile(x, probs=probs, na.rm=FALSE, ...)) } # Here we know that there are no missing values in the data .wtd.quantile(x, weights=w, probs=probs) }) # weightedQuantile() ## The wtd.quantile() function originates from Hmisc 4.6-0 (2021-10-07), which ## was released under GPL (>= 2). The reasons for copying (and pruning) it ## instead of adding 'Hmisc' as a dependency are several: (i) Hmisc has a large ## number of dependencies, (ii) Hmisc requires R (>= 3.6.0) whereas we try to ## stay backward compatible with R (>= 3.2.0), and, most importantly, (iii) due ## to it's many dependencies Hmisc does not install out of the box on all ## systems, e.g. as of 2021-10-22 it is not available for macOS running on the ## M1 chip. ## ## CHANGES MADE: ## * wtd.quantile(): Dropped argument 'type' - always type="quantile" ## * wtd.quantile(): Dropped argument 'normwt' - always normwt=TRUE ## * wtd.quantile(): Dropped argument 'na.rm' - always na.rm=FALSE .wtd.quantile <- function(x, weights, probs=c(0, .25, .5, .75, 1)) { if(any(probs < 0 | probs > 1)) stop("Probabilities must be between 0 and 1 inclusive") ## NOTE: Data points with zero or NA weights have already been dropped ## by weightedQuantile() before calling this function ## Normalize weights weights <- weights/sum(weights) ## Order (x,weights) by x i <- order(x) x <- x[i] weights <- weights[i] nx <- length(x) ## Merge replicated 'x':s into single ones by combining their weights if (anyDuplicated(x)) { weights <- tapply(weights, INDEX = x, FUN = sum) ## The names of 'weights' holds the unique 'x' values xs <- names(weights) names(weights) <- NULL if (length(xs) == 0) stop("program logic error") x <- as.numeric(xs) } weights <- nx * weights cweights <- cumsum(weights) n <- cweights[length(weights)] order <- 1 + (n - 1) * probs low <- pmax(floor(order), 1) high <- pmin(low + 1, n) order <- order %% 1 ## Find low and high order statistics ## These are minimum values of x such that the cum. freqs >= c(low,high) allq <- approx(cweights, x, xout=c(low,high), method="constant", f=1, rule=2L)$y k <- length(probs) quantiles <- (1 - order)*allq[1:k] + order*allq[-(1:k)] ## Add 'probs' names digits <- if (k > 1) 2 - log10(diff(range(probs))) else 2 names <- paste(format(round(100 * probs, digits = digits)), "%", sep = "") names(quantiles) <- names quantiles } PSCBS/R/AbstractCBS.PLOT.R0000644000176200001440000000232614564051545014334 0ustar liggesusers###########################################################################/** # @set "class=AbstractCBS" # @RdocMethod plotTracks # # @title "Plots the segmentation result along the genome" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{...}{...} # } # # \value{ # Returns nothing. # } # # @author "HB" # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("plotTracks", "AbstractCBS", abstract=TRUE) setMethodS3("tileChromosomes", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("drawChangePoints", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("drawKnownSegments", "AbstractCBS", function(fit, col="#aaaaaa", ..., xScale=1e-6) { segs <- fit$params$knownSegments # Nothing todo? if (is.null(segs)) { return() } # Workaround from the fact that extractChromosomes() does not drop # known segments. /HB 2013-03-21 chromosome <- NULL; rm(list="chromosome") # To please R CMD check. segs <- subset(segs, chromosome %in% getChromosomes(fit)) xStarts <- segs[,"start"] xEnds <- segs[,"end"] xs <- sort(unique(c(xStarts, xEnds))) abline(v=xScale*xs, col=col, ...) }, protected=TRUE) PSCBS/R/AbstractCBS.REPORT.R0000644000176200001440000002056714564051545014600 0ustar liggesusers###########################################################################/** # @set class=AbstractCBS # @RdocMethod report # # @title "Generates a report of the segmentation results" # # \description{ # @get "title". # Currently reports can be generated for segmentation results of class # @see "CBS" and @see "PairedPSCBS". # } # # @synopsis # # \arguments{ # \item{fit}{An @see "AbstractCBS" object.} # \item{sampleName}{A @character string specifying the name of the # sample segmented.} # \item{studyName}{A @character string specifying the name of study/project.} # \item{...}{Optional arguments passed to the RSP template.} # \item{rspTags}{Optional @character @vector of tags for further specifying # which RSP report to generate.} # \item{rootPath}{The root directory where to write the report.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the pathname of the generated PDF. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("report", "AbstractCBS", function(fit, sampleName=getSampleName(fit), studyName, ..., rspTags=NULL, rootPath="reports/", .filename="*", skip=TRUE, envir=new.env(), verbose=FALSE) { use("R.rsp (>= 0.20.0)") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'sampleName': sampleName <- Arguments$getCharacter(sampleName) if (is.na(sampleName)) { stop("Cannot generate report. Argument 'sampleName' is non-valid or missing.") } # Argument 'studyName': if (missing(studyName)) { stop("Cannot generate report. Argument 'studyName' is missing.") } studyName <- Arguments$getCharacter(studyName) if (is.na(studyName)) { stop("Cannot generate report. Argument 'studyName' is non-valid.") } # Argument 'rspTags': if (!is.null(rspTags)) { rspTags <- Arguments$getCharacters(rspTags) rspTags <- unlist(strsplit(rspTags, split=",", fixed=TRUE)) rspTags <- rspTags[nchar(rspTags) > 0L] } # Argument 'rootPath': rootPath <- Arguments$getWritablePath(rootPath) # Argument '.filename': if (!is.null(.filename)) { .filename <- Arguments$getCharacter(.filename, useNames=TRUE) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Generating CBS report") verbose && cat(verbose, "Sample name: ", sampleName) verbose && cat(verbose, "Number of chromosomes: ", nbrOfChromosomes(fit)) verbose && cat(verbose, "Number of segments: ", nbrOfSegments(fit)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Report template arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Default arguments rspArgs <- list( fit = fit, sampleName = sampleName, studyName = studyName, dataSet = NULL, Clim = c(0,2*ploidy(fit)), Blim = c(0,1), figForce = FALSE ) # Override with user arguments userArgs <- list(...) for (key in names(userArgs)) { rspArgs[[key]] <- userArgs[[key]] } if (is.null(rspArgs$reportPath)) { rspArgs$reportPath <- file.path(rootPath, rspArgs$studyName) } rspArgs$reportPath <- Arguments$getWritablePath(rspArgs$reportPath) verbose && cat(verbose, "Report root path: ", rspArgs$reportPath) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Linking to report files # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Linking to report files") # Directory where all report templates lives srcPath <- "templates" # If missing, default to one that comes with PSCBS/templates/ if (!isDirectory(srcPath)) { srcPath <- system.file("templates", package="PSCBS") } srcPath <- file.path(srcPath, "rsp") srcPath <- Arguments$getReadablePath(srcPath) verbose && cat(verbose, "Source path: ", srcPath) filename <- .filename # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Create file links to the main RSP report template # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Main RSP template") # Construct the filename of the main RSP file to compile, iff missing. if (filename == "*") { className <- class(fit)[1] fullname <- paste(c(className, rspTags), collapse=",") filename <- sprintf("%s,report.tex.rsp", fullname) } rspPathname <- file.path(srcPath, filename) verbose && cat(verbose, "RSP report template: ", rspPathname) rspPathname <- Arguments$getReadablePathname(rspPathname) destFilename <- sprintf("%s,%s", sampleName, filename) destPathname <- filePath(rspArgs$reportPath, destFilename) target <- rspPathname link <- destPathname if (!isFile(link)) { verbose && cat(verbose, "Adding link: ", link, " -> ", target) createLink(link=link, target=target) } # Sanity check .stop_if_not(isFile(link)) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Skip? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (skip) { ## Try to guess report filename filename <- basename(destPathname) filename <- gsub("[.]rsp$", "", filename) ext <- gsub(".*[.]", "", filename) fullname <- gsub(sprintf("[.]%s$", ext), "", filename) ext <- switch(ext, tex="pdf", md="html", ext) filename <- sprintf("%s.%s", fullname, ext) pathname <- file.path(rspArgs$reportPath, filename) pathname <- getAbsolutePath(pathname) verbose && cat(verbose, "Expected output pathname: ", pathname) if (isFile(pathname)) { verbose && cat(verbose, "Already exists: Skipping.") report <- R.rsp::RspFileProduct(pathname) return(report) } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Create file links to all LaTeX include files # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "All LaTeX files") files <- list.files(path=srcPath, pattern="[.](bib|bst|cls|sty|tex)$", full.names=TRUE, recursive=FALSE) files <- files[file_test("-f", files)] if (length(files) > 0L) { verbose && cat(verbose, "Number of such files found: ", length(files)) verbose && print(verbose, files) for (kk in seq_along(files)) { target <- files[kk] link <- filePath(rspArgs$reportPath, basename(files[kk])) if (!isFile(link)) { verbose && cat(verbose, "Adding link: ", link, " -> ", target) createLink(link=link, target=target) } # Sanity check .stop_if_not(isFile(link)) } } else { verbose && cat(verbose, "No such files found.") } verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Create file links to all 'incl.*' subdirectories # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "All 'incl.*' subdirectories") dirs <- list.files(srcPath, pattern="^incl", full.names=TRUE, recursive=FALSE) dirs <- dirs[file_test("-d", dirs)] if (length(dirs) > 0L) { verbose && cat(verbose, "Number of such directories found: ", length(dirs)) verbose && print(verbose, dirs) for (kk in seq_along(dirs)) { target <- dirs[kk] link <- filePath(rspArgs$reportPath, basename(dirs[kk])) if (!isDirectory(link)) { verbose && cat(verbose, "Adding link: ", link, " -> ", target) createLink(link=link, target=target) } # Sanity check .stop_if_not(isDirectory(link)) } } else { verbose && cat(verbose, "No such directories found.") } verbose && exit(verbose) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Build reports # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Processing RSP template") rspArgs$figPath <- "figures/" args <- c(list(rspArgs=rspArgs), rspArgs) report <- R.rsp::rfile(destPathname, workdir=rspArgs$reportPath, args=args, envir=envir, verbose=verbose) verbose && exit(verbose) verbose && cat(verbose, "Final report: ", getRelativePath(report)) verbose && exit(verbose) report }, protected=TRUE) PSCBS/R/CBS.PLOT.R0000644000176200001440000003157014564051545012653 0ustar liggesusers###########################################################################/** # @set "class=CBS" # @RdocMethod plotTracks # # @title "Plots copy numbers along the genome" # # \description{ # @get "title" for one or more chromosomes. # Each type of track is plotted in its own panel. # } # # @synopsis # # \arguments{ # \item{x}{A result object returned by @see "segmentByCBS".} # \item{pch}{The type of points to use.} # \item{Clim}{The range of copy numbers.} # \item{xScale}{The scale factor used for genomic positions.} # \item{...}{Not used.} # \item{add}{If @TRUE, the panels plotted are added to the existing plot, # otherwise a new plot is created.} # } # # \value{ # Returns nothing. # } # # @author "HB" # # @keyword IO # @keyword internal #*/########################################################################### setMethodS3("plotTracks", "CBS", function(x, scatter=TRUE, pch=20, col="gray", meanCol="purple", cex=1, grid=FALSE, Clim="auto", xScale=1e-6, Clab="auto", ..., byIndex=FALSE, mar=NULL, add=FALSE) { # To please R CMD check fit <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'add': add <- Arguments$getLogical(add) # Argument 'Clim': if (identical(Clim, "auto")) { signalType <- getSignalType(fit) ploidy <- ploidy(fit) Clim <- switch(signalType, "log2ratio" = c(-2,2) + c(-1,1)*ploidy/2, "ratio" = c(0,3*ploidy), { x_name <- as.character(substitute(x)) warning(sprintf("Setting default 'Clim' assuming the signal type is %s because signalType(%s) is unknown (%s). Use signalType(%s) <- %s to avoid this warning.", sQuote("ratio"), x_name, sQuote(signalType), x_name, sQuote("ratio"))) c(0, 3 * ploidy) } ) ## NOTE: Don't understand why, but with this 'R CMD build' gives: ## "Error: processing vignette 'CBS.tex.rsp' failed with diagnostics: ## Failed to infer argument 'Clim' due to an unknown signalType(): NA" ## /HB 2013-10-14 ## if (!add && is.null(Clim)) { ## stop("Failed to infer argument 'Clim' due to an unknown signalType(): ", signalType) ## } } else if (!add) { Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) } if (identical(Clab, "auto")) { signalType <- getSignalType(fit) Clab <- switch(signalType, "log2ratio" = "log2 CN ratio", "ratio" = "CN ratio", NULL ) } # Argument 'fit': if (nbrOfChromosomes(fit) > 1L) { res <- plotTracksManyChromosomes(fit, scatter=scatter, pch=pch, col=col, cex=cex, meanCol=meanCol, Clim=Clim, xScale=xScale, Clab=Clab, ..., byIndex=byIndex, mar=mar, add=add) return(invisible(res)) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Extract the input data data <- getLocusData(fit) if (is.null(data)) { stop("Cannot plot segmentation results. No input data available.") } chromosomes <- getChromosomes(fit) chromosome <- chromosomes[1] x <- data$x CT <- data[,3] nbrOfLoci <- length(x) # Extract the segmentation segs <- getSegments(fit) if (chromosome != 0) { chrTag <- sprintf("Chr%02d", chromosome) } else { chrTag <- "" } if (xScale != 1) { x <- xScale * x } if (!add && !is.null(mar)) { par(mar=mar) } pchT <- if (scatter) { pch } else { NA } plot(x, CT, pch=pchT, cex=cex, col=col, ..., ylim=Clim, ylab=Clab) stext(side=3, pos=1, chrTag) if (grid) { yrange <- par("usr")[3:4] yrange[1] <- floor(yrange[1]) yrange[2] <- ceiling(yrange[2]) abline(h=seq(from=yrange[1], to=yrange[2], by=2), lty=3, col="gray") abline(h=0, lty=1, col="black") } drawLevels(fit, col=meanCol, xScale=xScale) invisible() }) # plotTracks() setMethodS3("plot", "CBS", function(x, ...) { plotTracks(x, ...) }, protected=TRUE) setMethodS3("drawLevels", "CBS", function(fit, col="purple", xScale=1e-6, byIndex=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # Get segmentation results segs <- as.data.frame(fitT) # Extract subset of segments fields <- c("start", "end", "mean") segs <- segs[,fields, drop=FALSE] segs <- unique(segs) # Reuse drawLevels() for the DNAcopy class colnames(segs) <- c("loc.start", "loc.end", "seg.mean") dummy <- list(output=segs) class(dummy) <- "DNAcopy" drawLevels(dummy, col=col, xScale=xScale, ...) }, protected=TRUE) setMethodS3("highlightCalls", "CBS", function(fit, pch=20, callCols=c(loss="red", gain="green", "amplification"="blue"), lwd=3, meanCol="purple", ..., xScale=1e-6, byIndex=FALSE, verbose=FALSE) { segs <- getSegments(fit, splitter=FALSE) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify segment calls # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - callFields <- grep("Call$", colnames(segs)) callTypes <- gsub("Call$", "", colnames(segs)[callFields]) nbrOfCalls <- length(callFields) # Nothing todo? if (nbrOfCalls == 0L) { return() } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Highlight threshold levels # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - params <- fit$params$callGainsAndLosses abline(h=params$muR, col="gray", lty=3) abline(h=params$tauLoss, col=callCols["loss"], lty=3) abline(h=params$tauGain, col=callCols["gain"], lty=3) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Highlight gains and losses # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - dataT <- getLocusData(fitT) segsT <- getSegments(fitT, splitter=FALSE) chr <- dataT[,"chromosome"] x <- dataT[,"x"] y <- dataT[,3] nbrOfLoci <- nbrOfLoci(fitT) nbrOfSegments <- nbrOfSegments(fitT) # Not needed anymore dataT <- NULL # For each non-neutral segment for (ss in seq_len(nbrOfSegments)) { seg <- segsT[ss,] for (tt in seq_along(callTypes)) { field <- callFields[tt] type <- callTypes[tt] # Called? call <- seg[[field]] if (isTRUE(call)) { col <- callCols[type] idxs <- which(chr == seg$chromosome & seg$start <= x & x <= seg$end) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) if (byIndex) { xs <- idxs } else { xs <- x[idxs] * xScale } ys <- y[idxs] points(xs, ys, pch=pch, col=col, ...) xx <- range(xs, na.rm=TRUE) yy <- rep(seg$mean, times=2) lines(xx, yy, lwd=lwd, col=meanCol) } } # for (tt ...) } # for (ss ...) }, protected=TRUE) # highlightCalls() setMethodS3("highlightLocusCalls", "CBS", function(fit, callPchs=c(negOutlier=25, posOutlier=24), callCols=c(negOutlier="blue", posOutlier="blue"), ..., xScale=1e-6, byIndex=FALSE, verbose=FALSE) { data <- getLocusData(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify segment calls # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - callFields <- grep("Call$", colnames(data)) callTypes <- gsub("Call$", "", colnames(data)[callFields]) nbrOfCalls <- length(callFields) # Nothing todo? if (nbrOfCalls == 0) { return() } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Highlight gains and losses # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - dataT <- getLocusData(fitT) chr <- dataT[,"chromosome"] x <- dataT[,"x"] y <- dataT[,3] nbrOfLoci <- nbrOfLoci(fitT) # For each non-neutral segment for (tt in seq_along(callTypes)) { field <- callFields[tt] type <- callTypes[tt] isCalled <- dataT[[field]] idxs <- which(isCalled) if (length(idxs) == 0L) { next } if (byIndex) { xs <- idxs } else { xs <- x[idxs] * xScale } ys <- y[idxs] pch <- callPchs[type] col <- callCols[type] points(xs, ys, pch=pch, col=col, ...) } # for (tt ...) }, protected=TRUE) # highlightLocusCalls() setMethodS3("drawChromosomes", "CBS", function(x, lty=3, xScale=1e-6, ..., byIndex=FALSE, verbose=FALSE) { # To please R CMD check fit <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # Sanity check .stop_if_not(!is.null(fitT$chromosomeStats)) chrStats <- fitT$chromosomeStats chrStats <- chrStats[-nrow(chrStats),,drop=FALSE] chrRanges <- as.matrix(chrStats[,c("start","end")]) vs <- xScale * chrRanges mids <- (vs[,1]+vs[,2])/2 chromosomes <- getChromosomes(fitT) chrLabels <- sprintf("%02d", chromosomes) side <- rep(c(1,3), length.out=length(chrLabels)) mtext(text=chrLabels, side=side, at=mids, line=0.1, cex=0.7*par("cex")) abline(v=vs, lty=lty) }, protected=TRUE) # drawChromosomes() setMethodS3("drawCentromeres", "CBS", function(fit, genomeData, what=c("start", "end"), xScale=1e-6, col="gray", lty=3, ..., byIndex=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'genomeData': .stop_if_not(inherits(genomeData, "data.frame")) .stop_if_not(is.element("chromosome", colnames(genomeData))) .stop_if_not(is.element("centroStart", colnames(genomeData))) .stop_if_not(is.element("centroEnd", colnames(genomeData))) # Calculate the midpoints of the centromeres colnames(genomeData) <- tolower(gsub("centro", "", colnames(genomeData))) genomeData$mid <- (genomeData$start + genomeData$end) / 2 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) # Sanity check .stop_if_not(!is.null(fitT$chromosomeStats)) chrStats <- fitT$chromosomeStats offsets <- chrStats[,"start"] - chrStats[1,"start"] # Centroid locations in the tiled space offsetsT <- offsets[seq_len(nrow(genomeData))] xx <- genomeData[,what,drop=FALSE] xx <- as.matrix(xx) xx <- offsetsT + xx ats <- xScale * xx for (cc in seq_len(ncol(xx))) { abline(v=ats[,cc], col=col, lty=lty, ...) } invisible(ats) }, protected=TRUE) # drawCentromeres() setMethodS3("highlightArmCalls", "CBS", function(fit, genomeData, minFraction=0.95, callCols=c("loss"="red", "gain"="green"), xScale=1e-6, ...) { # To please/trick R CMD check chromosome <- x <- NULL; rm(list=c("chromosome", "x")) callStats <- callArms(fit, genomeData=genomeData, minFraction=minFraction) callTypes <- grep("Fraction", colnames(callStats), value=TRUE) callTypes <- gsub("Fraction", "", callTypes) callTypes <- intersect(callTypes, c("loss", "gain")) # Adjust (start, end) offsets <- getChromosomeOffsets(fit) offsets <- offsets[callStats[,"chromosome"]] callStats[,c("start","end")] <- offsets + callStats[,c("start","end")] nbrOfRegions <- nrow(callStats) # Nothing todo? if (nbrOfRegions == 0) { return(invisible(callStats)) } usr <- par("usr") dy <- diff(usr[3:4]) yy <- usr[3]+c(0,0.05*dy) abline(h=usr[3]+0.95*0.05*dy, lty=1, col="gray") xx <- callStats[,c("start", "end")] xx <- as.matrix(xx) xx <- xx * xScale for (type in callTypes) { col <- callCols[type] keyA <- sprintf("%sFraction", type) keyB <- sprintf("%sCall", type) for (kk in seq_len(nbrOfRegions)) { xs <- xx[kk,] score <- callStats[kk, keyA] if (is.finite(score) && score > 0) { ys <- rep(yy[1]+callStats[kk, keyA]*0.05*dy, times=2) lines(x=xs, y=ys, col=col) call <- callStats[kk, keyB] if (call) { rect(xs[1], yy[1], xs[2], yy[2], col=col, border=NA) } } } } # for (type ...) invisible(callStats) }, protected=TRUE) # highlightArmCalls() PSCBS/R/NonPairedPSCBS.R0000644000176200001440000002613014564051545014135 0ustar liggesusers###########################################################################/** # @RdocClass NonPairedPSCBS # # @title "The NonPairedPSCBS class" # # \description{ # @classhierarchy # # A NonPairedPSCBS is an object containing the results from the # Non-paired PSCBS method. # } # # \usage{NonPairedPSCBS(fit=list(), ...)} # # \arguments{ # \item{fit}{A @list structure containing the Non-paired PSCBS results.} # \item{...}{Not used.} # } # # \section{Fields and Methods}{ # @allmethods "public" # } # # @author "HB" # # \seealso{ # The @see "segmentByNonPairedPSCBS" method returns an object of this class. # } #*/########################################################################### setConstructorS3("NonPairedPSCBS", function(fit=list(), ...) { # Argument 'fit': if (!is.list(fit)) { stop("Argument 'fit' is not a list: ", class(fit)[1]) } extend(PSCBS(fit=fit, ...), "NonPairedPSCBS") }) setMethodS3("getLocusData", "NonPairedPSCBS", function(fit, ..., fields=c("asis", "full")) { # Argument 'fields': fields <- match.arg(fields) data <- NextMethod("getLocusData", fields="asis") if (fields == "full") { names <- colnames(data) data$isHet <- (data$muN == 1/2) # BACKWARD COMPATIBILITY: If 'rho' does not exists, calculate # it on the fly from 'betaT'. # NOTE: This should give an error in the future. /HB 2013-10-25 if (is.null(data$rho)) { data$rho <- 2*abs(data$betaT-1/2) data$rho[!data$isHet] <- NA_real_ warning("Locus-level DH signals ('rho') did not exist and were calculated from tumor BAFs ('betaT')") } data$c1 <- 1/2*(1-data$rho)*data$CT data$c2 <- data$CT - data$c1 data$isSNP <- (!is.na(data$betaT) | !is.na(data$muN)) data$type <- ifelse(data$isSNP, "SNP", "non-polymorphic locus") # Labels data$muNx <- c("AA", "AB", "BB")[2*data$muN + 1L] data$isHetx <- c("AA|BB", "AB")[data$isHet + 1L] } data }, protected=TRUE) # getLocusData() setMethodS3("callROH", "NonPairedPSCBS", function(fit, ...) { stop(sprintf("Cannot call ROH from '%s' data.", class(fit)[1L])) }, private=TRUE) # callROH() setMethodS3("updateMeans", "NonPairedPSCBS", function(fit, from=c("loci", "segments"), adjustFor=NULL, ..., avgTCN=c("asis", "mean", "median"), avgDH=c("asis", "mean", "median"), verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'from': from <- match.arg(from) # Argument 'adjustFor': if (!is.null(adjustFor)) { adjustFor <- Arguments$getCharacters(adjustFor) adjustFor <- tolower(adjustFor) knownValues <- c("ab", "loh", "roh") adjustFor <- match.arg(adjustFor, choices=knownValues, several.ok=TRUE) } # Argument 'avgTCN' & 'avgDH': avgTCN <- match.arg(avgTCN) avgDH <- match.arg(avgDH) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Updating mean level estimates") verbose && cat(verbose, "Adjusting for:") verbose && print(verbose, adjustFor) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up averaging functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (avgTCN == "asis" || avgDH == "asis") { est <- fit$params$meanEstimators if (avgTCN == "asis") { avgTCN <- est$tcn if (is.null(avgTCN)) avgTCN <- "mean" avgTCN <- match.arg(avgTCN) } if (avgDH == "asis") { avgDH <- est$dh if (is.null(avgDH)) avgDH <- "mean" avgDH <- match.arg(avgDH) } } avgList <- list( tcn = get(avgTCN, mode="function"), dh = get(avgDH, mode="function") ) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract the segmentation results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- getSegments(fit, splitters=TRUE) segRows <- list(tcn=fit$tcnSegRows, dh=fit$dhSegRows) nbrOfSegments <- nrow(segs) verbose && cat(verbose, "Number of segments: ", nbrOfSegments) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Assert that adjustments can be made # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.element("ab", adjustFor)) { if (!is.element("abCall", names(segs))) { adjustFor <- setdiff(adjustFor, "ab") stop("Cannot adjust for AB, because they haven't been called.") } } if (is.element("loh", adjustFor)) { if (!is.element("lohCall", names(segs))) { adjustFor <- setdiff(adjustFor, "loh") stop("Cannot adjust for LOH, because they haven't been called.") } } if (is.element("roh", adjustFor)) { if (!is.element("rohCall", names(segs))) { adjustFor <- setdiff(adjustFor, "roh") stop("Cannot adjust for ROH, because they haven't been called.") } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update the (TCN,DH) mean levels from locus-level data? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (from == "loci") { data <- getLocusData(fit) chromosome <- data$chromosome x <- data$x CT <- data$CT rho <- data$rho isSplitter <- isSegmentSplitter(fit) for (ss in seq_len(nbrOfSegments)[!isSplitter]) { verbose && enter(verbose, sprintf("Segment %d of %d", ss, nbrOfSegments)) seg <- segs[ss,] verbose && print(verbose, seg) chr <- seg[["chromosome"]] chrTag <- sprintf("chr%02d", chr) for (what in c("tcn", "dh")) { segRow <- segRows[[what]][ss,] # (a) A splitter - nothing todo? if (!is.finite(segRow[[1]]) || !is.finite(segRow[[2]])) { next } # (b) Identify units (loci) units <- segRow[[1]]:segRow[[2]] # (c) Adjust for missing values if (what == "tcn") { value <- CT } else if (what == "dh") { value <- rho } keep <- which(!is.na(value[units])) units <- units[keep] # (d) Update mean avgFUN <- avgList[[what]] gamma <- avgFUN(value[units]) # Sanity check .stop_if_not(length(units) == 0 || !is.na(gamma)) # Update the segment boundaries, estimates and counts key <- paste(what, "Mean", sep="") seg[[key]] <- gamma } verbose && print(verbose, seg) segs[ss,] <- seg verbose && exit(verbose) } # for (ss ...) } # if (from ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Adjust segment means from various types of calls # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (length(adjustFor) > 0) { verbose && enter(verbose, "Adjusting segment means") verbose && cat(verbose, "Adjusting for:") verbose && print(verbose, adjustFor) if (is.element("ab", adjustFor)) { verbose && enter(verbose, "Adjusting for AB") calls <- segs$abCall segs$dhMean[calls] <- 1/2 verbose && exit(verbose) } if (is.element("loh", adjustFor)) { verbose && enter(verbose, "Adjusting for LOH") calls <- segs$lohCall segs$dhMean[calls] <- 0 verbose && exit(verbose) } if (is.element("roh", adjustFor)) { verbose && enter(verbose, "Adjusting for ROH") calls <- segs$rohCall segs$dhMean[calls] <- NA_real_ verbose && exit(verbose) } verbose && exit(verbose) } # if (length(adjustFor) > 0) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update (C1,C2) mean levels # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update (C1,C2) per segment") # Append (C1,C2) estimates tcn <- segs$tcnMean dh <- segs$dhMean C1 <- 1/2*(1-dh)*tcn C2 <- tcn - C1 segs$c1Mean <- C1 segs$c2Mean <- C2 verbose && exit(verbose) # Return results res <- fit res$output <- segs res <- setMeanEstimators(res, tcn=avgTCN, dh=avgDH) verbose && exit(verbose) res }, private=TRUE) # updateMeans() setMethodS3("resegment", "NonPairedPSCBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Resegmenting a ", class(fit)[1], " object") # Use the locus-level data of the PairedPSCBS object data <- getLocusData(fit) class(data) <- "data.frame" drop <- c("rho", "betaTN", "index") keep <- !is.element(colnames(data), drop) data <- data[,keep] verbose && str(verbose, data) verbose && cat(verbose, "Number of loci: ", nrow(data)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup arguments to be passed # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Overriding default arguments") segFcnName <- "segmentByPairedNonPSCBS" segFcn <- getMethodS3(segFcnName, "default") # (a) The default arguments formals <- formals(segFcn) formals <- formals[!sapply(formals, FUN=is.language)] formals <- formals[!sapply(formals, FUN=is.name)] drop <- c("chromosome", "x", "w", "CT", "betaT", "betaN", "muN", "...") keep <- !is.element(names(formals), drop) formals <- formals[keep] # (b) The arguments used in previous fit params <- fit$params keep <- is.element(names(params), names(formals)) params <- params[keep] # Don't trust 'tbn'! TODO. /HB 20111117 params$tbn <- NULL # (c) The arguments in '...' userArgs <- list(..., verbose=verbose) # (d) Merge args <- formals args2 <- c(params, userArgs) for (kk in seq_along(args2)) { value <- args2[[kk]] if (!is.null(value)) { key <- names(args2)[kk] if (!is.null(key)) { args[[key]] <- value } else { args <- c(args, list(value)) } } } # for (key ...) verbose && str(verbose, args[names(args) != "verbose"]) verbose && enter(verbose, sprintf("Calling %s()", segFcnName)) args <- c(list(data), args) verbose && cat(verbose, "Arguments:") verbose && str(verbose, args[names(args) != "verbose"]) verbose && exit(verbose) fit <- do.call(segFcnName, args) verbose && exit(verbose) verbose && exit(verbose) fit }, protected=TRUE) # resegment() ############################################################################## # HISTORY # 2013-04-23 # o BUG FIX: updateMeans() for PairedPSCBS and NonPairedPSCBS could # include a signal from a neighboring segment when averaging, iff # that signal was located at the exact locus of the change point. # 2013-04-09 # o Added callROH() for NonPairedPSCBS that throws an exception. # 2013-03-08 # o Added getLocusData() for NonPairedPSCBS. # 2013-01-15 # o regsegment() was defined for PairedPSCBS instead of NonPairedPSCBS. # 2012-04-21 # o Created from PairedPSCBS.R. ############################################################################## PSCBS/R/callSegmentationOutliers.R0000644000176200001440000001542214564051545016505 0ustar liggesusers###########################################################################/** # @RdocGeneric callSegmentationOutliers # @alias callSegmentationOutliers.default # @alias callSegmentationOutliers.data.frame # @alias dropSegmentationOutliers # @alias dropSegmentationOutliers.default # @alias dropSegmentationOutliers.data.frame # # @title "Calls/drops single-locus outliers along the genome" # # \description{ # @get "title" that have a signal that differ significantly from the # neighboring loci. # } # # \usage{ # @usage callSegmentationOutliers,default # @usage callSegmentationOutliers,data.frame # @usage dropSegmentationOutliers,default # @usage dropSegmentationOutliers,data.frame # } # # \arguments{ # \item{y}{A @numeric @vector of J genomic signals to be segmented.} # \item{chromosome}{(Optional) An @integer scalar # (or a @vector of length J contain a unique value). # Only used for annotation purposes.} # \item{x}{Optional @numeric @vector of J genomic locations. # If @NULL, index locations \code{1:J} are used.} # \item{method}{A @character string specifying the method # used for calling outliers.} # \item{...}{Additional arguments passed to internal outlier # detection method.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # \code{callSegmentationOutliers()} returns a @logical @vector of length J. # \code{dropSegmentationOutliers()} returns an object of the same type # as argument \code{y}, where the signals for which outliers were called # have been set to @NA. # } # # \section{Missing and non-finite values}{ # Signals as well as genomic positions may contain missing # values, i.e. @NAs or @NaNs. By definition, these cannot # be outliers. # } # # @author "HB" # # \seealso{ # Internally @see "DNAcopy::smooth.CNA" is utilized to identify # the outliers. # } # # @keyword IO #*/########################################################################### setMethodS3("callSegmentationOutliers", "default", function(y, chromosome=0, x=NULL, method="DNAcopy::smooth.CNA", ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'y': disallow <- c("Inf") y <- Arguments$getDoubles(y, disallow=disallow) nbrOfLoci <- length(y) length2 <- rep(nbrOfLoci, times=2L) # Argument 'chromosome': disallow <- c("NaN", "Inf") chromosome <- Arguments$getIntegers(chromosome, range=c(0,Inf), disallow=disallow) if (length(chromosome) == 1L) { chromosome <- rep(chromosome, times=nbrOfLoci) } else { chromosome <- Arguments$getVector(chromosome, length=length2) } # Argument 'x': if (!is.null(x)) { disallow <- c("Inf") x <- Arguments$getDoubles(x, length=length2, disallow=disallow) } # Argument 'method': method <- match.arg(method) verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Identifying outliers") uChromosomes <- sort(unique(chromosome)) nbrOfChromosomes <- length(uChromosomes) verbose && cat(verbose, "Number of chromosomes: ", nbrOfChromosomes) verbose && cat(verbose, "Number of loci: ", nbrOfLoci) verbose && cat(verbose, "Detection method: ", method) # Allocate result vector isOutlier <- logical(nbrOfLoci) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Filter missing data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identifying loci with non-missing data") keep <- (!is.na(x) & !is.na(y)) if (!is.null(chromosome)) { keep <- (keep & !is.na(chromosome)) } keep <- which(keep) chromosome <- chromosome[keep] x <- x[keep] y <- y[keep] nbrOfLoci <- length(x) verbose && cat(verbose, "Number of loci with non-missing data: ", nbrOfLoci) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each chromosome # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - isOutlierT <- logical(nbrOfLoci) for (kk in seq_along(uChromosomes)) { chr <- uChromosomes[kk] verbose && enter(verbose, sprintf("Chromosome #%d ('Chr%02d') of %d", kk, chr, length(uChromosomes))) keepKK <- which(chromosome == chr) nbrOfLociKK <- length(keepKK) verbose && cat(verbose, "Number of loci on chromosome: ", nbrOfLociKK) # Extract data yKK <- y[keepKK] xKK <- x[keepKK] chromosomeKK <- chromosome[keepKK] # Order loci along chromosome o <- order(xKK) xKK <- xKK[o] yKK <- yKK[o] chromosomeKK <- chromosomeKK[o] keepKK <- keepKK[o] o <- NULL # Not needed anymore # Supress all warnings, in order to avoid warnings by DNAcopy::CNA() # on "array has repeated maploc positions". Ideally we should filter # just those out. /HB 2013-10-22 suppressWarnings({ dataKK <- CNA(genomdat=yKK, chrom=chromosomeKK, maploc=xKK, sampleid="y", presorted=TRUE) }) chromosomeKK <- xKK <- NULL # Not needed anymore yKKs <- smooth.CNA(dataKK, ...)$y dataKK <- NULL # Not needed anymore # Sanity check .stop_if_not(length(yKKs) == nbrOfLociKK) outliersKK <- which(yKKs != yKK) yKKs <- yKK <- NULL # Not needed anymore nbrOfOutliers <- length(outliersKK) verbose && cat(verbose, "Number of outliers: ", nbrOfOutliers) outliers <- keepKK[outliersKK] keepKK <- outliersKK <- NULL # Not needed anymore isOutlierT[outliers] <- TRUE outliers <- NULL # Not needed anymore verbose && exit(verbose) } # for (kk ...) chromosome <- x <- y <- NULL # Not needed anymore isOutlier[keep] <- isOutlierT isOutlierT <- keep <- NULL # Not needed anymore nbrOfOutliers <- sum(isOutlier, na.rm=TRUE) verbose && cat(verbose, "Total number of outliers: ", nbrOfOutliers) verbose && exit(verbose) isOutlier }) # callSegmentationOutliers() setMethodS3("callSegmentationOutliers", "data.frame", function(y, ...) { data <- y # Get either CBS or PSCBS total CN signals. y <- data$y if (is.null(y)) { y <- data$CT } callSegmentationOutliers(y=y, chromosome=data$chromosome, x=data$x, ...) }) # callSegmentationOutliers() setMethodS3("dropSegmentationOutliers", "default", function(y, ...) { isOutlier <- callSegmentationOutliers(y, ...) y[isOutlier] <- NA_real_ isOutlier <- NULL # Not needed anymore y }) setMethodS3("dropSegmentationOutliers", "data.frame", function(y, ...) { data <- y isOutlier <- callSegmentationOutliers(data, ...) # Update either CBS or PSCBS total CN signals. key <- "CT" if (!is.element(key, colnames(data))) { key <- "y" } data[[key]][isOutlier] <- NA_real_ isOutlier <- NULL # Not needed anymore data }) PSCBS/R/PairedPSCBS.BOOT.sets.R0000644000176200001440000004134614564051545015207 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod getBootstrapLocusSets # @alias getBootstrapLocusSets # # @title "Generates original and bootstrapped segment-specific index sets" # # \description{ # @get "title", which can be used to calculate various bootstrap summaries, # e.g. segment mean levels. # } # # @synopsis # # \arguments{ # \item{B}{A non-negative @integer specifying the number of bootstrap samples.} # \item{by}{Should \code{betaTN} or \code{betaT} be used?} # \item{seed}{An (optional) @integer specifying the random seed to be # set before sampling indices. The random seed is set to its original # state when exiting. If @NULL, it is not set.} # \item{verbose}{See @see "R.utils::Verbose".} # \item{.validate}{If @TRUE, additional sanity checks are performed # to validate the correctness. This is only needed for troubleshooting # if it is suspected there is a bug.} # \item{...}{Not used.} # } # # \value{ # Returns a @list. # } # # @author "HB" # # \seealso{ # This is used internally by various bootstrap methods. # } # # @keyword internal #*/########################################################################### setMethodS3("getBootstrapLocusSets", "PairedPSCBS", function(fit, B=1000L, by=c("betaTN", "betaT"), seed=NULL, verbose=FALSE, .validate=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'B': B <- Arguments$getInteger(B, range=c(0,Inf)) # Argument 'by': by <- match.arg(by) # Argument 'seed': if (!is.null(seed)) { seed <- Arguments$getInteger(seed) } # Argument '.validate': .validate <- Arguments$getLogical(.validate) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Bootstrapping (TCN,DH,C1,C2) segment mean levels") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Set the random seed # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=%d)\n", seed) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) tcnSegRows <- fit$tcnSegRows dhSegRows <- fit$dhSegRows segs <- getSegments(fit) params <- fit$params # Sanity checks if (!params$joinSegments) { stop("Cannot bootstrap TCN and DH by segments unless PSCNs are segmented using joinSegments=TRUE.") } if (regexpr(",", params$flavor, fixed=TRUE) != -1L) { stop(sprintf("Cannot bootstrap TCN and DH by segments if PSCNs are segmented using flavor=\"%s\".", params$flavor)) } # Sanity check (same as above, but just in case) .stop_if_not(all(segs$tcnStart == segs$dhStart, na.rm=TRUE)) .stop_if_not(all(segs$tcnEnd == segs$dhEnd, na.rm=TRUE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get signals # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get (x,TCN,BAF) data chromosome <- data$chromosome x <- data$x CT <- data$CT betaT <- data[[by]] muN <- data$muN rho <- data$rho hasDH <- !is.null(rho) # Not needed anymore data <- NULL # Sanity checks .stop_if_not(all(!is.na(chromosome) & !is.na(x))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Classify each locus as (i) heterozygous SNP, (ii) homozygous SNP, # or (iii) non-polymorphic loci # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identifying heterozygous & homozygous SNPs and non-polymorphic loci") nbrOfLoci <- length(x) verbose && cat(verbose, "Number of loci: ", nbrOfLoci) # SNPs are identifies as those loci that have non-missing 'muN' (& betaTN') if (hasDH) { isHet <- !is.na(rho) isSnp <- isHet } else { isSnp <- (!is.na(muN) & !is.na(betaT)) isHet <- isSnp & (muN == 1/2) } snps <- which(isSnp) nonSNPs <- which(!isSnp) nbrOfSNPs <- sum(isSnp) nbrOfNonSNPs <- sum(!isSnp) verbose && cat(verbose, "Number of SNPs: ", nbrOfSNPs) verbose && cat(verbose, "Number of non-SNPs: ", nbrOfNonSNPs) # Sanity checks .stop_if_not(length(intersect(snps, nonSNPs)) == 0L) # Heterozygous SNPs hets <- which(isSnp & isHet) homs <- which(isSnp & !isHet) nbrOfHets <- length(hets) nbrOfHoms <- length(homs) if (!hasDH) { verbose && printf(verbose, "Number of heterozygous SNPs: %d (%.2f%%)\n", nbrOfHets, 100*nbrOfHets/nbrOfSNPs) verbose && printf(verbose, "Number of homozygous SNPs: %d (%.2f%%)\n", nbrOfHoms, 100*nbrOfHoms/nbrOfSNPs) } # Sanity checks .stop_if_not(length(intersect(hets, homs)) == 0L) .stop_if_not(nbrOfHets + nbrOfHoms == nbrOfSNPs) # Sanity checks .stop_if_not(length(isSnp) == nbrOfLoci) .stop_if_not(length(isHet) == nbrOfLoci) # Not needed anymore muN <- isSnp <- NULL verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Precalculate DH signals # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!hasDH) { # Calculate DHs for heterozygous SNPs rho <- 2*abs(betaT - 1/2) # DH is by definition only defined for heterozygous SNPs. # For simplicity, we set it to be NA for non-heterozygous loci. rho[!isHet] <- NA } # Not needed anymore betaT <- isHet <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Resample (TCN,DH) within each segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nrow(segs) # Allocate JxBx4 matrix M of bootstrap means dim <- c(nbrOfSegments, B, 4L) dimnames <- list(NULL, NULL, c("tcn", "dh", "c1", "c2")) # Identify all loci with non-missing signals idxsCT <- which(!is.na(CT)) idxsRho <- which(!is.na(rho)) # Not needed anymore CT <- rho <- NULL # Vectorized pre-adjustments for (key in c("tcnNbrOfLoci", "dhNbrOfLoci")) { counts <- segs[[key]] counts[is.na(counts)] <- 0L segs[[key]] <- counts counts <- NULL # Not needed anymore } hasTcnLoci <- (is.finite(tcnSegRows[,1L]) & is.finite(tcnSegRows[,2L])) hasDhLoci <- (is.finite(dhSegRows[,1L]) & is.finite(dhSegRows[,2L])) # Identify "splitter" segments which have no data chrs <- segs[["chromosome"]] tcnIds <- segs[["tcnId"]] dhIds <- segs[["dhId"]] dhMeans <- segs[["dhMean"]] isSplitter <- (is.na(chrs) & is.na(tcnIds) & is.na(dhIds)) # Get all segment indices except for "splitters" jjs <- seq_len(nbrOfSegments) jjs <- jjs[!isSplitter] # Allocate list to hold the results res <- list( nbrOfSegments = nbrOfSegments, segments = jjs, nbrOfLoci = nbrOfLoci, loci = list( all = seq_len(nbrOfLoci), tcn = idxsCT, dh = idxsRho ), by = by, seed = seed ) locusSet <- vector("list", length=nbrOfSegments) # For each segment jj = 1, 2, ..., S for (jj in jjs) { chr <- chrs[jj] tcnId <- tcnIds[jj] dhId <- dhIds[jj] verbose && enter(verbose, sprintf("Segment #%d (chr %d, tcnId=%d, dhId=%d) of %d", jj, chr, tcnId, dhId, nbrOfSegments)) # Sanity check if (.validate) { .stop_if_not(!is.na(chr) && !is.na(tcnId) && !is.na(dhId)) } # Get the segment data segJJ <- segs[jj,,drop=FALSE] nbrOfTCNs <- segJJ[,"tcnNbrOfLoci"] nbrOfDHs <- segJJ[,"dhNbrOfLoci"] if (verbose) { print(verbose, segJJ) cat(verbose, "Number of TCNs: ", nbrOfTCNs) cat(verbose, "Number of DHs: ", nbrOfDHs) } if (.validate) { .stop_if_not(!is.na(nbrOfTCNs)) .stop_if_not(!is.na(nbrOfDHs)) } tcnSegRowJJ <- unlist(tcnSegRows[jj,], use.names=FALSE) dhSegRowJJ <- unlist(dhSegRows[jj,], use.names=FALSE) # Indices of all loci if (hasTcnLoci[jj]) { idxsAll <- tcnSegRowJJ[1L]:tcnSegRowJJ[2L] } else { idxsAll <- integer(0L) } if (verbose) { str(verbose, idxsAll) print(verbose, hpaste(idxsAll), level=-120) str(verbose, idxsCT) print(verbose, hpaste(idxsCT), level=-120) } # Keep only loci with finite TCNs idxsAll <- intersect(idxsAll, idxsCT) if (verbose) { str(verbose, idxsAll) print(verbose, hpaste(idxsAll), level=-120) } # Sanity check if (length(idxsAll) != nbrOfTCNs) { verbose && str(verbose, setdiff(idxsCT, idxsAll)) stop("INTERNAL ERROR: length(idxsAll) != nbrOfTCNs: ", length(idxsAll), " != ", nbrOfTCNs) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify loci used to calculate DH means # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identify loci used to bootstrap DH means") if (hasDhLoci[jj]) { idxsDH <- dhSegRowJJ[1L]:dhSegRowJJ[2L] idxsDH <- intersect(idxsDH, hets) # Drop missing values idxsDH <- intersect(idxsDH, idxsRho) } else { idxsDH <- integer(0L) } verbose && cat(verbose, "Heterozygous SNPs to resample for DH:") verbose && str(verbose, idxsDH) # Sanity check if (.validate) .stop_if_not(length(idxsDH) == nbrOfDHs) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify loci used to calculate TCN means # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identify loci used to bootstrap TCN means") # Identify SNPs and non-SNPs idxsSNP <- intersect(snps, idxsAll) idxsNonSNP <- setdiff(idxsAll, idxsSNP) if (verbose) { cat(verbose, "SNPs:") str(verbose, idxsSNP) cat(verbose, "Non-polymorphic loci:") str(verbose, idxsNonSNP) } # Sanity check if (.validate) .stop_if_not(length(idxsSNP) + length(idxsNonSNP) == length(idxsAll)) # Identify heterozygous and homozygous SNPs idxsHet <- intersect(idxsSNP, hets) if (nbrOfHoms > 0) { idxsHom <- intersect(idxsSNP, homs) } else { idxsHom <- integer(0L) } # Drop missing values idxsNonSNP <- intersect(idxsNonSNP, idxsCT) idxsHet <- intersect(idxsHet, idxsCT) if (nbrOfHoms > 0) { idxsHom <- intersect(idxsHom, idxsCT) } idxsHetNonDH <- setdiff(idxsHet, idxsDH) if (verbose) { cat(verbose, "Heterozygous SNPs to resample for TCN:") str(verbose, idxsHet) cat(verbose, "Homozygous SNPs to resample for TCN:") str(verbose, idxsHom) cat(verbose, "Non-polymorphic loci to resample for TCN:") str(verbose, idxsNonSNP) cat(verbose, "Heterozygous SNPs with non-DH to resample for TCN:") str(verbose, idxsHetNonDH) } # Note that length(idxsHetNonDH) may differ from zero in case CT is non-missing # but rho is missing, e.g. CT = sum(c(thetaA,thetaB), na.rm=TRUE) and # thetaB is missing. /HB 2010-12-01 idxsTCN <- sort(unique(c(idxsHet, idxsHom, idxsNonSNP))) if (verbose) { cat(verbose, "Loci to resample for TCN:") str(verbose, idxsTCN) } # Sanity check if (.validate) { .stop_if_not(length(idxsHet) + length(idxsHom) + length(idxsNonSNP) == nbrOfTCNs) .stop_if_not(length(intersect(idxsDH, idxsHetNonDH)) == 0L) .stop_if_not(length(idxsTCN) == nbrOfTCNs) } verbose && exit(verbose) # These numbers should be preserved when the resampling verbose && printf(verbose, "Number of (#hets, #homs, #nonSNPs): (%d,%d,%d)\n", length(idxsHet), length(idxsHom), length(idxsNonSNP)) # Workaround: ... Why? /HB 2013-10-22 shouldHaveDHs <- (nbrOfDHs > 0L && !is.na(dhMeans[jj])) if (!shouldHaveDHs) { idxsHetNonDH <- idxsDH .stop_if_not(all(idxsHetNonDH > 0L)) } shouldHaveDHs <- NULL # Not needed anymore nHoms <- length(idxsHom) nNonSNPs <- length(idxsNonSNP) nHetNonDHs <- length(idxsHetNonDH) locusSetJJ <- list( segment = segJJ, loci = list( all = idxsAll, snp = idxsSNP, tcn = idxsTCN, dh = idxsDH, nonSnp = idxsNonSNP, het = idxsHet, hom = idxsHom, hetNonDh = idxsHetNonDH ) ) # Sanity checks if (.validate) { loci <- locusSetJJ$loci for (key in names(loci)) { idxs <- loci[[key]] # Assert positive indices .stop_if_not(all(idxs > 0L)) # Assert a unique set of indices .stop_if_not(!any(duplicated(idxs))) } # Assert non-overlapping sets with(loci, { .stop_if_not(length(intersect(dh, hetNonDh)) == 0L) .stop_if_not(length(intersect(het, hom)) == 0L) .stop_if_not(length(intersect(het, nonSnp)) == 0L) .stop_if_not(length(intersect(hom, nonSnp)) == 0L) }) loci <- NULL # Not needed anymore } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify bootstrap locus sets preserving (#hets, #homs, #nonSNPs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identifying bootstrap locus sets that preservs (#hets, #homs, #nonSNPs)") verbose && cat(verbose, "Number of bootstrap samples: ", B) nbrOfTCNs <- nbrOfDHs+nHoms+nNonSNPs nbrOfHets <- nbrOfDHs+nHetNonDHs # Allocate index matrices tcn <- matrix(NA_integer_, nrow=nbrOfTCNs, ncol=B) dh <- matrix(NA_integer_, nrow=nbrOfDHs, ncol=B) nonSnp <- matrix(NA_integer_, nrow=nNonSNPs, ncol=B) het <- matrix(NA_integer_, nrow=nbrOfHets, ncol=B) hom <- matrix(NA_integer_, nrow=nHoms, ncol=B) hetNonDh <- matrix(NA_integer_, nrow=nHetNonDHs, ncol=B) ## resample <- function(x, size, ...) { ## .stop_if_not(size == length(x)) ## x ## } # resample() # (1) Bootstrap DH loci if (nbrOfDHs > 0L) { # (a) Resample heterozygous SNPs (=> resampled DH units) for (bb in seq_len(B)) { dh[,bb] <- resample(idxsDH, size=nbrOfDHs, replace=TRUE) } } # (2) Bootstrap other loci # (a) Resample non-DH hets SNPs if (nHetNonDHs > 0L) { for (bb in seq_len(B)) { idxsHetNonDHBB <- resample(idxsHetNonDH, size=nHetNonDHs, replace=TRUE) hetNonDh[,bb] <- idxsHetNonDHBB } } # (b) Resample homozygous SNPs if (nHoms > 0L) { for (bb in seq_len(B)) { idxsHomBB <- resample(idxsHom, size=nHoms, replace=TRUE) hom[,bb] <- idxsHomBB } } # (c) Resample non-SNPs if (nNonSNPs > 0L) { for (bb in seq_len(B)) { idxsNonSNPBB <- resample(idxsNonSNP, size=nNonSNPs, replace=TRUE) nonSnp[,bb] <- idxsNonSNPBB } } # (d) Resampled hets if (nbrOfHets > 0L) { for (bb in seq_len(B)) { idxsDHBB <- dh[,bb] idxsHetNonDHBB <- hetNonDh[,bb] idxsHetBB <- c(idxsDHBB, idxsHetNonDHBB) # idxsHetBB <- sort(idxsHetBB) het[,bb] <- idxsHetBB } } # (e) Update TCN loci if (nbrOfTCNs > 0L) { for (bb in seq_len(B)) { idxsHetBB <- het[,bb] idxsHomBB <- hom[,bb] idxsNonSNPBB <- nonSnp[,bb] idxsTCNBB <- c(idxsHetBB, idxsHomBB, idxsNonSNPBB) # idxsTCNBB <- sort(idxsTCNBB) tcn[,bb] <- idxsTCNBB } } # Record locusSetJJ$bootstrap <- list( B = B, loci = list( tcn = tcn, dh = dh, nonSnp = nonSnp, het = het, hom = hom, hetNonDh = hetNonDh ) ) # Sanity check if (.validate) { loci <- locusSetJJ$loci lociB <- locusSetJJ$bootstrap$loci for (key in names(lociB)) { idxs <- loci[[key]] idxsB <- lociB[[key]] idxsB <- unique(sort(idxsB)) .stop_if_not(all(is.element(idxsB, idxs))) } loci <- lociB <- NULL # Not needed anymore } verbose && exit(verbose) # Record locusSet[[jj]] <- locusSetJJ # Not needed anymore locusSetJJ <- NULL verbose && exit(verbose) } # for (jj ...) # Sanity checks .stop_if_not(is.list(locusSet)) .stop_if_not(length(locusSet) == nbrOfSegments) verbose && exit(verbose) res$locusSet <- locusSet res }, protected=TRUE) # getBootstrapLocusSets() ############################################################################## # HISTORY # 2013-10-22 # o Added Rdoc comments. # o Added getBootstrapLocusSets() for PairedPSCBS. ############################################################################## PSCBS/R/CBS.PLOT,many.R0000644000176200001440000001532514564051545013614 0ustar liggesuserssetMethodS3("tileChromosomes", "CBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # Nothing to do, i.e. already tiled? if (isTRUE(attr(fit, "tiledChromosomes"))) { return(fit) } verbose && enter(verbose, "Tiling chromosomes") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segs <- getSegments(fit) knownSegments <- fit$params$knownSegments # Identify all chromosome chromosomes <- getChromosomes(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Additional chromosome annotations # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - chrStats <- getChromosomeRanges(fit) # Build an "empty" row with start == 1. chrStatsKK <- chrStats[1,,drop=FALSE][NA,,drop=FALSE] chrStatsKK[,"start"] <- 1L # Append empty row chrStats <- rbind(chrStats, chrStatsKK) # Offset (start,stop) chrOffsets <- getChromosomeOffsets(fit, ...) chrStats[,"start"] <- chrStats[,"start"] + chrOffsets chrStats[,"end"] <- chrStats[,"end"] + chrOffsets # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Offset... # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segFields <- grep("(start|end)$", colnames(segs), value=TRUE) for (kk in seq_along(chromosomes)) { chromosome <- chromosomes[kk] chrTag <- sprintf("Chr%02d", chromosome) verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", kk, chrTag, length(chromosomes))) # Get offset for this chromosome offset <- chrOffsets[kk] verbose && cat(verbose, "Offset: ", offset) # Offset data idxs <- which(data$chromosome == chromosome) if (length(idxs) > 0L) { data$x[idxs] <- offset + data$x[idxs] } # Offset segmentation idxs <- which(segs$chromosome == chromosome) if (length(idxs) > 0L) { segs[idxs,segFields] <- offset + segs[idxs,segFields] } # Offset known segments idxs <- which(knownSegments$chromosome == chromosome) if (length(idxs) > 0L) { knownSegments[idxs,c("start", "end")] <- offset + knownSegments[idxs,c("start", "end")] } verbose && exit(verbose) } # for (kk ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- fit fitT$data <- data fitT$output <- segs fitT$chromosomeStats <- chrStats fitT$params$knownSegments <- knownSegments fitT$params$chrOffsets <- chrOffsets # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity checks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - segs <- getSegments(fit) segsT <- getSegments(fitT) segs <- segs[,!is.element(colnames(segs), c("start", "end"))] segsT <- segsT[,!is.element(colnames(segsT), c("start", "end"))] .stop_if_not(all.equal(segsT, segs)) data <- getLocusData(fit) dataT <- getLocusData(fitT) data <- data[,!is.element(colnames(data), c("x"))] dataT <- dataT[,!is.element(colnames(dataT), c("x"))] .stop_if_not(all.equal(dataT, data)) .stop_if_not(nbrOfLoci(fitT) == nbrOfLoci(fit)) .stop_if_not(nbrOfSegments(fitT) == nbrOfSegments(fit)) # Flag object attr(fitT, "tiledChromosomes") <- TRUE verbose && exit(verbose) fitT }, protected=TRUE) # tileChromosomes() setMethodS3("plotTracksManyChromosomes", "CBS", function(x, scatter=TRUE, pch=20, col="gray", meanCol="purple", Clim=c(0,3*ploidy(x)), xScale=1e-6, xlab="Genomic position", Clab="TCN", ..., boundaries=TRUE, levels=TRUE, subset=NULL, byIndex=FALSE, add=FALSE, onBegin=NULL, onEnd=NULL, mar=NULL, verbose=FALSE) { # To please R CMD check fit <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': # Argument 'add': add <- Arguments$getLogical(add) # Argument 'Clim': if (!add) { Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Argument 'subset': if (!is.null(subset)) { subset <- Arguments$getDouble(subset, range=c(0,1)) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Tile chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitT <- tileChromosomes(fit) verbose && str(verbose, fitT) # Sanity check .stop_if_not(!is.null(fitT$chromosomeStats)) # Extract the input data data <- getLocusData(fitT) if (is.null(data)) { stop("Cannot plot segmentation results. No input data available.") } # Subset of the loci? if (!is.null(subset) && subset < 1) { n <- nrow(data) keep <- sample(n, size=subset*n) data <- data[keep,] } # To please R CMD check CT <- y <- muN <- betaT <- betaN <- betaTN <- NULL rm(list=c("CT", "muN", "betaT", "betaN", "betaTN")) attachLocally(data) x <- xScale * x chrStats <- fitT$chromosomeStats chrStats <- chrStats[-nrow(chrStats),,drop=FALSE] chrRanges <- as.matrix(chrStats[,c("start","end")]) vs <- xScale * chrRanges mids <- (vs[,1]+vs[,2])/2 CT <- y nbrOfLoci <- length(x) chromosomes <- getChromosomes(fitT) chrLabels <- sprintf("%02d", chromosomes) if (byIndex) { xs <- seq_along(x) } else { xs <- x } if (!add && !is.null(mar)) { par(mar=mar) } gh <- fitT gh$xScale <- xScale xlim <- xScale*range(chrRanges, na.rm=TRUE) pchT <- if (scatter) { pch } else { NA } plot(NA, xlim=xlim, ylim=Clim, xlab=xlab, ylab=Clab, axes=FALSE) if (!is.null(onBegin)) onBegin(gh=gh) points(xs, CT, pch=pchT, col=col, ...) side <- rep(c(1,3), length.out=length(chrLabels)) mtext(text=chrLabels, side=side, at=mids, line=0.1, cex=0.7*par("cex")) if (boundaries) { abline(v=vs, lty=3) } axis(side=2) box() if (levels) { drawLevels(fitT, col=meanCol, xScale=xScale, byIndex=byIndex) } if (!is.null(onEnd)) onEnd(gh=gh) invisible(gh) }, private=TRUE) # plotTracksManyChromosomes() PSCBS/R/PairedPSCBS.RESTRUCT.R0000644000176200001440000002040314564051545014731 0ustar liggesuserssetMethodS3("extractSegments", "PairedPSCBS", function(this, idxs, ..., verbose=FALSE) { fit <- this # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - updateSegRows <- function(segRows, idxs=NULL) { verbose && str(verbose, segRows) if (!is.null(idxs)) { segRows <- segRows[idxs,,drop=FALSE] } # verbose && cat(verbose, "Number of segments: ", nrow(segRows)) # verbose && str(verbose, segRows) # Treat splitters separately isSplitter <- (is.na(segRows[,1]) & is.na(segRows[,2])) ns <- segRows[,2] - segRows[,1] + 1L # verbose && cat(verbose, "Number of loci per segment:") # verbose && str(verbose, ns) ns <- ns[!isSplitter] from <- c(1L, cumsum(ns)[-length(ns)]+1L) to <- from + (ns - 1L) segRows[!isSplitter,1] <- from segRows[!isSplitter,2] <- to verbose && str(verbose, segRows) # Sanity check ns2 <- segRows[,2] - segRows[,1] + 1L ns2 <- ns2[!isSplitter] .stop_if_not(all(ns2 == ns)) segRows } # updateSegRows() # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'idxs': idxs <- Arguments$getIndices(idxs, max=nbrOfSegments(fit, splitters=TRUE)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Extracting subset of segments") verbose && cat(verbose, "Number of segments: ", length(idxs)) verbose && str(verbose, idxs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) tcnSegRows <- fit$tcnSegRows dhSegRows <- fit$dhSegRows segs <- getSegments(fit) params <- fit$params # Sanity checks .stop_if_not(all(!is.na(data$chromosome) & !is.na(data$x))) .stop_if_not(length(tcnSegRows) == length(dhSegRows)) # Sanity checks if (!params$joinSegments) { stop("Cannot extract subset of segments unless CNs are segmented using joinSegments=TRUE.") } if (params$flavor == "tcn,dh") { stop("NOT IMPLEMENTED: Extracting a subset of segments is not supported for flavor '", params$flavor, "'.") } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update table of segments") segsT <- segs[idxs,,drop=FALSE] verbose && str(verbose, segsT) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset data accordingly # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update locus data") segRows <- tcnSegRows segRows <- segRows[idxs,,drop=FALSE] from <- segRows[[1]] to <- segRows[[2]] ok <- (!is.na(from) & !is.na(to)) from <- from[ok] to <- to[ok] keep <- logical(nrow(data)) for (rr in seq_along(from)) { keep[from[rr]:to[rr]] <- TRUE } keep <- which(keep) verbose && printf(verbose, "Identified %d (%.2f%%) of %d data rows:\n", length(keep), 100*length(keep)/nrow(data), nrow(data)) verbose && str(verbose, keep) dataT <- data[keep,,drop=FALSE] verbose && str(verbose, dataT) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update 'segRows' # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update 'segRows'") segRows <- updateSegRows(tcnSegRows, idxs=idxs) d <- tcnSegRows[idxs,] - segRows # Sanity check .stop_if_not(identical(d[,1], d[,2])) d <- d[,1] verbose && cat(verbose, "Row deltas:") verbose && str(verbose, d) tcnSegRows <- tcnSegRows[idxs,,drop=FALSE] - d verbose && str(verbose, tcnSegRows) # Sanity checks segRows <- tcnSegRows .stop_if_not(suppressWarnings(max(segRows, na.rm=TRUE)) <= nrow(dataT)) drow <- segRows[-1,1] - segRows[-nrow(segRows),2] if (!all(is.na(drow) | (drow > 0))) { print(segRows) stop("INTERNAL ERROR: Generated 'tcnSegRows' is invalid, because it contains overlapping data chunks.") } dhSegRows <- dhSegRows[idxs,,drop=FALSE] - d verbose && str(verbose, dhSegRows) # Sanity checks segRows <- dhSegRows .stop_if_not(suppressWarnings(max(segRows, na.rm=TRUE)) <= nrow(dataT)) drow <- segRows[-1,1] - segRows[-nrow(segRows),2] .stop_if_not(all(is.na(drow) | (drow > 0))) if (!all(is.na(drow) | (drow > 0))) { print(segRows) stop("INTERNAL ERROR: Generated 'dhSegRows' is invalid, because it contains overlapping data chunks.") } verbose && exit(verbose) # Create new object res <- fit res$data <- dataT res$output <- segsT res$tcnSegRows <- tcnSegRows res$dhSegRows <- dhSegRows verbose && exit(verbose) res }, protected=TRUE) # extractSegments() ###########################################################################/** # @set "class=PairedPSCBS" # @RdocMethod mergeTwoSegments # # @title "Merge two neighboring segments" # # \description{ # @get "title" by recalculating segment statistics. # } # # @synopsis # # \arguments{ # \item{left}{An @integer specifying the segments (left, left+1) # to be merged.} # \item{update}{If @TRUE, segment statistics are updated.} # \item{verbose}{A @logical or a @see "R.utils::Verbose" object.} # \item{...}{Not used.} # } # # \value{ # Returns a @see "PairedPSCBS" with one less segment. # } # # @author "HB" # # \seealso{ # To drop regions (a connected set of segments) see \code{dropRegions()}. # @seeclass # } #*/########################################################################### setMethodS3("mergeTwoSegments", "PairedPSCBS", function(this, left, update=TRUE, verbose=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(this, splitters=TRUE) # Argument 'left': left <- Arguments$getIndex(left, max=nbrOfSegments-1L) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Merging two segments") verbose && printf(verbose, "Segments to be merged: %s & %s\n", left, left+1) verbose && cat(verbose, "Number of segments before merging: ", nbrOfSegments) verbose && cat(verbose, "Number of segments after merging: ", nbrOfSegments-1L) segs <- getSegments(this, splitters=TRUE) tcnSegRows <- this$tcnSegRows dhSegRows <- this$dhSegRows rows <- c(left,left+1) segsT <- segs[rows,,drop=FALSE] # Sanity check chrs <- segsT[["chromosome"]] if (chrs[1] != chrs[2]) { stop("Cannot merge segments that are on different chromosomes: ", chrs[1], " != ", chrs[2]) } # Merge segments segT <- segsT[1,] fields <- colnames(segsT) # (chromosome, tcnId, dhId) idxsUsed <- 1:3 # Starts idxs <- grep("Start$", fields) T <- as.matrix(segsT[,idxs,drop=FALSE]) segT[,idxs] <- colMins(T, na.rm=TRUE, useNames=FALSE) idxsUsed <- c(idxsUsed, idxs) # Ends idxs <- grep("End$", fields) T <- as.matrix(segsT[,idxs,drop=FALSE]) segT[,idxs] <- colMaxs(T, na.rm=TRUE, useNames=FALSE) idxsUsed <- c(idxsUsed, idxs) # Counts idxs <- grep("NbrOf", fields) segT[,idxs] <- colSums(segsT[,idxs,drop=FALSE]) idxsUsed <- c(idxsUsed, idxs) # "Invalidate" remaining entries if (update) { idxsTodo <- setdiff(seq_along(fields), idxsUsed) segT[,idxsTodo] <- NA } # Update segment table segs[rows[1],] <- segT segs <- segs[-rows[2],] # Update 'segRows' tables segRows <- tcnSegRows segRows[rows[1],2] <- segRows[rows[2],2] segRows <- segRows[-rows[2],] tcnSegRows <- segRows segRows <- dhSegRows segRows[rows[1],2] <- segRows[rows[2],2] segRows <- segRows[-rows[2],] dhSegRows <- segRows # Create results object res <- this res$output <- segs res$tcnSegRows <- tcnSegRows res$dhSegRows <- dhSegRows # Update the segment statistics? if (update) { res <- updateMeans(res) } verbose && exit(verbose) res }, private=TRUE) PSCBS/R/prememoize.R0000644000176200001440000000253714564051545013644 0ustar liggesusers.setupCacheRootPath <- function(...) { # Setup the cache root path, possibly by prompting the user. ns <- getNamespace("R.cache") setupCacheRootPath <- get("setupCacheRootPath", mode="function", envir=ns) setupCacheRootPath() } # .setupCacheRootPath() # CRAN POLICY: Add precalculated memoization files to the R.cache # directory, unless running interactively. The reason for doing this # is solely to make segmentBy[Non]PairedPSCBS examples to run faster # on R CMD check but not having to create these memoized files. # /HB 2012-11-05 # UPDATE: Now it will also gain first-time users. /HB 2013-09-27 .prememoize <- function(verbose=FALSE) { # Explictly setup cache root here, since it's only done by 'R.cache' # if that package is attached. Here we only load it. /HB 2013-09-27 .setupCacheRootPath() # This will make sure that the pre-generated calculations available # in the 'PSCBS' package are copied to the R.cache cache directory. # This regardless of whether a 'PSCBS' cache subdirectory exists # or not. /HB 2013-09-27 path <- "PSCBS/segmentByCBS/sbdry" pathS <- system.file("misc/_Rcache", path, package="PSCBS") pathD <- getCachePath(path) copyDirectory(pathS, pathD, copy.mode=FALSE, recursive=FALSE, overwrite=TRUE) if (verbose) { message("Added pre-memoized calculations: ", getAbsolutePath(pathD)) } } # .prememoize() PSCBS/R/CNA.EXTS.R0000644000176200001440000000066714564051545012655 0ustar liggesuserssetMethodS3("segmentByCBS", "CNA", function(y, ...) { # To please R CMD check cnData <- y # Extract signals of interest chromosome <- cnData$chrom x <- cnData$maploc y <- cnData[,3] signalType <- attr(cnData, "data.type") sampleName <- colnames(cnData)[3] # str(list(y=y, chromosome=chromosome, x=x)) fit <- segmentByCBS(y=y, chromosome=chromosome, x=x, ...) sampleName(fit) <- sampleName fit }) # segmentByCBS() PSCBS/R/PairedPSCBS.estimateDeltaLOH.R0000644000176200001440000001700014564202700016574 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateDeltaLOH # # @title "Estimate a threshold for calling LOH from DH" # # \description{ # @get "title" to be used by the @seemethod "callLOH" method. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # estimator to use.} # \item{...}{Additional arguments passed to the estimator.} # \item{max}{(Optional) The maximum estimate allowed. If greater than # this value, the estimate will be truncated.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the threshold estimate as a @numeric scalar or -@Inf. # In case it is not possible to estimate the LOH threshold, then # -@Inf is returned. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "estimateDeltaLOHByMinC1ForNonAB". # } # #*/########################################################################### setMethodS3("estimateDeltaLOH", "PairedPSCBS", function(this, flavor=c("minC1|nonAB"), ..., max=Inf, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'max': max <- Arguments$getDouble(max, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating DH threshold for calling LOH") verbose && cat(verbose, "flavor: ", flavor) if (flavor == "minC1|nonAB") { delta <- estimateDeltaLOHByMinC1ForNonAB(this, ..., verbose=verbose) } else { stop("Unkown flavor: ", flavor) } verbose && printf(verbose, "delta: %.3g\n", delta) # Truncate estimate? if (delta > max) { warning("Estimated delta (%.3g) was greater than the maximum allowed value (%.3g). The latter will be used instead.", delta, max) delta <- max verbose && printf(verbose, "Max delta: %.3g\n", max) verbose && printf(verbose, "Truncated delta: %.3g\n", delta) } verbose && exit(verbose) delta }) # estimateDeltaLOH() ###########################################################################/** # @set class=PairedPSCBS # @RdocMethod estimateDeltaLOHByMinC1ForNonAB # # @title "Estimate a threshold for calling LOH from DH" # # \description{ # @get "title" based on the location of guessed C1=0 and C1=1 peaks. # } # # @synopsis # # \arguments{ # \item{midpoint}{A @numeric scalar in [0,1] specifying the relative # position of the midpoint between the estimated locations of # C1=0 and C1=1 mean parameters.} # \item{maxC}{Maximum total copy number of a segment in order to # be included in the initial set of segments.} # \item{...}{Not used.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns the estimated LOH threshold as a @numeric scalar or -@Inf. # In case it is not possible to estimate the LOH threshold, then # -@Inf is returned. # } # # \details{ # This method requires that calls for allelic balances already have # been me made, cf. @seemethod "callAllelicBalance". # } # # \section{Algorithm}{ # \itemize{ # \item Grabs the segment-level C1 estimates. # \item Calculate segment weights proportional to the number of heterozygous SNPs. # \item Estimate the C1=1 location as the weighted median C1 for segments that have been called to be in allelic balance. # \item Estimate the C1=0 location as the smallest C1 among segments that are not in allelic balance. # \item Let the LOH threshold be the midpoint of the estimates C1=0 and C1=1 locations. # } # } # # @author "HB" # # \seealso{ # Instead of calling this method explicitly, it is recommended # to use the @seemethod "estimateDeltaLOH" method. # } # # @keyword internal #*/########################################################################### setMethodS3("estimateDeltaLOHByMinC1ForNonAB", "PairedPSCBS", function(this, midpoint=1/2, maxC=3*(ploidy(this)/2), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'midpoint': midpoint <- Arguments$getDouble(midpoint, range=c(0,1)) # Argument 'maxC': maxC <- Arguments$getDouble(maxC, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Estimating DH threshold for calling LOH as the midpoint between guessed C1=0 and C1=1") segs <- getSegments(this, splitters=FALSE) nbrOfSegments <- nrow(segs) verbose && printf(verbose, "Argument 'midpoint': %.3g\n", midpoint) verbose && cat(verbose, "Number of segments: ", nbrOfSegments) # Getting AB calls isAB <- segs$abCall if (is.null(isAB)) { stop("Cannot estimate delta_LOH because allelic-balance calls have not been made yet.") } nbrOfAB <- sum(isAB, na.rm=TRUE) verbose && printf(verbose, "Number of segments in allelic balance: %d (%.1f%%) of %d\n", nbrOfAB, 100*nbrOfAB/nbrOfSegments, nbrOfSegments) # Sanity check if (nbrOfAB == 0) { stop("There are no segments in allelic balance.") } nbrOfNonAB <- sum(!isAB, na.rm=TRUE) verbose && printf(verbose, "Number of segments not in allelic balance: %d (%.1f%%) of %d\n", nbrOfNonAB, 100*nbrOfNonAB/nbrOfSegments, nbrOfSegments) segsNonAB <- segs[which(!isAB),,drop=FALSE] # Sanity check if (nbrOfNonAB == 0) { msg <- sprintf("All %d segments are in allelic balance. Cannot estimate DeltaLOH, which requires that at least one segment must be in allelic imbalance. Returning -Inf instead.", nbrOfSegments) warning(msg) return(-Inf) } # Identify segments in AB and with small enough TCNs C <- segs$tcnMean keep <- which(isAB & C <= maxC) verbose && printf(verbose, "Number of segments in allelic balance and TCN <= %.2f: %d (%.1f%%) of %d\n", maxC, length(keep), 100*length(keep)/nbrOfSegments, nbrOfSegments) # Sanity check if (length(keep) == 0) { stop("There are no segments in allelic balance with small enough total CN.") } # (a) Estimate mean C1 level of AB segments segsT <- segs[keep,,drop=FALSE] C <- segsT$tcnMean n <- segsT$dhNbrOfLoci w <- n/sum(n) C1 <- C/2 # Called AB! verbose && printf(verbose, "C: %s\n", hpaste(sprintf("%.3g", C))) verbose && printf(verbose, "Corrected C1 (=C/2): %s\n", hpaste(sprintf("%.3g", C1))) verbose && printf(verbose, "Number of DHs: %s\n", hpaste(n)) verbose && printf(verbose, "Weights: %s\n", hpaste(sprintf("%.3g", w))) muC1atAB <- weightedMedian(C1, w=w, na.rm=TRUE) verbose && printf(verbose, "Weighted median of (corrected) C1 in allelic balance: %.3f\n", muC1atAB) # (b) Estimate mean C1 level of non-AB segments C1 <- segsNonAB$c1Mean muC1atNonAB <- min(C1, na.rm=TRUE) idxs <- which(C1 <= muC1atNonAB) n <- segsNonAB$dhNbrOfLoci[idxs] verbose && printf(verbose, "Smallest C1 among segments not in allelic balance: %.3g\n", muC1atNonAB) verbose && printf(verbose, "There are %d segments with in total %d heterozygous SNPs with this level.\n", length(idxs), n) # Sanity check .stop_if_not(muC1atNonAB < muC1atAB) delta <- midpoint * (muC1atAB + muC1atNonAB) verbose && printf(verbose, "Midpoint between the two: %.3g\n", delta) verbose && exit(verbose) delta }, private=TRUE) # estimateDeltaLOHByMinC1AtNonAB() PSCBS/R/CBS.RESTRUCT.R0000644000176200001440000002304214564051545013343 0ustar liggesuserssetMethodS3("shiftTCN", "CBS", function(fit, shift, update=TRUE, ...) { # Argument 'shift': shift <- Arguments$getDouble(shift, disallow=c("NA", "NaN", "Inf")) data <- getLocusData(fit) data$y <- data$y + shift fit$data <- data # Not needed anymore data <- NULL if (update) { fit <- updateMeans(fit, ...) } fit }, protected=TRUE) ###########################################################################/** # @set "class=CBS" # @RdocMethod c # @alias c.PSCBS # # @title "Concatenates segmentation results" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{\dots}{One or more @see "AbstractCBS" objects to be combined.} # \item{addSplit}{If @TRUE, a "divider" is added between chromosomes.} # } # # \value{ # Returns an @see "AbstractCBS" object of the same class in \dots. # } # # @author "HB" # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("c", "CBS", function(..., addSplit = TRUE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - args <- list(...) ## Nothing todo? nargs <- length(args) if (nargs == 1) return(args[[1]]) isNA <- function(x) is.logical(x) && length(x) == 1L && is.na(x) res <- args[[1]] fields <- c("output", "segRows") for (ii in 2:nargs) { arg <- args[[ii]] if (isNA(arg)) { if (addSplit) { warning(sprintf("Detected explicit NA in call to c(<%s>, ..., addSplit = TRUE). Ignoring", class(args[[1]])[1])) next } ## Add "splitter" for (field in fields) { res[[field]] <- rbind(res[[field]], NA) } } else { ## Locus-level data data <- getLocusData(res) data_arg <- getLocusData(arg) if (!all(colnames(data_arg) == colnames(data))) { stop(sprintf("Cannot concatenate %s and %s objects, because they have different sets of columns in field %s: {%s} [n=%d] != {%s} [n=%d]", sQuote(class(res)[1]), sQuote(class(arg)[1]), sQuote(field), paste(sQuote(colnames(data)), collapse=", "), ncol(data), paste(sQuote(colnames(data_arg)), collapse=", "), ncol(data_arg))) } indexOffset <- nrow(data) data <- rbind(data, getLocusData(arg)) res[["data"]] <- data # Segmentation data for (field in fields[-1]) { arg[[field]] <- arg[[field]] + indexOffset } splitter <- if (addSplit) NA else NULL for (field in fields) { res[[field]] <- rbind(res[[field]], splitter, arg[[field]]) } # Known segments ksT <- res$params$knownSegments ksT$length <- NULL # In case it's been added ksO <- arg$params$knownSegments ksO$length <- NULL # In case it's been added res$params$knownSegments <- rbind(ksT, ksO) } } ## for (ii ...) ## Drop row names, iff they've been added for (field in fields) rownames(res[[field]]) <- NULL # Sanity check ns <- sapply(res[fields], FUN = nrow) .stop_if_not(all(ns == ns[1])) res }) # c() setMethodS3("extractSegments", "CBS", function(this, idxs, ..., verbose=FALSE) { fit <- this # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - updateSegRows <- function(segRows, idxs=NULL) { verbose && str(verbose, segRows) if (!is.null(idxs)) { segRows <- segRows[idxs,,drop=FALSE] } # verbose && cat(verbose, "Number of segments: ", nrow(segRows)) # verbose && str(verbose, segRows) # Treat splitters separately isSplitter <- (is.na(segRows[,1]) & is.na(segRows[,2])) ns <- segRows[,2] - segRows[,1] + 1L # verbose && cat(verbose, "Number of loci per segment:") # verbose && str(verbose, ns) ns <- ns[!isSplitter] from <- c(1L, cumsum(ns)[-length(ns)]+1L) to <- from + (ns - 1L) segRows[!isSplitter,1] <- from segRows[!isSplitter,2] <- to verbose && str(verbose, segRows) # Sanity check ns2 <- segRows[,2] - segRows[,1] + 1L ns2 <- ns2[!isSplitter] .stop_if_not(all(ns2 == ns)) segRows } # updateSegRows() # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'idxs': idxs <- Arguments$getIndices(idxs, max=nbrOfSegments(fit, splitters=TRUE)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Extracting subset of segments") verbose && cat(verbose, "Number of segments: ", length(idxs)) verbose && str(verbose, idxs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) segRows <- fit$segRows segs <- getSegments(fit) params <- fit$params # Sanity checks .stop_if_not(all(!is.na(data$chromosome) & !is.na(data$x))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update table of segments") segsT <- segs[idxs,,drop=FALSE] verbose && str(verbose, segsT) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset data accordingly # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update locus data") segRowsT <- segRows[idxs,,drop=FALSE] from <- segRowsT[[1]] to <- segRowsT[[2]] ok <- (!is.na(from) & !is.na(to)) from <- from[ok] to <- to[ok] keep <- logical(nrow(data)) for (rr in seq_along(from)) { keep[from[rr]:to[rr]] <- TRUE } keep <- which(keep) verbose && printf(verbose, "Identified %d (%.2f%%) of %d data rows:\n", length(keep), 100*length(keep)/nrow(data), nrow(data)) verbose && str(verbose, keep) dataT <- data[keep,,drop=FALSE] verbose && str(verbose, dataT) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update 'segRows' # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Update 'segRows'") segRowsT <- updateSegRows(segRowsT) d <- segRows[idxs,] - segRowsT # Sanity check .stop_if_not(identical(d[,1], d[,2])) d <- d[,1] verbose && cat(verbose, "Row deltas:") verbose && str(verbose, d) segRows <- segRows[idxs,,drop=FALSE] - d verbose && str(verbose, segRows) # Sanity checks .stop_if_not(suppressWarnings(max(segRows, na.rm=TRUE)) <= nrow(dataT)) drow <- segRows[-1,1] - segRows[-nrow(segRows),2] .stop_if_not(all(is.na(drow) | (drow > 0))) if (!all(is.na(drow) | (drow > 0))) { print(segRows) stop("INTERNAL ERROR: Generated 'segRows' is invalid, because it contains overlapping data chunks.") } verbose && exit(verbose) # Create new object res <- fit res$data <- dataT res$output <- segsT res$segRows <- segRows verbose && exit(verbose) res }, protected=TRUE) # extractSegments() setMethodS3("mergeTwoSegments", "CBS", function(this, left, update=TRUE, verbose=FALSE, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(this, splitters=TRUE) # Argument 'left': left <- Arguments$getIndex(left, max=nbrOfSegments-1L) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Merging two segments") verbose && printf(verbose, "Segments to be merged: %s & %s\n", left, left+1) verbose && cat(verbose, "Number of segments before merging: ", nbrOfSegments) verbose && cat(verbose, "Number of segments after merging: ", nbrOfSegments-1L) segs <- getSegments(this) segRows <- this$segRows rows <- c(left,left+1) segsT <- segs[rows,,drop=FALSE] # Sanity check chrs <- segsT[["chromosome"]] if (chrs[1] != chrs[2]) { stop("Cannot merge segments that are on different chromosomes: ", chrs[1], " != ", chrs[2]) } # Merge segments segT <- segsT[1,] fields <- colnames(segsT) idxsUsed <- c() # (id) [as in label] idxs <- grep("(I|i)d$", fields) idxsUsed <- c(idxsUsed, idxs) # (chromosome) idxs <- grep("chromosome$", fields) idxsUsed <- c(idxsUsed, idxs) # Starts idxs <- grep("(S|s)tart$", fields) T <- as.matrix(segsT[,idxs,drop=FALSE]) segT[,idxs] <- colMins(T, na.rm=TRUE, useNames=FALSE) idxsUsed <- c(idxsUsed, idxs) # Ends idxs <- grep("(E|e)nd$", fields) T <- as.matrix(segsT[,idxs,drop=FALSE]) segT[,idxs] <- colMaxs(T, na.rm=TRUE, useNames=FALSE) idxsUsed <- c(idxsUsed, idxs) # Counts idxs <- grep("(N|n)brOf", fields) segT[,idxs] <- colSums(segsT[,idxs,drop=FALSE]) idxsUsed <- c(idxsUsed, idxs) # "Invalidate" remaining entries idxsTodo <- setdiff(seq_along(fields), idxsUsed) segT[,idxsTodo] <- NA # Update segment table segs[rows[1],] <- segT segs <- segs[-rows[2],] # Update 'segRows' tables segRows[rows[1],2] <- segRows[rows[2],2] segRows <- segRows[-rows[2],] # Create results object res <- this res$output <- segs res$segRows <- segRows # Update the segment statistics? if (update) { res <- updateMeans(res) } verbose && exit(verbose) res }, protected=TRUE) # mergeTwoSegments() PSCBS/R/segmentByCBS.R0000644000176200001440000010626515000476656013760 0ustar liggesusers###########################################################################/** # @RdocDefault segmentByCBS # @alias segmentByCBS.data.frame # @alias segmentByCBS.CBS # @alias segmentByCBS.CNA # @alias segmentByCBS # # @title "Segment genomic signals using the CBS method" # # \description{ # @get "title" of the \pkg{DNAcopy} package. # This is a convenient low-level wrapper for the \code{DNAcopy::segment()} # method. It is intended to be applied to a sample at the time. # For more details on the Circular Binary Segmentation (CBS) method # see [1,2]. # } # # @synopsis # # \arguments{ # \item{y}{A @numeric @vector of J genomic signals to be segmented.} # \item{chromosome}{Optional @numeric @vector of length J, specifying # the chromosome of each loci. If a scalar, it is expanded to # a vector of length J.} # \item{x}{Optional @numeric @vector of J genomic locations. # If @NULL, index locations \code{1:J} are used.} # \item{index}{An optional @integer @vector of length J specifying # the genomewide indices of the loci.} # \item{w}{Optional @numeric @vector in [0,1] of J weights.} # \item{undo}{A non-negative @numeric. If greater than zero, then # arguments \code{undo.splits="sdundo"} and \code{undo.SD=undo} # are passed to \code{DNAcopy::segment()}. # In the special case when \code{undo} is +@Inf, the segmentation # result will not contain any changepoints (in addition to what # is specified by argument \code{knownSegments}).} # \item{avg}{A @character string specifying how to calculating # segment mean levels \emph{after} change points have been # identified.} # \item{...}{Additional arguments passed to the \code{DNAcopy::segment()} # segmentation function.} # \item{joinSegments}{If @TRUE, there are no gaps between neighboring # segments. # If @FALSE, the boundaries of a segment are defined by the support # that the loci in the segments provides, i.e. there exist a locus # at each end point of each segment. This also means that there # is a gap between any neighboring segments, unless the change point # is in the middle of multiple loci with the same position. # The latter is what \code{DNAcopy::segment()} returns. # } # \item{knownSegments}{Optional @data.frame specifying # \emph{non-overlapping} known segments. These segments must # not share loci. See @see "findLargeGaps" and @see "gapsToSegments".} # \item{seed}{An (optional) @integer specifying the random seed to be # set before calling the segmentation method. The random seed is # set to its original state when exiting. If @NULL, it is not set.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a @see "CBS" object. # } # # \details{ # Internally @see "DNAcopy::segment" of \pkg{DNAcopy} is used to # segment the signals. # This segmentation method support weighted segmentation. # } # # \section{Reproducibility}{ # The \code{DNAcopy::segment()} implementation of CBS uses approximation # through random sampling for some estimates. Because of this, # repeated calls using the same signals may result in slightly # different results, unless the random seed is set/fixed. # } # # \section{Missing and non-finite values}{ # Signals may contain missing values (@NA or @NaN), but not # infinite values (+/-@Inf). Loci with missing-value signals # are preserved and keep in the result. # # Likewise, genomic positions may contain missing values. # However, if they do, such loci are silently excluded before # performing the segmentation, and are not kept in the results. # The mapping between the input locus-level data and ditto of # the result can be inferred from the \code{index} column of # the locus-level data of the result. # # None of the input data may have infinite values, # i.e. -@Inf or +@Inf. If so, an informative error is thrown. # } # # \examples{ # @include "../incl/segmentByCBS.Rex" # @include "../incl/segmentByCBS,plot.Rex" # @include "../incl/segmentByCBS,tests.Rex" # } # # @author "HB" # # \references{ # [1] @include "../incl/OlshenVenkatraman_2004.Rd" \cr # [2] @include "../incl/VenkatramanOlshen_2007.Rd" \cr # } # # \seealso{ # To segment allele-specific tumor copy-number signals from a tumor # \emph{with} a matched normal, see @see "segmentByPairedPSCBS". # For the same \emph{without} a matched normal, # see @see "segmentByNonPairedPSCBS". # # It is also possible to prune change points after segmentation (with # identical results) using # \code{\link[PSCBS:pruneBySdUndo.CBS]{pruneBySdUndo}()}. # } # @keyword IO #*/########################################################################### setMethodS3("segmentByCBS", "default", function(y, chromosome=0L, x=NULL, index=seq_along(y), w=NULL, undo=0, avg=c("mean", "median"), ..., joinSegments=TRUE, knownSegments=NULL, seed=NULL, verbose=FALSE) { R_SANITY_CHECK <- TRUE # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # DNAcopy::getbdry() is slow for now default settings. Below we # implement a memoized version of this function. getbdry2 <- function(eta, nperm, alpha, tol=0.01, verbose=FALSE) { # Explictly setup cache root here, since it's only done by 'R.cache' # if that package is attached. Here we only load it. /HB 2013-09-27 .setupCacheRootPath() key <- list(method="segmentByCBS", eta=eta, nperm=as.integer(nperm), alpha=alpha, tol=tol, version="0.16.1") dirs <- c("PSCBS", "segmentByCBS", "sbdry") bdry <- loadCache(key=key, dirs=dirs) if (!is.null(bdry)) return(bdry) max.ones <- floor(nperm * alpha) + 1L bdry <- getbdry(eta=eta, nperm=nperm, max.ones=max.ones, tol=tol) saveCache(bdry, key=key, dirs=dirs) bdry } # getbdry2() # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'y': disallow <- c("Inf") y <- Arguments$getDoubles(y, disallow=disallow) nbrOfLoci <- length(y) length2 <- rep(nbrOfLoci, times=2) # Argument 'chromosome': if (is.null(chromosome)) { chromosome <- 0L } else { disallow <- c("Inf") chromosome <- Arguments$getIntegers(chromosome, range=c(0,Inf), disallow=disallow) if (length(chromosome) > 1) { chromosome <- Arguments$getIntegers(chromosome, length=length2, disallow=disallow) ## # If 'chromosome' is a vector of length J, then it must contain ## # a unique chromosome. ## chromosomes <- sort(unique(chromosome)) ## if (length(chromosomes) > 1) { ## stop("Argument 'chromosome' specifies more than one unique chromosome: ", paste(seqToHumanReadable(chromosomes), collapse=", ")) ## } ## chromosome <- chromosomes } } # For future usage chrom <- rep(chromosome, length.out=nbrOfLoci) # Argument 'x': if (is.null(x)) { x <- seq_len(nbrOfLoci) } else { disallow <- c("Inf") x <- Arguments$getDoubles(x, length=length2, disallow=disallow) } # Argument 'index': if (is.null(index)) { index <- seq_along(y) } else { index <- Arguments$getIndices(index) } # Argument 'w': hasWeights <- !is.null(w) if (hasWeights) { disallow <- c("NA", "NaN", "Inf") w <- Arguments$getDoubles(w, range=c(0,1), length=length2, disallow=disallow) } # Argument 'undo': undo <- Arguments$getDouble(undo, range=c(0,Inf)) # Argument 'avg': avg <- match.arg(avg) # Argument 'cpFlavor': joinSegments <- Arguments$getLogical(joinSegments) # Argument 'knownSegments': if (is.null(knownSegments)) { knownSegments <- data.frame(chromosome=integer(0), start=integer(0), end=integer(0)) } else { # if (!joinSegments) { # stop("Argument 'knownSegments' should only be specified if argument 'joinSegments' is TRUE.") # } } if (!is.data.frame(knownSegments)) { stop("Argument 'knownSegments' is not a data.frame: ", class(knownSegments)[1]) } if (!all(is.element(c("chromosome", "start", "end"), colnames(knownSegments)))) { stop("Argument 'knownSegments' does not have the required column names: ", hpaste(colnames(knownSegments))) } # Detailed validation of 'knownSegments'. for (chr in sort(unique(knownSegments$chromosome))) { dd <- subset(knownSegments, chromosome == chr) # Order segments by 'start'. o <- order(dd$start) dd <- dd[o,] # Known segments must not share 'start' or 'end' loci for (field in c("start", "end")) { xs <- dd[[field]] xs <- xs[!is.na(xs)] if (anyDuplicated(xs) > 0) { print(knownSegments) stop(sprintf("Detected segments on chromosome %s with non-unique '%s' positions in argument 'knownSegments'", chr, field)) } } # for (field ...) # Known segments must not overlap if (!all(dd$start[-1] >= dd$end[-nrow(dd)], na.rm=TRUE)) { print(knownSegments) stop("Detected overlapping segments on chromosome ", chr, " in argument 'knownSegments'.") } } # Argument 'seed': if (!is.null(seed)) { seed <- Arguments$getIntegers(seed) } # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Segmenting by CBS") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Setup up data", level=-10) data <- data.frame(chrom=chrom, x=x, y=y, index=index) if (hasWeights) { verbose && cat(verbose, "Adding locus-specific weights", level=-10) data$w <- w } verbose && str(verbose, data, level=-10) # Not needed anymore chrom <- x <- index <- y <- w <- NULL verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop data points without known genomic positions, because that # is what DNAcopy::CNA() will do otherwise. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ok <- (!is.na(data$chrom) & !is.na(data$x)) if (any(!ok)) { verbose && enter(verbose, "Dropping loci with unknown locations", level=-10) verbose && cat(verbose, "Number of loci dropped: ", sum(!ok), level=-10) data <- data[ok,,drop=FALSE] verbose && exit(verbose) } ok <- NULL # Not needed anymore # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Reorder data points along the genome, because that is what # DNAcopy::segment() will return. At the end, we will undo # the sort such that the returned 'data' object is always in # the same order and number of loci as the input data. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Ordering data along genome", level=-50) o <- order(data$chrom, data$x, decreasing=FALSE, na.last=TRUE) # Any change? if (any(o != seq_along(o))) { data <- data[o,,drop=FALSE] } o <- NULL # Not needed anymore verbose && str(verbose, data, level=-50) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multiple chromosomes? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify all chromosomes, excluding missing values chromosomes <- sort(unique(data$chrom), na.last=NA) nbrOfChromosomes <- length(chromosomes) if (nbrOfChromosomes > 1) { verbose && enter(verbose, "Segmenting multiple chromosomes") verbose && cat(verbose, "Number of chromosomes: ", nbrOfChromosomes) # Generate random seeds? seeds <- NULL if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=c(%s), kind=\"L'Ecuyer-CMRG\")\n", paste(seed, collapse=", ")) seeds <- randomSeed("advance", n=nbrOfChromosomes) verbose && printf(verbose, "Produced %d seeds from this stream for future usage\n", length(seeds)) } fitList <- list() for (kk in seq_len(nbrOfChromosomes)) { chromosomeKK <- chromosomes[kk] chrTag <- sprintf("Chr%02d", chromosomeKK) verbose && enter(verbose, sprintf("Chromosome #%d ('%s') of %d", kk, chrTag, nbrOfChromosomes)) seedKK <- seeds[[kk]] # Extract subset of data and parameters for this chromosome dataKK <- subset(data, chrom == chromosomeKK) verbose && str(verbose, dataKK, level=-10) chrom <- x <- index <- y <- w <- NULL fields <- attachLocally(dataKK, fields=c("chrom", "x", "index", "y", "w")) dataKK <- NULL # Not needed anymore knownSegmentsKK <- NULL if (!is.null(knownSegments)) { knownSegmentsKK <- subset(knownSegments, chromosome == chromosomeKK) if (nrow(knownSegmentsKK) == 0L) { knownSegmentsKK <- data.frame(chromosome=chromosomeKK, start=-Inf, end=+Inf) } verbose && cat(verbose, "Known segments:", level=-5) verbose && print(verbose, knownSegmentsKK, level=-5) } fitList[[chrTag]] <- future({ fit <- segmentByCBS(y=y, chromosome=chrom, x=x, w=w, index=index, undo=undo, avg=avg, joinSegments=joinSegments, knownSegments=knownSegmentsKK, ..., seed=seedKK, verbose=verbose) # Sanity checks if (R_SANITY_CHECK) { if (nrow(knownSegmentsKK) == 0) { # Since all missing data have been dropped... .stop_if_not(nrow(fit$data) == length(y)) # ...and ordered along the genome already. .stop_if_not(all.equal(fit$data$y, y)) } # Assert weights were used .stop_if_not(!hasWeights || !is.null(fit$data$w)) } # if (R_SANITY_CHECK) verbose && print(verbose, head(as.data.frame(fit)), level=-10) verbose && print(verbose, tail(as.data.frame(fit)), level=-10) fit }, seed = TRUE, label = sprintf("segmentByCBS-%s", chrTag)) rm(list=fields) # Not needed anymore verbose && exit(verbose) } # for (kk ...) verbose && enter(verbose, "Merging (independently) segmented chromosome", level=-50) fitList <- value(fitList) ## former Reduce() w/ append(..., addSplit = TRUE) fit <- do.call(c, args = c(fitList, addSplit = TRUE)) # Not needed anymore fitList <- NULL # Update parameters that otherwise may be incorrect fit$params$seed <- seed verbose && str(verbose, fit, level=-10) verbose && exit(verbose) segs <- as.data.frame(fit) if (nrow(segs) < 6) { verbose && print(verbose, segs, level=-10) } else { verbose && print(verbose, head(segs), level=-10) verbose && print(verbose, tail(segs), level=-10) } verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - return(fit) } # if (nbrOfChromosomes > 1) verbose && cat(verbose, "Chromosome: ", data$chrom[1L]) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subset 'knownSegments' # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Keeping only current chromosome for 'knownSegments'", level=-10) # Assume no missing values currChromosome <- data$chrom[1] verbose && cat(verbose, "Chromosome: ", currChromosome, level=-10) knownSegments <- subset(knownSegments, chromosome == currChromosome) if (nrow(knownSegments) == 0L) { knownSegments <- data.frame(chromosome=currChromosome, start=-Inf, end=+Inf) } nbrOfSegments <- nrow(knownSegments) verbose && cat(verbose, "Known segments for this chromosome:", level=-10) verbose && print(verbose, knownSegments, level=-10) verbose && exit(verbose) # Sanity checks if (R_SANITY_CHECK) { # Here 'knownSegments' should specify at most a single chromosome uChromosomes <- sort(unique(knownSegments$chromosome)) if (length(uChromosomes) > 1) { stop("INTERNAL ERROR: Argument 'knownSegments' specifies more than one chromosome: ", hpaste(uChromosomes)) } } # if (R_SANITY_CHECK) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multiple segments? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity check of limitation /HB 2011-10-19 if (nbrOfSegments > 1) { verbose && enter(verbose, "Segmenting multiple segments on current chromosome", level=-5) verbose && cat(verbose, "Number of segments: ", nbrOfSegments, level=-5) # Create a splitter-only CBS object dataS <- data.frame(y=c(0,0), chromosome=c(1,2), x=c(0,0)) if (hasWeights) dataS$w <- 1 splitter <- segmentByCBS(dataS) dataS <- NULL suppressWarnings({ splitter <- extractSegment(splitter, 2) # Sanity check if (R_SANITY_CHECK) { .stop_if_not(nbrOfSegments(splitter, splitters=TRUE) == 1) } # if (R_SANITY_CHECK) }) # Generate random seeds? seeds <- NULL if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=c(%s), kind=\"L'Ecuyer-CMRG\")\n", paste(seed, collapse=", ")) seeds <- randomSeed("advance", n=nbrOfSegments) verbose && printf(verbose, "Produced %d seeds from this stream for future usage\n", length(seeds)) } fitList <- list() for (jj in seq_len(nbrOfSegments)) { seg <- knownSegments[jj,] chromosomeJJ <- seg$chromosome xStart <- seg$start xEnd <- seg$end segTag <- sprintf("chr%s:(%s,%s)", chromosomeJJ, xStart, xEnd) verbose && enter(verbose, sprintf("Segment #%d ('%s') of %d", jj, segTag, nbrOfSegments), level=-10) ## Nothing to do? isSplitter <- (is.na(xStart) && is.na(xEnd)) if (isSplitter) { fit <- splitter verbose && cat(verbose, "Nothing to segment. Inserting an explicit splitter.", level=-10) fitList[[segTag]] <- fit fit <- NULL verbose && exit(verbose) next } # Extract subset of data and parameters for this segment dataJJ <- subset(data, chrom == chromosomeJJ & xStart <= x & x <= xEnd) verbose && str(verbose, dataJJ, level=-50) chrom <- x <- index <- y <- w <- NULL fields <- attachLocally(dataJJ, fields=c("chrom", "x", "index", "y", "w")) dataJJ <- NULL # Not needed anymore nbrOfLoci <- length(y) # Empty segment? # [AD HOC. Should be done by segmentCBS(). /HB 2011-10-21] if(nbrOfLoci == 0) { fit <- splitter fit$output$chromosome <- chromosomeJJ fit$output$start <- xStart fit$output$end <- xEnd fit$output$nbrOfLoci <- nbrOfLoci fitList[[segTag]] <- fit fit <- NULL verbose && exit(verbose) next } seedJJ <- seeds[[jj]] fitList[[segTag]] <- future({ fit <- segmentByCBS(y=y, chromosome=chrom, x=x, w=w, index=index, undo=undo, avg=avg, joinSegments=joinSegments, knownSegments=seg, ..., seed=seedJJ, verbose=less(verbose,1)) # Sanity checks if (R_SANITY_CHECK) { .stop_if_not(nrow(fit$data) == nbrOfLoci) .stop_if_not(all.equal(fit$data$y, y)) # Assert weights were used .stop_if_not(!hasWeights || !is.null(fit$data$w)) } # if (R_SANITY_CHECK) segs <- as.data.frame(fit) if (nrow(segs) < 6) { verbose && print(verbose, segs, level=-10) } else { verbose && print(verbose, head(segs), level=-10) verbose && print(verbose, tail(segs), level=-10) } # Sanity check if (R_SANITY_CHECK) { ## NOTE: Need to use PSCBS::nbrOfSegments() for this to work ## when 'PSCBS' is not attached. The reason is that the future ## picks up the local integer variable 'nbrOfSegments' instead ## of the nbrOfSegments() function of 'PSCBS' as a global ## variable. ## https://github.com/HenrikBengtsson/PSCBS/issues/67 .stop_if_not(TRUE && PSCBS::nbrOfSegments(fit, splitters=TRUE) > 0) } # if (R_SANITY_CHECK) fit }, seed = TRUE, label = sprintf("segmentByCBS-%s", segTag)) rm(list=fields) # Not needed anymore verbose && exit(verbose) } # for (jj ...) verbose && enter(verbose, "Merging (independently) segmented known segments", level=-10) verbose && cat(verbose, "Number of segments: ", length(fitList), level=-10) fitList <- value(fitList) verbose && str(verbose, fitList, level=-50) ## former Reduce() w/ append(..., addSplit = FALSE) fit <- do.call(c, args = c(fitList, addSplit = FALSE)) # Not needed anymore fitList <- NULL # Update parameters that otherwise may be incorrect fit$params$seed <- seed verbose && str(verbose, fit, level=-10) verbose && exit(verbose) segs <- getSegments(fit) if (nrow(segs) > 6) { verbose && print(verbose, head(segs), level=-10) verbose && print(verbose, tail(segs), level=-10) } else { verbose && print(verbose, segs, level=-10) } # Sanity checks if (R_SANITY_CHECK) { segs <- getSegments(fit) .stop_if_not(all(segs$start[-1] >= segs$end[-nrow(segs)], na.rm=TRUE)) .stop_if_not(all(diff(segs$start) >= 0, na.rm=TRUE)) ## FIXME: > 0 .stop_if_not(all(diff(segs$end) >= 0, na.rm=TRUE)) ## FIXME: > 0 # if (nrow(fit$data) != length(y)) { # print(c(nrow(fit$data), nrow(data))) # } # .stop_if_not(nrow(fit$data) == nrow(data)) # .stop_if_not(all(fit$data$chromosome == data$chromosome)) # .stop_if_not(all(fit$data$x == data$x)) # .stop_if_not(all(fit$data$index == data$index)) # .stop_if_not(all.equal(fit$data$y, data$y)) } # if (R_SANITY_CHECK) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Return results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - return(fit) } # if (nbrOfSegments > 1) nbrOfSegments <- nrow(knownSegments) # Sanity check if (R_SANITY_CHECK) { .stop_if_not(nbrOfSegments <= 1) } # if (R_SANITY_CHECK) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Specific segment? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (nbrOfSegments > 0) { knownSegments <- subset(knownSegments, chromosome == chromosome) nbrOfSegments <- nrow(knownSegments) # Sanity check if (R_SANITY_CHECK) { .stop_if_not(nbrOfSegments <= 1) } # if (R_SANITY_CHECK) } if (nbrOfSegments == 1) { seg <- knownSegments[1,] chromosomeJJ <- seg$chromosome xStart <- seg$start xEnd <- seg$end segTag <- sprintf("chr%s:(%s,%s)", chromosomeJJ, xStart, xEnd) verbose && printf(verbose, "Extracting segment '%s'", segTag, level=-50) # Extract subset of data and parameters for this segment data <- subset(data, chrom == chromosomeJJ & xStart <= x & x <= xEnd) verbose && str(verbose, data, level=-50) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Retrieving segmentation function # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Retrieving the fit function", level=-50) # We need to attach the 'DNAcopy' package pkgName <- "DNAcopy" use(pkgName) pkg <- packageDescription(pkgName) pkgVer <- pkg$Version pkgDetails <- sprintf("%s v%s", pkgName, pkgVer) methodName <- "segment" verbose && cat(verbose, "Method: ", methodName, level=-50) verbose && cat(verbose, "Package: ", pkgDetails, level=-50) # Get the fit function for the segmentation method # fitFcn <- getExportedValue(pkgName, methodName) fitFcn <- getFromNamespace(methodName, pkgName) verbose && str(verbose, "Function: ", fitFcn, level=-50) formals <- formals(fitFcn) verbose && cat(verbose, "Formals:", level=-50) verbose && str(verbose, formals, level=-50) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setting up arguments to pass to segmentation function # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Setting up method arguments", level=-50) verbose && enter(verbose, "Setting up ", pkgName, " data structure", level=-50) sampleName <- "y" # This is going to be the name of the data field # Supress all warnings, in order to avoid warnings by DNAcopy::CNA() # on "array has repeated maploc positions". Ideally we should filter # just those out. /HB 2013-10-22 suppressWarnings({ cnData <- CNA( genomdat = data$y, chrom = data$chrom, data.type = "logratio", maploc = data$x, sampleid = sampleName, presorted = TRUE ) }) verbose && str(verbose, cnData, level=-50) names(cnData)[3] <- sampleName verbose && str(verbose, cnData, level=-50) verbose && exit(verbose) # Sanity check if (R_SANITY_CHECK) { # (because all loci with unknown locations have already been dropped) .stop_if_not(nrow(cnData) == nrow(data)) } # if (R_SANITY_CHECK) userArgs <- list(...) if (length(userArgs) > 0) { verbose && cat(verbose, "User arguments:", level=-50) verbose && str(verbose, userArgs, level=-50) } # Check if 'sbdry' can/should be precalculated. This uses memoization # so that next time you segment with same 'nperm', 'alpha' and 'eta' # parameters, there will be much less startup overhead. if (length(userArgs) > 0 && !is.element("sbdry", names(userArgs))) { keys <- c("nperm", "alpha", "eta") keep <- is.element(keys, names(userArgs)) if (any(keep)) { verbose && enter(verbose, "Precalculating argument 'sbdry' (with memoization)", level=-50) # Precalculate boundaries argsT <- formals[keys] keys <- keys[keep] argsT[keys] <- userArgs[keys] argsT$verbose <- less(verbose, 5) sbdry <- do.call(getbdry2, args=argsT) userArgs$sbdry <- sbdry verbose && exit(verbose) } } params <- list() if (hasWeights) { params$weights <- data$w } if (undo > 0) { params$undo.splits <- "sdundo" params$undo.SD <- undo } verbose && cat(verbose, "Segmentation parameters:", level=-50) verbose && str(verbose, params, level=-50) # Assign/overwrite by user arguments if (length(userArgs) > 0) { for (ff in names(userArgs)) { params[[ff]] <- userArgs[[ff]] } } verbose && cat(verbose, "Segmentation and user parameters:", level=-50) verbose && str(verbose, params, level=-50) # Cleaning out unknown parameters keep <- (names(params) %in% names(formals)) params <- params[keep] args <- c(list(cnData), params, verbose=as.logical(verbose)) verbose && cat(verbose, "Final arguments:", level=-50) verbose && str(verbose, args, level=-50) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segmentation function # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, sprintf("Calling %s() of %s", methodName, pkgName), level=-50) # There are a few cases where we can/need to do a dummy segmentation # based on a single data points: # (a) WORKAROUND for the case when there are no data points. # (b) SPEEDUP: When undo=+Inf we don't really have to segment. nbrOfNonMissingLoci <- sum(!is.na(cnData$y)) if (nbrOfNonMissingLoci == 0) { args[[1]] <- CNA(genomdat=0, chrom=0, maploc=0) if (hasWeights) args$weights <- 1.0 } else if (undo == +Inf) { args[[1]] <- CNA(genomdat=0, chrom=0, maploc=0) if (hasWeights) args$weights <- 1.0 verbose && cat(verbose, "Skipping identification of new change points (undo=+Inf)", level=-50) } ## Set random seed? if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=c(%s), kind=\"L'Ecuyer-CMRG\")\n", paste(seed, collapse=", ")) } # In case the method writes to stdout, we capture it # Note: DNAcopy::segment() *does* this. stdout <- capture.output({ # Does not work, because some internal function of the fit function # may only be accessible from within the namespace # How to do this for DNAcopy::segment()? /HB ## fit <- do.call(fitFcn, args) # This works, but requires that one loads the package and that the # function is not masked in the search() path. t <- system.time({ fit <- do.call(methodName, args) }, gcFirst = FALSE) # Drop the 'call' (because it will be huge due to the do.call() call) fit$call <- NULL }) attr(fit, "processingTime") <- t attr(fit, "pkgDetails") <- pkgDetails attr(fit, "randomSeed") <- seed # WORKAROUND for the case when there are no data points. if (nbrOfNonMissingLoci == 0) { # Drop dummy data point... fit$data <- cnData ## fit$data[-1,,drop=FALSE] # ...dummy region found output <- fit$output segRows <- fit$segRows # Sanity check if (R_SANITY_CHECK) { .stop_if_not(nrow(output) == 1) } # if (R_SANITY_CHECK) # Was a region specified? if (nbrOfSegments == 1) { seg <- knownSegments[1,] output$ID <- sampleName output$chrom <- seg$chromosome if (is.finite(seg$start)) { output$loc.start <- seg$start } if (is.finite(seg$end)) { output$loc.end <- seg$end } output$num.mark <- 0L output$seg.mean <- NA_real_ segRows[1,] <- NA_integer_ } else { output <- output[-1,,drop=FALSE] segRows <- segRows[-1,,drop=FALSE] } fit$output <- output fit$segRows <- segRows } else if (undo == +Inf) { # Drop dummy data point... fit$data <- cnData ## fit$data[-1,,drop=FALSE] # ...dummy region found output <- fit$output segRows <- fit$segRows # Sanity check if (R_SANITY_CHECK) { .stop_if_not(nrow(output) == 1) } # if (R_SANITY_CHECK) # Was a region specified? if (nbrOfSegments == 1) { seg <- knownSegments[1,] output$ID <- sampleName output$chrom <- seg$chromosome if (is.finite(seg$start)) { output$loc.start <- seg$start } else { output$loc.start <- min(cnData$maploc, na.rm=TRUE) } if (is.finite(seg$end)) { output$loc.end <- seg$end } else { output$loc.end <- max(cnData$maploc, na.rm=TRUE) } } output$num.mark <- nrow(fit$data) output$seg.mean <- mean(fit$data$y, na.rm=TRUE) segRows$endRow <- nrow(fit$data) fit$output <- output fit$segRows <- segRows } # if (undo == +Inf) verbose && cat(verbose, "Captured output that was sent to stdout:", level=-50) stdout <- paste(stdout, collapse="\n") verbose && cat(verbose, stdout, level=-50) verbose && cat(verbose, "Fitting time (in seconds):", level=-50) verbose && print(verbose, t, level=-50) verbose && cat(verbose, "Fitting time per 1000 loci (in seconds):", level=-50) verbose && print(verbose, 1000*t/nbrOfLoci, level=-50) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Restructure # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Restructuring results", level=-50) # Coerce fit$output$num.mark <- as.integer(fit$output$num.mark) # Coerce 'chrom' to a plain integer fit$data$chrom <- unclass(fit$data$chrom) # Store genomewide index fit$data$index <- data$index # Store weights fit$data$w <- data$w # Not needed anymore data <- NULL verbose && exit(verbose) # Store also interesting parameters to DNAcopy::segment() keys <- setdiff(names(formals), c("x", "weights", "sbdry", "verbose")) keys <- c(keys, "undo", "seed") keep <- is.element(names(params), keys) keep <- names(params)[keep] params <- params[keep] params$undo <- undo params$joinSegments <- joinSegments params$knownSegments <- knownSegments params$seed <- seed fit$params <- params # class(fit) <- c("CBS", class(fit)) class(fit) <- c("CBS", "AbstractCBS") # Sanity checks if (R_SANITY_CHECK) { segRows <- fit$segRows .stop_if_not(all(segRows[,1] <= segRows[,2], na.rm=TRUE)) .stop_if_not(all(segRows[-nrow(segRows),2] < segRows[-1,1], na.rm=TRUE)) } # if (R_SANITY_CHECK) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Renaming column names # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) names <- colnames(data) names <- gsub("chrom", "chromosome", names, fixed=TRUE) names <- gsub("maploc", "x", names, fixed=TRUE) colnames(data) <- names # Drop 'CNA' class and DNAcopy attributes class(data) <- c("data.frame") attr(data, "data.type") <- NULL fit$data <- data segs <- fit$output names <- colnames(segs) names <- gsub("ID", "sampleName", names, fixed=TRUE) names <- gsub("seg.mean", "mean", names, fixed=TRUE) names <- gsub("chrom", "chromosome", names, fixed=TRUE) names <- gsub("num.mark", "nbrOfLoci", names, fixed=TRUE) names <- gsub("loc.", "", names, fixed=TRUE) # loc.start, loc.end colnames(segs) <- names fit$output <- segs # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Join segments? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (joinSegments) { if (nbrOfSegments == 1) { starts <- knownSegments$start ends <- knownSegments$end if (is.infinite(starts)) starts <- segs$start if (is.infinite(ends)) ends <- segs$end range <- range(c(starts, ends), na.rm=TRUE) } else { range <- NULL } fit <- joinSegments(fit, range=range, verbose=less(verbose, 10)) # Sanity checks if (R_SANITY_CHECK) { segRows <- fit$segRows .stop_if_not(all(segRows[,1] <= segRows[,2], na.rm=TRUE)) .stop_if_not(all(segRows[-nrow(segRows),2] < segRows[-1,1], na.rm=TRUE)) } # if (R_SANITY_CHECK) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Update? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (avg != "mean") { verbose && enter(verbose, "Updating mean level using different estimator") verbose && cat(verbose, "Estimator: ", avg) fit <- updateMeans(fit, avg=avg, verbose=less(verbose, 20)) verbose && exit(verbose) } verbose && cat(verbose, "Results object:", level=-10) verbose && str(verbose, fit, level=-10) verbose && exit(verbose) verbose && exit(verbose) fit }) # segmentByCBS() setMethodS3("segmentByCBS", "data.frame", function(y, ...) { # To please R CMD check data <- y y <- data$y if (is.null(y)) { y <- data$cn if (is.null(y)) { y <- data$CT } } segmentByCBS(y=y, chromosome=data$chromosome, x=data$x, index=data$index, w=data$w, ...) }) setMethodS3("segmentByCBS", "CBS", function(...) { resegment(...) }) # segmentByCBS() PSCBS/R/PairedPSCBS.unTumorBoost.R0000644000176200001440000000361214564051545016141 0ustar liggesusers# @title "Re-calculates the segmented profile using non-TumorBoost BAFs" setMethodS3("unTumorBoost", "PairedPSCBS", function(fit, ..., verbose=FALSE) { # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enterf(verbose, "Relcalculating %s profile without TumorBoost", class(fit)[1L]) # Nothing to do? if (!fit$params$tbn) { verbose && cat(verbose, "Profile is not from TumorBoost signals. Skipping.") verbose && exit(verbose) return(fit) } verbose && enter(verbose, "Updating locus-level data") data <- getLocusData(fit) data$betaTN <- data$betaT isHet <- !is.na(data$rho) data$rho[isHet] <- 2*abs(data$betaTN[isHet]-1/2) fit$data <- data verbose && exit(verbose) verbose && enter(verbose, "Updating segments") segs <- getSegments(fit) segs$abCall <- NULL segs$lohCall <- NULL fit$output <- segs verbose && exit(verbose) verbose && enter(verbose, "Updating parameters") params <- fit$params params$tbn <- FALSE params$deltaAB <- params$alphaAB <- NULL params$deltaLowC1 <- params$alphaLowC1 <- NULL fit$params <- params verbose && exit(verbose) verbose && enter(verbose, "Resetting miscellaneous parameters and estimates") fit$changepoints <- NULL fit$deshearC1C2 <- NULL fit$cScaled <- NULL fit$kappa <- NULL fit$scale <- NULL fit <- clearBootstrapSummaries(fit, verbose=less(verbose, 50)) verbose && exit(verbose) verbose && enter(verbose, "Update segment levels") fit <- updateMeans(fit, verbose=less(verbose, 50)) verbose && exit(verbose) verbose && exit(verbose) fit }, protected=TRUE) # unTumorBoost() ############################################################################## # HISTORY # 2014-03-28 # o Added unTumorBoost() for PairedPSCBS. ############################################################################## PSCBS/R/PairedPSCBS.CALL.R0000644000176200001440000001321414564051545014173 0ustar liggesuserssetMethodS3("callABandHighAI", "PairedPSCBS", function(fit, deltaAB=estimateDeltaAB(fit), alphaAB=0.05, deltaHighAI=0.60, alphaHighAI=0.05, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments to be in allelic balance (AB) or extreme allelic imbalance (AI)") # Calculate DH confidence intervals, if not already done probs <- sort(unique(c(alphaAB, alphaHighAI))) probs <- sort(unique(c(probs, 1-probs))) fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) # Call allelic balance fit <- callAllelicBalanceByDH(fit, delta=deltaAB, alpha=alphaAB, ..., verbose=less(verbose, 1)) # Call high allelic imbalance fit <- callExtremeAllelicImbalanceByDH(fit, delta=deltaHighAI, alpha=alphaHighAI, ..., verbose=less(verbose, 1)) verbose && exit(verbose) fit }, private=TRUE) # callABandHighAI() setMethodS3("callABandLowC1", "PairedPSCBS", function(fit, deltaAB=estimateDeltaAB(fit), alphaAB=0.05, deltaLowC1=0.50, alphaLowC1=0.05, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments to be in allelic balance (AB) or low minor copy number (low C1)") # Calculate DH confidence intervals, if not already done probs <- sort(unique(c(alphaAB, alphaLowC1))) probs <- sort(unique(c(probs, 1-probs))) fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) # Call allelic balance fit <- callAllelicBalanceByDH(fit, delta=deltaAB, alpha=alphaAB, ..., verbose=less(verbose, 1)) # Call high allelic imbalance fit <- callLowC1ByC1(fit, delta=deltaLowC1, alpha=alphaLowC1, ..., verbose=less(verbose, 1)) verbose && exit(verbose) fit }, private=TRUE) # callABandLowC1() setMethodS3("extractCallsByLocus", "PairedPSCBS", function(fit, ...) { # Extract locus data data <- getLocusData(fit, ...) nbrOfLoci <- nrow(data) # Extract segment data segs <- getSegments(fit, splitters=TRUE) # Identify segment calls callCols <- grep("Call$", colnames(segs)) nbrOfCalls <- length(callCols) chromosome <- data$chromosome x <- data$x y <- data[,3] # Allocate locus calls naValue <- NA callsL <- matrix(naValue, nrow=nbrOfLoci, ncol=nbrOfCalls) colnames(callsL) <- colnames(segs)[callCols] callsL <- as.data.frame(callsL) # For each segment... for (ss in seq_len(nrow(segs))) { seg <- segs[ss,] idxs <- which(chromosome == seg$chromosome & seg$tcnStart <= x & x <= seg$tcnEnd) idxs <- Arguments$getIndices(idxs, max=nbrOfLoci) # Sanity check ## .stop_if_not(length(idxs) == seg$tcnNbrOfLoci) callsSS <- seg[callCols] for (cc in seq_len(nbrOfCalls)) { callsL[idxs,cc] <- callsSS[,cc] } } # for (ss ...) # The calls for loci that have missing annotations or observations, # should also be missing, i.e. NA. nok <- (is.na(chromosome) | is.na(x) | is.na(y)) callsL[nok,] <- NA # Sanity check .stop_if_not(nrow(callsL) == nbrOfLoci) .stop_if_not(ncol(callsL) == nbrOfCalls) callsL }, private=TRUE) # extractCallsByLocus() ############################################################################## # HISTORY # 2013-03-22 # o Added extractCallsByLocus() for PairedPSCBS. # 2011-06-14 # o Updated code to recognize new column names. # 2011-05-29 # o Renamed all arguments, variables, function named 'tau' to 'delta'. # 2011-02-03 # o Updated default for 'tauAB' of callABandHighAI() and callABandLowC1() # to be estimated from data using estimateTauAB(). # 2010-12-07 # o Added callLowC1ByC1() and callABandLowC1(). # 2010-11-27 # o Corrected verbose output to call results. # 2010-11-26 [HB] # o Now all call functions estimate symmetric bootstrap quantiles for # convenince of plotting confidence intervals. # o BUG FIX: callABandHighAI() for PairedPSCBS used the old DH-only # bootstrap method. # o BUG FIX: The call functions, for instance callABandHighAI(), would throw # 'Error in quantile.default(x, probs = alpha) : missing values and NaN's # not allowed if 'na.rm' is FALSE' unless bootstrapTCNandDHByRegion() was # run before. # 2010-11-22 [HB] # o Added more verbose output to callABandHighAI(). # o Updated callAllelicBalanceByDH() and callExtremeAllelicImbalanceByDH() # to utilize bootstrapTCNandDHByRegion(). # 2010-10-25 [HB] # o Relaced argument 'ciRange' with 'alpha' for callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH(). # o Renamed callAllelicBalance() to callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH() to callExtremeAllelicImbalance(). # o Added arguments 'alphaAB' and 'alphaHighAI' to callABandHighAI(). # o Added sanity checks to the call methods. # o Now arguments '...' to callABandHighAI() are passed down. # o Now also arguments '...' to callAllelicBalance() and # callExtremeAllelicImbalance() are passed to bootstrapDHByRegion(). # o Added argument 'ciRange' to callAllelicBalance() and # callExtremeAllelicImbalance(). # 2010-09-16 [HB] # o Added callABandHighAI(). # o Added callAllelicBalance() and callExtremeAllelicImbalance(). # o Created. ############################################################################## PSCBS/R/AbstractCBS.RESTRUCT.R0000644000176200001440000003426514564202700015027 0ustar liggesusers###########################################################################/** # @set "class=AbstractCBS" # @RdocDocumentation "Restructuring AbstractCBS objects" # @alias RestructPSCBS # # \description{ # This page describes available methods for restructuring an # @see "AbstractCBS" object. # # \itemize{ # \item @seemethod "extractChromosomes" / # @seemethod "extractChromosome" # - Extracts an @see "AbstractCBS" with the specified chromosomes. # # \item @seemethod "extractSegments" / # @seemethod "extractSegment" # - Extracts an @see "AbstractCBS" with the specified segments. # # \item @seemethod "extractRegions" / # @seemethod "extractRegion" # - Extracts an @see "AbstractCBS" with the specified regions # each of a certain size, where a region is defined as a # connected set of segments. # # \item @seemethod "dropRegions" / # @seemethod "dropRegion" # - Drops specified regions and returns an @see "AbstractCBS" # without them. # # \item @seemethod "dropChangePoint" / # @seemethod "mergeTwoSegments" # - Drops a change point by merging two neighboring segments # and recalculates the statistics for the merged segment # before returning an @see "AbstractCBS". # # \item @seemethod "dropChangePoints" # - Drops zero or more change points # and recalculates the segment statistics # before returning an @see "AbstractCBS". # # \item @seemethod "mergeThreeSegments" # - Merges a segment with its two flanking segments # and recalculates the statistics for the merged segment # before returning an @see "AbstractCBS". # } # # All of the above methods are implemented for @see "CBS" and # @see "PairedPSCBS" objects. # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("renameChromosomes", "AbstractCBS", function(fit, from, to, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'from' & 'to': from <- Arguments$getIntegers(from, disallow=c("NaN", "Inf")) n <- length(from) to <- Arguments$getIntegers(to, disallow=c("NaN", "Inf"), length=c(n,n)) # Nothing to do? if (n == 0) { return(fit) } data <- getLocusData(fit) segs <- getSegments(fit, splitters=TRUE, simplify=FALSE) knownSegments <- fit$params$knownSegments for (cc in seq_len(n)) { chr <- from[cc] chrN <- to[cc] data$chromosome[data$chromosome == chr] <- chrN segs$chromosome[segs$chromosome == chr] <- chrN knownSegments$chromosome[knownSegments$chromosome == chr] <- chrN } # for (cc ...) fit <- setLocusData(fit, data) fit <- setSegments(fit, segs) fit$params$knownSegments <- knownSegments fit }, protected=TRUE) # renameChromosomes() setMethodS3("extractChromosomes", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("extractChromosome", "AbstractCBS", function(x, chromosome, ...) { # To please R CMD check this <- x # Argument 'chromosome': chromosome <- Arguments$getInteger(chromosome, disallow=c("NaN", "Inf")) extractChromosomes(this, chromosomes=chromosome, ...) }, protected=TRUE) setMethodS3("extractSegments", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("extractSegment", "AbstractCBS", function(this, idx, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'region': idx <- Arguments$getIndex(idx, max=nbrOfSegments(this, splitters=TRUE)) extractSegments(this, idxs=idx, ...) }, private=TRUE) # extractSegment() setMethodS3("extractRegions", "AbstractCBS", function(this, regions, H=1, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(this, splitters=TRUE) # Argument 'regions': regions <- Arguments$getIndices(regions, max=nbrOfSegments) # Argument 'H': H <- Arguments$getInteger(H, range=c(0,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Extract regions of a certain length") verbose && cat(verbose, "Left-most segments of regions to be extracted:") verbose && str(verbose, regions) verbose && cat(verbose, "Number of segments in each region: ", H) # Identify segments to keep Hs <- seq_len(H) regions <- regions - 1L regions <- as.list(regions) segments <- lapply(regions, FUN=function(region) region + Hs) segments <- unlist(segments, use.names=FALSE) segments <- sort(unique(segments)) verbose && cat(verbose, "Final set of segments to be extracted:") verbose && str(verbose, segments) res <- extractSegments(this, idxs=segments, ...) verbose && exit(verbose) res }, protected=TRUE) # extractRegions() setMethodS3("extractRegion", "AbstractCBS", function(this, region, ...) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'region': region <- Arguments$getIndex(region, max=nbrOfSegments(this, splitters=TRUE)) extractRegions(this, regions=region, ...) }, private=TRUE) # extractRegion() ###########################################################################/** # @RdocMethod mergeTwoSegments # @aliasmethod dropChangePoint # # @title "Merge two neighboring segments" # # \description{ # @get "title" into one segment, which is done by dropping their # common change point and recalculating the segment statistics. # } # # @synopsis # # \arguments{ # \item{...}{Not used.} # } # # \value{ # Returns an @see "AbstractCBS" of the same class with one less segment. # } # # @author "HB" # # \seealso{ # To merge a segment and its two flanking segments, see # @seemethod "mergeThreeSegments". # To drop regions (a connected set of segments) # see @seemethod "dropRegions". # @seeclass # } #*/########################################################################### setMethodS3("mergeTwoSegments", "AbstractCBS", abstract=TRUE, protected=TRUE) setMethodS3("dropChangePoint", "AbstractCBS", function(fit, idx, ...) { # Argument 'idx': ## max <- nbrOfChangePoints(fit, splitters=TRUE, ...) max <- nbrOfSegments(fit, splitters=TRUE, ...) - 1L idx <- Arguments$getIndex(idx, max=max) mergeTwoSegments(fit, left=idx, ...) }, protected=TRUE) ###########################################################################/** # @RdocMethod dropChangePoints # # @title "Drops zero or more change points" # # \description{ # @get "title", which is done by dropping one change point at the # time using @seemethod "dropChangePoint" # and recalculating the segment statistics at the end. # # \emph{NOTE: This method only works if there is only one chromosome.} # } # # @synopsis # # \arguments{ # \item{idxs}{An @integer @vector specifying the change points to be dropped.} # \item{update}{If @TRUE, segment statistics are updated.} # \item{...}{Other arguments passed to @seemethod "dropChangePoint" # and @seemethod "updateMeans".} # } # # \value{ # Returns an @see "AbstractCBS" of the same class with # \code{length(idxs)} segments. # } # # @author "HB" # # \seealso{ # @seeclass # } #*/########################################################################### setMethodS3("dropChangePoints", "AbstractCBS", function(fit, idxs, update=TRUE, ...) { # Assert that there is only one chromosome chrs <- getChromosomes(fit) if (length(chrs) > 1) { stop("dropChangePoints() only support single-chromosome data: ", hpaste(chrs)) } # Argument 'idxs': ## max <- nbrOfChangePoints(fit, splitters=TRUE, ...) max <- nbrOfSegments(fit, splitters=TRUE, ...) - 1L idxs <- Arguments$getIndices(idxs, max=max) # Drop change points one by one idxs <- unique(idxs) idxs <- sort(idxs, decreasing=TRUE) for (ii in seq_along(idxs)) { idx <- idxs[ii] updateI <- update && (ii == length(idxs)) fit <- dropChangePoint(fit, idx=idx, update=updateI, ...) } # Update segment statistics? if (update) { fit <- updateMeans(fit, ...) } fit }, protected=TRUE) ###########################################################################/** # @RdocMethod mergeThreeSegments # # @title "Merge a segment and its two flanking segments" # # \description{ # @get "title" into one segment, and recalculating the segment statistics. # } # # @synopsis # # \arguments{ # \item{middle}{An @integer specifying the three segments # (middle-1, middle, middle+1) to be merged.} # \item{...}{Additional arguments passed to @seemethod "mergeTwoSegments".} # } # # \value{ # Returns an @see "AbstractCBS" of the same class with two less segment. # } # # @author "HB" # # \seealso{ # Internally @seemethod "mergeTwoSegments" is used. # @seeclass # } #*/########################################################################### setMethodS3("mergeThreeSegments", "AbstractCBS", function(fit, middle, ...) { # Argument 'middle': S <- nbrOfSegments(fit, splitters=TRUE) middle <- Arguments$getIndex(middle, range=c(2L, S)) # Assert that the three segments are on the same chromosome idxs <- middle + c(-1L, 0L, +1L) fitT <- extractSegments(fit, idxs) chrs <- getChromosomes(fitT) if (length(chrs) != 1L) { stop("Argument 'middle' specifies a segment that is at the very end of a chromosome: ", middle) } fitT <- NULL # Not needed anymore fit <- mergeTwoSegments(fit, left=middle, ...) fit <- mergeTwoSegments(fit, left=middle-1L, ...) fit }) # mergeThreeSegments() ###########################################################################/** # @RdocMethod dropRegions # @aliasmethod dropRegion # # @title "Drops chromosomal regions (a connected set of segments)" # # \description{ # @get "title" each of a certain size (number of segments). # \emph{None of the statistics are recalculated}. # } # # @synopsis # # \arguments{ # \item{regions}{An @integer @vector of length R specifying the indices # of the left most segment in each of the R regions to be dropped.} # \item{H}{A non-negative @integer specifying the size of each region, # i.e. the number of segments per region.} # \item{...}{Additional arguments passed to @seemethod "extractRegions".} # \item{asMissing}{If @TRUE, dropped segments are replaced by missing values, # otherwise they are truly dropped.} # \item{verbose}{A @logical or a @see "R.utils::Verbose" object.} # } # # \value{ # Returns an @see "AbstractCBS" object of the same class with (at most) # R*H segments dropped. # If some regions overlap (share segments), then fewer than R*H segments # are dropped. # } # # @author "HB" # # \seealso{ # Internally @seemethod "extractRegions" is used. # See also @seemethod "dropChangePoint" and @seemethod "mergeTwoSegments". # @seeclass # } #*/########################################################################### setMethodS3("dropRegions", "AbstractCBS", function(this, regions, H=1, ..., asMissing=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nbrOfSegments(this, splitters=TRUE) # Argument 'regions': regions <- Arguments$getIndices(regions, max=nbrOfSegments) # Argument 'H': H <- Arguments$getInteger(H, range=c(0,Inf)) # Argument 'asMissing': asMissing <- Arguments$getLogical(asMissing) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Dropping regions of a certain length") verbose && cat(verbose, "Left-most segments of regions to be dropped:") verbose && str(verbose, regions) verbose && cat(verbose, "Number of segments in each region: ", H) # Nothing to do? if (H == 0) { verbose && cat(verbose, "Nothing to do. No segments will be dropped.") verbose && exit(verbose) return(this) } # Identify segments to drop Hs <- seq_len(H) regions <- regions - 1L regions <- as.list(regions) regions <- lapply(regions, FUN=function(region) region + Hs) regions <- unlist(regions, use.names=FALSE) regions <- sort(unique(regions)) verbose && cat(verbose, "Final set of segments to be dropped:") verbose && str(verbose, regions) # Identify segments to keep allRegions <- seq_len(nbrOfSegments) keepSegments <- setdiff(allRegions, regions) verbose && cat(verbose, "Final set of segments to be kept:") verbose && str(verbose, keepSegments) dropped <- extractRegions(this, regions=regions, ...) res <- this if (length(regions) > 0) { if (asMissing) { segs <- getSegments(res, splitters=TRUE) pattern <- "(chromosome|id|start|end)$" # TODO/AD HOC: Should be class specific /HB 2011-10-17 pattern <- "(chromosome|id)$" excl <- grep(pattern, colnames(segs), ignore.case=TRUE, invert=TRUE) segs[regions,excl] <- NA res$output <- segs # TODO/AD HOC: Should be class specific /HB 2011-10-17 for (ff in grep("segRows", names(res), ignore.case=TRUE, value=TRUE)) { res[[ff]][regions,] <- NA } } else { res <- extractRegions(res, regions=keepSegments, ...) } } res$dropped <- dropped # Sanity check if (asMissing) { .stop_if_not(nbrOfSegments(res, splitters=TRUE) == nbrOfSegments(this, splitters=TRUE)) } else { .stop_if_not(nbrOfSegments(res, splitters=TRUE) + length(regions) == nbrOfSegments(this, splitters=TRUE)) } verbose && exit(verbose) res }, protected=TRUE) setMethodS3("dropRegion", "AbstractCBS", function(fit, region, ...) { # Argument 'region': region <- Arguments$getIndex(region) dropRegions(fit, regions=region, ...) }, protected=TRUE) setMethodS3("shiftTCN", "AbstractCBS", abstract=TRUE, protected=TRUE) PSCBS/R/PairedPSCBS.callCopyNeutral.R0000644000176200001440000004251214564051545016564 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod callCopyNeutral # @aliasmethod callNTCN # # @title "Calls segments that have a neutral total copy number" # # \description{ # @get "title" (NTCN), # i.e. that have a TCN that corresponds to the ploidy of the genome. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # call to use.} # \item{...}{Additional arguments passed to the caller.} # \item{minSize}{An optional @integer specifying the minimum number # of data points in order to call a segments. If fewer data points, # then the call is set to @NA regardless.} # \item{force}{If @FALSE, and copy-neutral calls already exits, # then nothing is done, otherwise the calls are done.} # } # # \value{ # Returns a @see "PairedPSCBS" object with copy-neutral calls. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "callCopyNeutralByTCNofAB". # } # #*/########################################################################### setMethodS3("callCopyNeutral", "PairedPSCBS", function(fit, flavor=c("TCN|AB"), ..., minSize=1, force=FALSE) { # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'minSize': minSize <- Arguments$getDouble(minSize, range=c(1,Inf)) # Already done? segs <- as.data.frame(fit) calls <- segs$ntcnCall if (!force && !is.null(calls)) { return(invisible(fit)) } if (flavor == "TCN|AB") { fit <- callCopyNeutralByTCNofAB(fit, ..., force=force) } else { stop("Cannot call copy-neutral states. Unsupported flavor: ", flavor) } # Don't call segments with too few data points? if (minSize > 1) { segs <- as.data.frame(fit) ns <- segs$dhNbrOfLoci calls <- segs$ntcnCall calls[ns < minSize] <- NA segs$ntcnCall <- calls fit$output <- segs # Not needed anymore segs <- calls <- NULL } return(invisible(fit)) }) setMethodS3("callNTCN", "PairedPSCBS", function(...) { callCopyNeutral(...) }) setMethodS3("calcStatsForCopyNeutralABs", "PairedPSCBS", function(fit, ..., force=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'force': force <- Arguments$getLogical(force) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "calcStatsForCopyNeutralABs") segsNTCN <- fit$params$copyNeutralStats if (!force && !is.null(segsNTCN)) { verbose && exit(verbose) return(fit) } verbose && enter(verbose, "Identifying copy neutral AB segments") # Getting AB calls segs <- getSegments(fit, splitters=TRUE) isAB <- segs$abCall if (is.null(isAB)) { stop("Cannot call copy-neutral states, because allelic-balance calls have not been made yet.") } nABs <- sum(isAB, na.rm=TRUE) verbose && cat(verbose, "Number of AB segments: ", nABs) if (nABs == 0L) { stop("Cannot call copy-neutral states, because none of the segments are in allelic balance.") } C <- segs[,"tcnMean", drop=TRUE] isAB <- segs[,"abCall", drop=TRUE] n <- segs[,"tcnNbrOfSNPs", drop=TRUE] # "tcnNbrOfLoci"? /HB 2010-09-09 # Give more weight to longer regions weights <- n # Identify copy neutral AB segments isNeutralAB <- findNeutralCopyNumberState(C=C, isAI=!isAB, weights=weights, ..., flavor="maxPeak", verbose=verbose) nAB <- sum(isNeutralAB, na.rm=TRUE) verbose && cat(verbose, "Number of copy-neutral AB segments: ", nAB) if (nAB == 0L) { stop("Cannot call copy-neutral states, because none of the segments in allelic-balance are copy neutral.") } verbose && enter(verbose, "Extracting all copy neutral AB segments across all chromosomes into one big segment") # (a) Extract those fitNTCN <- extractSegments(fit, isNeutralAB) verbose && print(verbose, fitNTCN) verbose && exit(verbose) # (b) Turn into a single-chromosome data set fitNTCN <- extractSegments(fitNTCN, !isSegmentSplitter(fitNTCN)) isSplitter <- is.na(fitNTCN$output$chromosome) fitNTCN$data$chromosome <- 0L fitNTCN$output$chromosome <- 0L fitNTCN$output$chromosome[isSplitter] <- NA # (c) Turn into one big segment by dropping all change points ## nCPs <- nbrOfChangePoints(fitNTCN, ignoreGaps=TRUE) nCPs <- nbrOfSegments(fitNTCN, splitters=TRUE) - 1L if (nCPs >= 1L) { verbose && enter(verbose, "Dropping all change points") fitNTCN <- dropChangePoints(fitNTCN, idxs=nCPs:1, ignoreGaps=TRUE, update=TRUE, verbose=less(verbose, 5)) verbose && exit(verbose) } # Sanity check .stop_if_not(nbrOfSegments(fitNTCN) == 1L) verbose && exit(verbose) verbose && enter(verbose, "Bootstrap the identified copy-neutral states") fitNTCN <- bootstrapTCNandDHByRegion(fitNTCN, what="segment", force=TRUE, ..., verbose=less(verbose, 50)) segsNTCN <- getSegments(fitNTCN, simplified=FALSE) names <- colnames(segsNTCN) excl <- grep("(^chromosome|Id|Start|End|Call)$", names) segsNTCN <- segsNTCN[,-excl,drop=FALSE] # Sanity check .stop_if_not(ncol(segsNTCN) > 0L) verbose && exit(verbose) verbose && print(verbose, segsNTCN) verbose && exit(verbose) fit$params$copyNeutralStats <- segsNTCN invisible(fit) }, protected=TRUE) # calcStatsForCopyNeutralABs() ###########################################################################/** # @RdocMethod estimateDeltaCN # @alias estimateDeltaCN # @alias estimateDeltaCN.CBS # # @title "Estimates the length of one total copy-number (TCN) unit" # # \description{ # @get "title" # } # # @synopsis # # \arguments{ # \item{scale}{A @numeric scale factor in (0,Inf) used for rescaling # (multiplying) the final estimate with.} # \item{flavor}{Specifies which type of estimator should be used.} # \item{kappa}{Estimate of background signal (used by the \code{"1-kappa"} method).} # \item{adjust, quantile}{Tuning parameters (used by the \code{"delta(mode)"} method).} # \item{...}{Not used.} # } # # \value{ # Returns a positive scalar @numeric. # } # # \details{ # For parent-specific copy-number (PSCN) data, the TCN unit length is # estimated as \eqn{(1-kappa)/2}, where \eqn{kappa} is estimated from # data (by @see "PSCBS::estimateKappa"). # # For total copy-number (TCN) data (only), # } # # @author "HB" # # \seealso{ # @seeclass # } # # @keyword internal #*/########################################################################### setMethodS3("estimateDeltaCN", "PairedPSCBS", function(fit, scale=1, flavor=c("1-kappa", "delta(mode)"), kappa=estimateKappa(fit), adjust=0.2, quantile=0.95, ...) { # Argument 'scale': disallow <- c("NA", "NaN", "Inf") scale <- Arguments$getDouble(scale, range=c(0,Inf), disallow=disallow) # Argument 'flavor': flavor <- match.arg(flavor) if (flavor == "1-kappa") { # Argument 'kappa': disallow <- c("NA", "NaN", "Inf") kappa <- Arguments$getDouble(kappa, range=c(0,1), disallow=disallow) # Half a TCN unit length delta <- (1-kappa)/2 } else if (flavor == "delta(mode)") { # To please R CMD check rohCall <- abCall <- type <- NULL rm(list=c("rohCall", "abCall", "type")) segs <- getSegments(fit) segs <- subset(segs, !rohCall) segs <- subset(segs, !abCall) sigmas <- list() for (name in c("c1", "c2", "tcn")) { # FIXME/AD HOC: Here we assume certain fields fields <- sprintf("%s_%s%%", name, c(5,95)) if (all(is.element(fields, names(segs)))) { sigma <- segs[,fields[2]] - segs[,fields[1]] } else { if (name == "tcn") { n <- segs[,"tcnNbrOfLoci"] } else { n <- segs[,"dhNbrOfLoci"] n <- segs[,"tcnNbrOfLoci"] } n <- segs[,"tcnEnd"] - segs[,"tcnStart"] sigma <- 1/sqrt(n) } sigmas[[name]] <- sigma } segs <- segs[,c("c1Mean", "c2Mean", "tcnMean")] x <- unlist(segs, use.names=FALSE) w <- 1/unlist(sigmas, use.names=FALSE) keep <- is.finite(x) & is.finite(w) x <- x[keep]; w <- w[keep] w <- w / sum(w) d <- density(x, weights=w, adjust=adjust) ## plotDensity(d) tolMax <- max(d$y, na.rm=TRUE) tols <- seq(from=tolMax, to=0, length.out=100) stats <- data.frame(tolerance=tols, delta=NA_real_, count=NA_integer_) for (kk in seq_along(tols)) { tol <- tols[kk] px <- subset(findPeaksAndValleys(d, tol=tol), type == "peak")$x nx <- length(px) dx <- mean(diff(px)) stats[kk,"delta"] <- dx stats[kk,"count"] <- nx } stats <- subset(stats, is.finite(delta)) ## print(stats) delta <- median(stats[,"delta"]) } # Rescale delta <- scale * delta delta }, protected=TRUE) # estimateDeltaCN() ###########################################################################/** # @set class=PairedPSCBS # @RdocMethod callCopyNeutralByTCNofAB # # @title "Calls regions that are copy neutral" # # \description{ # @get "title" from the total copy numbers (TCNs) of segments # in allelic balance (AB). # } # # @synopsis # # \arguments{ # \item{fit}{A PairedPSCBS fit object as returned by # @see "PSCBS::segmentByPairedPSCBS".} # \item{delta}{A non-negative @double specifying the width of the # "acceptance" region. # Defaults to half of the distance between two integer TCN states, # i.e. 1/2. This argument should be shrunken as a function of # the amount of the normal contamination and other background signals.} # \item{alpha}{A @double in [0,0.5] specifying the significance level # of the confidence intervals used.} # \item{...}{Additional arguments passed to # @seemethod "calcStatsForCopyNeutralABs".} # \item{force}{If @TRUE, an already called object is skipped, otherwise not.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a @see "PairedPSCBS" fit object where a column # with the copy-neutral call. # } # # \details{ # ... # } # # %% examples "../incl/callCopyNeutralByTCNofAB.PairedPSCBS.Rex" # # @author "HB" # # @keyword internal #*/########################################################################### setMethodS3("callCopyNeutralByTCNofAB", "PairedPSCBS", function(fit, delta=estimateDeltaCN(fit), alpha=0.05, ..., force=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'delta': disallow <- c("NA", "NaN", "Inf") delta <- Arguments$getDouble(delta, range=c(0,Inf), disallow=disallow) # Argument 'alpha': disallow <- c("NA", "NaN", "Inf") alpha <- Arguments$getDouble(alpha, range=c(0,0.5), disallow=disallow) # Argument 'force': force <- Arguments$getLogical(force) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "callCopyNeutralByTCNofAB") verbose && cat(verbose, "Alpha: ", alpha) verbose && cat(verbose, "Delta CN: ", delta) segs <- getSegments(fit, splitters=TRUE, simplify=FALSE) # Nothing to do? if (!force && !is.null(segs$ntcnCall)) { # Copy neutral segments are already called verbose && cat(verbose, "Already called. Skipping.") verbose && exit(verbose) return(fit) } verbose && enter(verbose, "Calling copy-neutral segments") verbose && enter(verbose, "Retrieve TCN confidence intervals for all segments") # Calculate TCN bootstrap estimates, if missing probs <- c(alpha/2, 1-alpha/2) verbose && printf(verbose, "Interval: [%g,%g]\n", probs[1], probs[2]) keys <- sprintf("tcn_%g%%", 100*c(probs[1], probs[2])) missing <- keys[!is.element(keys, colnames(segs))] if (length(missing) > 0) { fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) segs <- getSegments(fit, splitters=TRUE, simplify=FALSE) # Assert that they exists missing <- keys[!is.element(keys, colnames(segs))] if (length(missing) > 0) { stop("INTERNAL ERROR: No such statistics: ", hpaste(missing)) } } verbose && exit(verbose) verbose && enter(verbose, "Estimating TCN confidence interval of copy-neutral AB segments") fit <- calcStatsForCopyNeutralABs(fit, ..., verbose=less(verbose, 5)) stats <- fit$params$copyNeutralStats verbose && cat(verbose, "Bootstrap statistics for copy-neutral AB segments:") verbose && print(verbose, stats) # Extract TCN stats cols <- grep("^(tcn_|tcnMean)", colnames(stats)) tcnStats <- stats[,cols,drop=FALSE] tcnStats <- unlist(tcnStats, use.names=TRUE) verbose && print(verbose, "TCN statistics:") verbose && print(verbose, tcnStats) # Assert confidence interval of interest missing <- keys[!is.element(keys, names(tcnStats))] if (length(missing) > 0) { stop("INTERNAL ERROR: No such statistics: ", hpaste(missing)) } mean <- tcnStats["tcnMean"] ci <- tcnStats[keys] verbose && printf(verbose, "%g%%-confidence interval of TCN mean for the copy-neutral state: [%g,%g] (mean=%g)\n", 100*(1-alpha), ci[1], ci[2], mean) verbose && exit(verbose) verbose && enter(verbose, "Identify all copy-neutral segments") verbose && printf(verbose, "DeltaCN: +/-%g\n", delta) range <- ci + delta*c(-1,+1) verbose && printf(verbose, "Call (\"acceptance\") region: [%g,%g]\n", range[1], range[2]) # Get TCN confidence intervals for all segments ci <- segs[,keys] ci <- as.matrix(ci) ## WAS: If a confidence interval is completely within the ## calling region, call it ## isNTCN <- (range[1] <= ci[,1] & ci[,2] <= range[2]) # If a segments confidence interval is completely outside the # copy-neutral region ("H_0"), that is, it is completely within # the rejection region ("H_1"), then the H_0 hypothesis that the # segment is copy-neutral in TCN is rejected. isLoss <- (ci[,2] < range[1]) # (a) completely below, or isGain <- (ci[,1] > range[2]) # (b) completely above. isNTCN <- (!isLoss & !isGain) # => completely inside => not rejected. nbrOfSegs <- nrow(segs) nbrOfABs <- sum(segs$abCall, na.rm=TRUE) nbrOfCNs <- sum(isNTCN, na.rm=TRUE) verbose && cat(verbose, "Total number of segments: ", nbrOfSegs) verbose && cat(verbose, "Number of segments called allelic balance: ", nbrOfABs) verbose && cat(verbose, "Number of segments called copy neutral: ", nbrOfCNs) nbrOfCNABs <- sum(isNTCN & segs$abCall, na.rm=TRUE) verbose && cat(verbose, "Number of AB segments called copy neutral: ", nbrOfCNABs) nbrOfCNNonABs <- sum(isNTCN & !segs$abCall, na.rm=TRUE) verbose && cat(verbose, "Number of non-AB segments called copy neutral: ", nbrOfCNNonABs) verbose && exit(verbose) # Sanity check # # All previously called AB regions should remain called here as well # .stop_if_not(all(isNTCN[isNeutralAB], na.rm=TRUE)) segs$ntcnCall <- isNTCN params <- fit$params params$deltaCN <- delta params$ntcnRange <- range fitC <- fit fitC$output <- segs fitC$params <- params verbose && exit(verbose) fitC }, protected=TRUE) # callCopyNeutralByTCNofAB() ############################################################################## # HISTORY # 2013-10-21 [HB] # o ROBUSTNESS: Now calcStatsForCopyNeutralABs() only bootstraps the # segments of the subsetted copy-neutral segments. # 2013-04-17 [HB] # o BUG FIX: Internal calcStatsForCopyNeutralABs() would give an error # if there was exactly two AH segments. # 2013-03-19 [HB] # o CALLING: Defined a formal hypthesis test for how segments are called # copy-neutral in TCN (NTCN), with the null hypothesis being that a # segment is NTCN. In order for a segment to not be NTCN, its confidence # interval has to be completely outside the null region. This changed # how callCopyNeutralByTCNofAB() for PairedPSCBS calls segments; it is # now a bit more conservative in rejecting NTCN. # o ROBUSTNESS: Now calcStatsForCopyNeutralABs() for PairedPSCBS does # a better job in identifying the TCN mode of the AB segments. # o Now callCopyNeutralByTCNofAB() records parameters 'deltaCN' and # 'ntcnRange'. # 2012-09-21 [HB] # o BUG FIX: Recent updates in how nbrOfChangePoints() is calculated, # caused callGNL() to throw an exception. Added argument 'ignoreGaps' # to nbrOfChangePoints(). # 2012-07-02 [HB] # o Renamed callTCNN() to callNTCN(). # 2012-06-24 [HB] # o Renamed callCN() to callTCNN() in order not to confuse it with # copy numbers in general. # 2012-06-03 [HB] # o Added estimateDeltaCN() for PairedPSCBS, which is calculated as a # function of the amount of normal contamination as currently estimated # by estimateKappa(). # o Now callCopyNeutralByTCNofAB() runs bootstrapping if quantiles are # missing. # 2012-02-25 [HB] # o Added internal calcStatsForCopyNeutralABs() for PairedPSCBS. # 2012-02-24 [HB] # o Now callCopyNeutralByTCNofAB() calls all segements, not just those in AB. # o Now the copy-neutral calls are named 'cnCall' (not 'neutralCall'). # o Added callCN()/callCopyNeutral(). # o Added callCopyNeutralByTCNofAB() for PairedPSCBS. The method was # adopted from callCopyNeutralRegions() in aroma.cn, whose history has # been incorporated below. # o Created. # 2010-09-15* [HB] # o Added Rdocs for callCopyNeutralRegions(). # 2010-09-09* [HB] # o Added callCopyNeutralRegions() for PairedPSCBS. ############################################################################## PSCBS/R/PairedPSCBS.callAB.R0000644000176200001440000002246614564051545014607 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod callAB # @aliasmethod callAllelicBalance # # @title "Calls segments that are in allelic balance" # # \description{ # @get "title", i.e. that have equal minor and major copy numbers. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # call to use.} # \item{...}{Additional arguments passed to the caller.} # \item{minSize}{An optional @integer specifying the minimum number # of data points in order to call a segments. If fewer data points, # then the call is set to @NA regardless.} # \item{xorCalls}{If @TRUE, a region already called LOH, will # for consistency never be called AB, resulting in either an AB # call set to @FALSE or @NA (as explained below).} # \item{force}{If @FALSE, and allelic-balance calls already exits, # then nothing is done, otherwise the calls are done.} # } # # \value{ # Returns a @see "PairedPSCBS" object with allelic-balance calls. # } # # \section{AB and LOH consistency}{ # Biologically, a segment can not be both in allelic balance (AB) and # in loss-of-heterozygosity (LOH) at the same time. # To avoid reporting such inconsistencies, the LOH caller will, # if argument \code{xorCalls=TRUE}, never report a segment to be in # LOH if it is already called to be in AB. # However, regardless of of the AB call, a segment is still always # tested for LOH, to check weather the LOH caller is consistent with the # AB caller or not. Thus, in order to distinguish the case where # the AB caller and LOH caller agree from when they disagree, # we report either (AB,LOH)=(TRUE,FALSE) or (TRUE,NA). The former is # reported when they are consistent, and the latter when they are not, # or when the AB caller could not call it. # } # # @author "HB" # # \seealso{ # Internally, one of the following methods are used: # @seemethod "callAllelicBalanceByDH". # } # #*/########################################################################### setMethodS3("callAB", "PairedPSCBS", function(fit, flavor=c("DeltaAB*"), ..., minSize=1, xorCalls=TRUE, force=FALSE) { # Argument 'flavor': flavor <- match.arg(flavor) # Argument 'minSize': minSize <- Arguments$getDouble(minSize, range=c(1,Inf)) # Argument 'xorCalls': xorCalls <- Arguments$getLogical(xorCalls) # Already done? segs <- as.data.frame(fit) calls <- segs$abCall if (!force && !is.null(calls)) { return(invisible(fit)) } if (flavor == "DeltaAB*") { fit <- callAllelicBalanceByDH(fit, ...) } else { stop("Cannot call allelic balance. Unsupported flavor: ", flavor) } # Don't call segments with too few data points? if (minSize > 1) { segs <- as.data.frame(fit) ns <- segs$dhNbrOfLoci calls <- segs$abCall calls[ns < minSize] <- NA segs$abCall <- calls fit$output <- segs # Not needed anymore segs <- calls <- NULL } # Don't call a segment AB if it already called LOH? if (xorCalls) { segs <- as.data.frame(fit) if (is.element("lohCall", names(segs))) { calls <- segs$abCall otherCalls <- segs$lohCall # If called (TRUE) and already called (TRUE) # by the other caller, call it as NA. calls[calls & otherCalls] <- NA segs$abCall <- calls fit$output <- segs } } return(invisible(fit)) }) setMethodS3("callAllelicBalance", "default", function(...) { callAB(...) }) ###########################################################################/** # @set class=PairedPSCBS # @RdocMethod callAllelicBalanceByDH # # @title "Calls segments that are in allelic balance" # # \description{ # @get "title" by thresholding on DH using a predetermined threshold. # The variability of the DH mean levels is taken into account via a # bootstrap estimator. # } # # @synopsis # # \arguments{ # \item{flavor}{A @character string specifying which type of # call to use.} # \item{delta}{(Tuning parameter) A non-negative @numeric threshold.} # \item{alpha}{A @numeric in [0,1] specifying the upper and lower # quantiles calculated by the bootstrap estimator.} # \item{...}{Additional arguments passed to the bootstrap estimator # @seemethod "bootstrapTCNandDHByRegion".} # } # # \value{ # Returns a @see "PairedPSCBS" object with allelic-balance calls. # } # # @author "HB" # # \section{Algorithm}{ # \itemize{ # \item Foo # \item Bar # } # } # # \seealso{ # Instead of calling this method explicitly, it is recommended # to use the @seemethod "callAllelicBalance" method. # } # # @keyword internal #*/########################################################################### setMethodS3("callAllelicBalanceByDH", "PairedPSCBS", function(fit, delta=estimateDeltaAB(fit, flavor="qq(DH)"), alpha=0.05, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'delta': delta <- Arguments$getDouble(delta, range=c(0,Inf)) # Argument 'alpha': alpha <- Arguments$getDouble(alpha, range=c(0,1)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling segments of allelic balance from one-sided DH bootstrap confidence intervals") verbose && cat(verbose, "delta (offset adjusting for bias in DH): ", delta) verbose && cat(verbose, "alpha (CI quantile; significance level): ", alpha) # Calculate DH confidence intervals, if not already done probs <- c(alpha, 1-alpha) fit <- bootstrapTCNandDHByRegion(fit, probs=probs, ..., verbose=less(verbose, 50)) segs <- as.data.frame(fit) # Extract confidence interval alphaTag <- sprintf("%g%%", 100*alpha) column <- sprintf("dh_%s", alphaTag) # Sanity checks .stop_if_not(is.element(column, colnames(segs))) # One-sided test verbose && enter(verbose, "Calling segments") value <- segs[,column, drop=TRUE] call <- (value < delta) nbrOfCalls <- sum(call, na.rm=TRUE) verbose && printf(verbose, "Number of segments called allelic balance (AB): %d (%.2f%%) of %d\n", nbrOfCalls, 100*nbrOfCalls/nrow(segs), nrow(segs)) verbose && exit(verbose) segs$abCall <- call fit$output <- segs # Append 'delta' and 'alpha' to parameters params <- fit$params params$deltaAB <- delta params$alphaAB <- alpha fit$params <- params verbose && exit(verbose) fit }, protected=TRUE) # callAllelicBalanceByDH() ############################################################################## # HISTORY # 2012-01-15 # o DOCUMENTATION: Added details to the help of callLOH() and callAB() on # the difference between (AB,LOH)=(TRUE,FALSE) and (AB,LOH)=(TRUE,NA). # 2011-07-07 # o BUG FIX: Consecutive calls to callAB(..., force=TRUE) would append # additional 'abCall' columns to the segmentation table instead of # replacing existing calls. # 2011-06-14 # o Updated code to recognize new column names. # 2011-05-29 # o Renamed all arguments, variables, function named 'tau' to 'delta'. # 2011-04-14 # o BUG FIX: Argument 'minSize' of callAB() and callLOH() had no effect. # 2011-04-12 # o Added argument 'minSize' to callAB() for PairedPSCBS. # o Added argument 'xorCalls' to callAB() for PairedPSCBS. # 2011-04-10 # o callAllelicBalance() calls callAB(). # 2011-04-09 # o Now callAllelicBalance(..., force=FALSE) skips the caller if allelic- # balance calls already exist. # 2011-04-08 # o Added Rdoc for callAllelicBalance() and callAllelicBalanceByDH(). # o Extracted from PairedPSCBS.CALL.R. # 2011-02-03 # o Updated default for 'tauAB' of callABandHighAI() and callABandLowC1() # to be estimated from data using estimateTauAB(). # 2010-12-07 # o Added callLowC1ByC1() and callABandLowC1(). # 2010-11-27 # o Corrected verbose output to call results. # 2010-11-26 [HB] # o Now all call functions estimate symmetric bootstrap quantiles for # convenince of plotting confidence intervals. # o BUG FIX: callABandHighAI() for PairedPSCBS used the old DH-only # bootstrap method. # o BUG FIX: The call functions, for instance callABandHighAI(), would throw # 'Error in quantile.default(x, probs = alpha) : missing values and NaN's # not allowed if 'na.rm' is FALSE' unless bootstrapTCNandDHByRegion() was # run before. # 2010-11-22 [HB] # o Added more verbose output to callABandHighAI(). # o Updated callAllelicBalanceByDH() and callExtremeAllelicImbalanceByDH() # to utilize bootstrapTCNandDHByRegion(). # 2010-10-25 [HB] # o Relaced argument 'ciRange' with 'alpha' for callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH(). # o Renamed callAllelicBalance() to callAllelicBalanceByDH() and # callExtremeAllelicImbalanceByDH() to callExtremeAllelicImbalance(). # o Added arguments 'alphaAB' and 'alphaHighAI' to callABandHighAI(). # o Added sanity checks to the call methods. # o Now arguments '...' to callABandHighAI() are passed down. # o Now also arguments '...' to callAllelicBalance() and # callExtremeAllelicImbalance() are passed to bootstrapDHByRegion(). # o Added argument 'ciRange' to callAllelicBalance() and # callExtremeAllelicImbalance(). # 2010-09-16 [HB] # o Added callABandHighAI(). # o Added callAllelicBalance() and callExtremeAllelicImbalance(). # o Created. ############################################################################## PSCBS/R/testROH.R0000644000176200001440000001251114564051545013011 0ustar liggesusers###########################################################################/** # @set "class=numeric" # @RdocMethod testROH # # @title "Tests if a segment is in Run-of-Homozygosity (ROH)" # # \description{ # @get "title". # } # # @synopsis # # \arguments{ # \item{muN}{An @numeric @vector of J genotype calls in # \{0,1/2,1\} for AA, AB, and BB, respectively, # and @NA for non-polymorphic loci.} # \item{csN}{(optional) A @numeric @vector of J genotype confidence scores. # If @NULL, ad hoc scores calculated from \code{betaN} are used.} # \item{betaN}{(optional) A @numeric @vector of J matched normal BAFs # in [0,1] (due to noise, values may be slightly outside as well) # or @NA for non-polymorphic loci.} # \item{minNbrOfSnps}{Minimum number of SNPs required to test segment. # If not tested, @NA is returned.} # \item{delta}{A @double scalar specifying the maximum (weighted) # proportion of heterozygous SNPs allowed in an ROH region.} # \item{...}{Not used.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a @logical. # } # # @author "PN, HB" # # @keyword internal #*/########################################################################### setMethodS3("testROH", "numeric", function(muN, csN=NULL, betaN=NULL, minNbrOfSnps=1, delta=1/12, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'muN': muN <- Arguments$getDoubles(muN, range=c(0,1)) nbrOfSnps <- length(muN) length2 <- rep(nbrOfSnps, times=2) # Argument 'csN' & 'betaN': if (!is.null(csN)) { csN <- Arguments$getDoubles(csN, range=c(0,1), length=length2) } else { if (!is.null(betaN)) { betaN <- Arguments$getDoubles(betaN, length=length2) } } # Argument 'minNbrOfSnps': minNbrOfSnps <- Arguments$getInteger(minNbrOfSnps, range=c(1,Inf)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Testing for ROH") # Default ROH call call <- NA verbose && cat(verbose, "Number of SNPs: ", nbrOfSnps) # Nothing todo? if (nbrOfSnps < minNbrOfSnps) { verbose && exit(verbose) return(call) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calculate genotype confidence scores (from betaN)? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.null(csN)) { if (!is.null(betaN)) { verbose && enter(verbose, "Calculating confidence scores") # Assuming naive genotyping a'la aroma.light::callNaiveGenotypes() # was used to call genotypes 'muN' from 'betaN'. # AD HOC: We also have to assume that the thresholds were 1/3 and 2/3. a <- 1/3 # was fit$x[1] b <- 2/3 # was fit$x[2] # AD HOC: We have to make some assumption about which SNPs are diploid. # Assume all for now isDiploid <- rep(TRUE, times=nbrOfSnps) # KNOWN ISSUE: Scores for homozygotes are in [0,1/3], whereas # heterzygotes are in [0,1/6]. /PN 2011-11-11 csN[isDiploid] <- rowMins(abs(cbind(betaN[isDiploid]-a, betaN[isDiploid]-b)), useNames=FALSE) verbose && exit(verbose) } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call ROH # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify heterozygous SNPs isHet <- (muN == 1/2) verbose && print(verbose, summary(isHet)) # With or without genotype confidence scores? if (!is.null(csN)) { # 0-1 weights (just to make sure) # Weights summing to one w <- csN / sum(csN, na.rm=TRUE) wnHets <- sum(isHet*w, na.rm=TRUE) wnSnps <- sum(w, na.rm=TRUE) # == 1 /HB # Sanity check .stop_if_not(isZero(wnSnps - 1.0, eps=sqrt(.Machine$double.eps))) } else { wnHets <- sum(isHet, na.rm=TRUE) wnSnps <- 1 } propHets <- wnHets/wnSnps verbose && print(verbose, propHets) call <- (propHets < delta) verbose && print(verbose, call) # Record parameter settings attr(call, "minNbrOfSnps") <- minNbrOfSnps attr(call, "delta") <- delta verbose && exit(verbose) call }) # testROH() ############################################################################## # HISTORY # 2014-03-30 [HB] # o GENERALIZATION: Now testROH() default to equal confidence scores # whenever neither 'csN' not 'betaN' is given. This means that # callROH() can also be done if only 'muN' was provided. # o Updated the ordering and the defaults of testROH() arguments to make # it clear that 'betaN' is optional and only used if 'csN' is not given. # 2013-03-08 [HB] # o Added Rdoc help. # 2012-05-30 [HB] # o Now testROH() return parameter settings as attributes. # 2011-11-21 [HB] # o BUG FIX: The internal sanity check on weights was slightly too # conservative. # 2011-11-12 [HB] # o Renamed argument 'tauROH' to 'delta', cf. how we do for AB and LOH. # o Added argument 'minNbrOfSnps' to testROH(). # o Added verbose output. # 2011-11-12 [PN] # o Implemented a naive caller based on the weighted proportion of hets # in the segment. # 2011-11-04 [HB] # o Added skeleton for testROH(). # o Created. ############################################################################## PSCBS/R/PairedPSCBS.PLOT2.R0000644000176200001440000002537314564051545014331 0ustar liggesuserssetMethodS3("plotTracks2", "PairedPSCBS", function(x, panels=NULL, calls=".*", pch=".", col=NULL, cex=1, lwd=2, changepoints=FALSE, grid=FALSE, quantiles=c(0.05,0.95), xlim=NULL, Clim=c(0,3*ploidy(x)), Blim=c(0,1), xScale=1e-6, ..., add=FALSE, subplots=!add && (length(panels) > 1), verbose=FALSE) { # To please R CMD check fit <- x # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': if (nbrOfChromosomes(fit) > 1) { stop("Multiple chromosomes detected. Not yet implemented.") } # Argument 'panels': panels <- unique(panels) panelsOrg <- panels panels <- gsub("[-*]", "", panelsOrg) knownPanels <- c("tcn", "tcn,c1,c2", "tcn,c1", "tcn,c2", "c1,c2", "c1", "c2", "dh", "betaN", "betaT", "betaTN") panels <- match.arg(panels, choices=knownPanels, several.ok=TRUE) panels <- panelsOrg # Argument 'calls': if (!is.null(calls)) { calls <- sapply(calls, FUN=Arguments$getRegularExpression) } # Argument 'changepoints': changepoints <- Arguments$getLogical(changepoints) # Argument 'grid': grid <- Arguments$getLogical(grid) # Argument 'xlim': if (!is.null(xlim)) { xlim <- Arguments$getNumerics(xlim, length=c(2,2)) } # Argument 'xScale': xScale <- Arguments$getNumeric(xScale, range=c(0,Inf)) # Argument 'add': add <- Arguments$getLogical(add) # Argument 'Clim': if (!add) { Clim <- Arguments$getNumerics(Clim, length=c(2L,2L), disallow=c("Inf", "NA", "NaN")) } # Argument 'subplots': subplots <- Arguments$getLogical(subplots) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Plotting PSCN panels") # Extract the input data data <- getLocusData(fit) if (is.null(data)) { stop("Cannot plot segmentation results. No input data available.") } chromosomes <- getChromosomes(fit) chromosome <- chromosomes[1] x <- data$x CT <- data$CT rho <- data$rho betaT <- data$betaT betaN <- data$betaN betaTN <- data$betaTN muN <- data$muN rho <- data$rho hasDH <- !is.null(rho) if (hasDH) { isHet <- !is.na(rho) isSnp <- isHet } else { isSnp <- (!is.na(betaTN) & !is.na(muN)) isHet <- isSnp & (muN == 1/2) } nbrOfLoci <- length(x) # BACKWARD COMPATIBILITY: # If 'rho' is not available, recalculate it from tumor BAFs. # NOTE: This should throw an error in the future. /HB 2013-10-25 if (!hasDH) { rho <- rep(NA_real_, times=nbrOfLoci) rho[isHet] <- 2*abs(betaTN[isHet]-1/2) warning(sprintf("Locus-level DH signals ('rho') were not available in the %s object and therefore recalculated from the TumorBoost-normalized tumor BAFs ('betaTN').", class(fit)[1L])) } # Extract the segmentation segs <- as.data.frame(fit) # Identify available calls if (!is.null(calls)) { verbose && enter(verbose, "Identifying calls") pattern <- "Call$" callColumns <- grep(pattern, colnames(segs), value=TRUE) if (length(callColumns) > 0) { keep <- sapply(calls, FUN=function(pattern) { (regexpr(pattern, callColumns) != -1) }) if (is.matrix(keep)) { keep <- rowAnys(keep, useNames=FALSE) } callColumns <- callColumns[keep] callLabels <- gsub(pattern, "", callColumns) callLabels <- toupper(callLabels) } verbose && cat(verbose, "Call columns:") verbose && print(verbose, callColumns) verbose && exit(verbose) } else { callColumns <- NULL } if (chromosome != 0) { chrTag <- sprintf("Chr%02d", chromosome) } else { chrTag <- "" } if (xScale != 1) { x <- xScale * x if (is.null(xlim)) { xlim <- range(x, na.rm=TRUE) } else { xlim <- xScale * xlim } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Number of panels? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfPanels <- length(panels) if (subplots) { subplots(nbrOfPanels, ncol=1) par(mar=c(1,4,1,2)+1) } # Color loci by genotype if (hasDH) { colMu <- c("gray", "black")[!is.na(rho) + 1] } else { colMu <- c("gray", "black")[(muN == 1/2) + 1] } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each panel... # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - for (pp in seq_len(nbrOfPanels)) { panel <- panels[pp] verbose && enter(verbose, sprintf("Panel #%d ('%s') of %d", pp, panel, length(panels))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Setup empty plot # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!add) { verbose && enter(verbose, "Creating empty plot") tracks <- strsplit(panel, split=",", fixed=TRUE)[[1]] tracks <- gsub("[-*]", "", tracks) # Defaults ylim <- Clim ylab <- paste(toupper(tracks), collapse=", ") if (any(is.element(c("betaN", "betaT", "betaTN", "dh"), tracks))) { ylim <- Blim } verbose && cat(verbose, "ylim:") verbose && print(verbose, ylim) plot(NA, xlim=xlim, ylim=ylim, ylab=ylab) # Geometrical annotations stext(side=3, pos=1, chrTag) if (grid) { abline(h=seq(from=0, to=ylim[2], by=2), lty=3, col="gray") abline(h=0, lty=1, col="black") } verbose && exit(verbose) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Scatter tracks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - tracks <- strsplit(panel, split=",", fixed=TRUE)[[1]] keep <- grep("-", tracks, fixed=TRUE, invert=TRUE) tracks <- tracks[keep] verbose && cat(verbose, "Number tracks with scatter: ", length(tracks)) verbose && cat(verbose, "Tracks with scatter:") verbose && print(verbose, tracks) nbrOfTracks <- length(tracks) for (tt in seq_len(nbrOfTracks)) { track <- tracks[tt] verbose && enter(verbose, sprintf("Scatter track #%d ('%s') of %d", tt, track, nbrOfTracks)) track <- gsub("[-*]", "", track) # Defaults colT <- if (is.null(col)) "black" else col if (track == "tcn") { y <- CT } else if (track == "c1") { y <- 1/2*(1-rho)*CT } else if (track == "c2") { y <- 1/2*(1+rho)*CT } else if (track == "betaN") { y <- betaN colT <- if (is.null(col)) colMu else col ylab <- expression(BAF[N]) ylim <- Blim } else if (track == "betaT") { y <- betaT colT <- if (is.null(col)) colMu else col ylab <- expression(BAF[T]) ylim <- Blim } else if (track == "betaTN") { y <- betaTN colT <- if (is.null(col)) colMu else col ylab <- expression(BAF[T]^"*") ylim <- Blim } else if (track == "dh") { y <- rho colT <- if (is.null(col)) colMu[isHet] else col ylab <- "DH" ylim <- Blim } else { y <- NULL } # Nothing to do? if (!is.null(y)) { points(x, y, pch=pch, cex=cex, col=colT) } verbose && exit(verbose) } # for (tt ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segment tracks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - tracks <- strsplit(panel, split=",", fixed=TRUE)[[1]] keep <- grep("*", tracks, fixed=TRUE) tracks <- gsub("[-*]", "", tracks[keep]) # Keep only supported tracks tracksWithLevels <- c("tcn", "betaTN", "c1", "c2", "dh") .stop_if_not(all(is.element(tracks, tracksWithLevels))) tracks <- intersect(tracks, tracksWithLevels) verbose && cat(verbose, "Number tracks with levels: ", length(tracks)) verbose && cat(verbose, "Tracks with levels:") verbose && print(verbose, tracks) nbrOfTracks <- length(tracks) for (tt in seq_len(nbrOfTracks)) { track <- tracks[tt] verbose && enter(verbose, sprintf("Level track #%d ('%s') of %d", tt, track, nbrOfTracks)) if (track == "tcn") { colT <- "purple" } else if (track == "c1") { colT <- "blue" } else if (track == "c2") { colT <- "red" } else if (track == "betaTN") { colT <- "orange" } else if (track == "dh") { colT <- "orange" } else { colT <- if (is.null(col)) "black" else col } # Nothing to do? if (track != "betaTN") { drawConfidenceBands(fit, what=track, quantiles=quantiles, col=colT, xScale=xScale) } drawLevels(fit, what=track, col=colT, lwd=lwd, xScale=xScale) verbose && exit(verbose) } # for (tt ...) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Draw change points? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (changepoints) { segs <- as.data.frame(fit) xStarts <- segs[,"tcnStart"] xEnds <- segs[,"tcnEnd"] xs <- sort(unique(c(xStarts, xEnds))) abline(v=xScale*xs, lty=1, col="gray") } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # For each panel of tracks, annotate with calls? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (length(callColumns) > 0) { for (cc in seq_along(callColumns)) { callColumn <- callColumns[cc] callLabel <- callLabels[cc] verbose && enter(verbose, sprintf("Call #%d ('%s') of %d", cc, callLabel, length(callColumns))) verbose && cat(verbose, "Column: ", callColumn) segsT <- segs[,c("dhStart", "dhEnd", callColumn)] isCalled <- which(segsT[[callColumn]]) segsT <- segsT[isCalled,1:2,drop=FALSE] verbose && printf(verbose, "Number of segments called %s: %d\n", callLabel, nrow(segsT)) segsT <- xScale * segsT verbose && str(verbose, segsT) side <- 2*((cc+1) %% 2) + 1 # For each segment called... for (ss in seq_len(nrow(segsT))) { x0 <- segsT[ss,1,drop=TRUE] x1 <- segsT[ss,2,drop=TRUE] abline(v=c(x0,x1), lty=3, col="gray") xMid <- (x0+x1)/2 mtext(side=side, at=xMid, line=-1, cex=0.7, col="#666666", callLabel) } # for (ss in ...) verbose && exit(verbose) } # for (cc in ...) } # if (length(callColumns) > 0) verbose && exit(verbose) } # for (pp ...) verbose && exit(verbose) invisible() }, protected=TRUE) # plotTracks2() PSCBS/R/PairedPSCBS.callROH.R0000644000176200001440000001146114564051545014746 0ustar liggesusers##########################################################################/** # @set class=PairedPSCBS # @RdocMethod callROH # @alias callROH.NonPairedPSCBS # # @title "Calls segments that are in ROH" # # \description{ # @get "title", i.e. that have no (true) heterozygous genotypes. # Run of homozygosity (ROH) is a property of the normal (germline) sample. # } # # @synopsis # # \arguments{ # \item{...}{Additional arguments passed to @see "testROH".} # \item{updateMeans}{If @TRUE, DH and (C1,C2) mean levels are set # to @NA for segments called ROH, otherwise not.} # \item{force}{If @FALSE, and ROH calls already exits, # then nothing is done, otherwise the calls are done.} # \item{verbose}{See @see "R.utils::Verbose".} # } # # \value{ # Returns a @see "PairedPSCBS" object with ROH calls. # } # # @author "PN, HB" # # \seealso{ # Internally, @see "testROH" is used. # To call allelic balance (AB) see @seemethod "callAB". # To call loss of heterozygosity (LOH) see @seemethod "callLOH". # } #*/########################################################################### setMethodS3("callROH", "PairedPSCBS", function(fit, ..., updateMeans=TRUE, force=FALSE, verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling ROH") # Already done? segs <- getSegments(fit) calls <- segs$rohCall if (!force && !is.null(calls)) { return(invisible(fit)) } nbrOfSegments <- nrow(segs) calls <- rep(NA, times=nbrOfSegments) if (is.null(calls)) { segs <- cbind(segs, rohCall=calls) } delta <- NA_real_ # For each segment... for (ss in seq_len(nbrOfSegments)) { verbose && enter(verbose, sprintf("Segment #%d of %d", ss, nbrOfSegments)) fitT <- extractSegment(fit, ss) # Call only "non-splitter" segments if (nbrOfSegments(fitT) > 0L) { callSS <- callROHOneSegment(fitT, ..., verbose=less(verbose, 1)) calls[ss] <- callSS if (is.na(delta) && !is.na(callSS)) { delta <- attr(callSS, "delta") } } verbose && exit(verbose) } # for (ss ...) verbose && cat(verbose, "ROH calls:") verbose && str(verbose, calls) verbose && print(verbose, summary(calls)) segs$rohCall <- calls fit$output <- segs # Append parameters params <- fit$params params$deltaROH <- delta fit$params <- params # Set DH and (C1,C2) mean levels to NA? if (updateMeans) { fit <- updateMeans(fit, from="segments", adjustFor="roh", verbose=less(verbose, 20)) } verbose && exit(verbose) invisible(fit) }) # callROH() # This method calls ROH for a single-segment PairedPSCBS object setMethodS3("callROHOneSegment", "PairedPSCBS", function(fit, ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Calling ROH for a single segment") # Make sure that there is only a single segment in this object .stop_if_not(nbrOfSegments(fit, splitters=TRUE) == 1L) # Extract the locus-level data for the segment tested data <- getLocusData(fit) # Keep only SNPs: # SNPs are identifies as those loci that have non-missing # 'betaTN' & 'muN', cf. segmentByPairedPSCBS(). isSnp <- (!is.na(data$betaTN) & !is.na(data$muN)) nbrOfSnps <- sum(isSnp) verbose && cat(verbose, "Number of SNPs: ", nbrOfSnps) data <- data[isSnp,] # Extract that SNP signals used for calling ROH betaN <- data$betaN muN <- data$muN csN <- data$csN # Genotyping confidence scores, if available # Test for ROH fit <- testROH(muN=muN, csN=csN, betaN=betaN, ..., verbose=less(verbose, 10)) # Get the ROH call (TRUE, FALSE, or NA) call <- fit verbose && exit(verbose) call }, private=TRUE) ############################################################################## # HISTORY # 2014-03-29 [HB] # o BUG FIX: In rare cases, callROH() could throw "Error in if (is.na(delta)) # { : argument is of length zero". # 2012-05-30 [HB] # o Now callROH() records paramter 'deltaROH' in the results. # 2011-11-26 [HB] # o Added argument 'updateMeans=TRUE' to callROH() for PairedPSCBS. # 2011-11-12 [HB] # o BUG FIX: ROH calls should be stored in column 'rohCall' (not 'rohCalls'). # 2011-11-04 [HB] # o Added callROH() for PairedPSCBS. # o Created. ############################################################################## PSCBS/R/PairedPSCBS.BOOT.R0000644000176200001440000010723514564051545014232 0ustar liggesusers###########################################################################/** # @set class=PairedPSCBS # @RdocMethod bootstrapTCNandDHByRegion # # @title "Estimate confidence intervals of TCN and DH segment levels" # # \description{ # @get "title" using bootstrap. # } # # @synopsis # # \arguments{ # \item{B}{A positive @integer specifying the number of bootstrap samples.} # \item{boot}{Alternatively, to generating \code{B} bootstrap samples, # this specifies a pre-generated set of bootstrap samples as # returned by \code{bootstrapSegmentsAndChangepoints()}.} # \item{...}{Additional arguments passed to \code{bootstrapSegmentsAndChangepoints()}.} # \item{probs}{The default quantiles to be estimated.} # \item{statsFcn}{A (optional) @function that estimates confidence # intervals given locus-level data. # If @NULL, the @see "stats::quantile" function is used.} # \item{what}{A @character @vector specifying what to bootstrap.} # \item{force}{If @TRUE, already existing estimates are ignored, # otherwise not.} # \item{verbose}{See @see "R.utils::Verbose".} # \item{.debug}{(internal) If @TRUE, additional sanity checks are # performed internally.} # } # # \value{ # Returns a @see "PairedPSCBS" object. # } # # @author "HB" #*/########################################################################### setMethodS3("bootstrapTCNandDHByRegion", "PairedPSCBS", function(fit, B=1000L, boot=NULL, ..., probs=c(0.025, 0.050, 0.95, 0.975), statsFcn=NULL, what=c("segment", "changepoint"), force=FALSE, verbose=FALSE, .debug=FALSE) { # Settings for sanity checks tol <- getOption("PSCBS/sanityChecks/tolerance", 0.0005) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Local functions # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - summarizeSamples <- function(X, statsFcn, stats=NULL, what=c("segment", "changepoint"), ..., verbose=FALSE) { # Argument 'X': .stop_if_not(is.array(X)) dim <- dim(X) .stop_if_not(length(dim) == 3L) # Argument 'statsFcn': .stop_if_not(is.function(statsFcn)) statsT <- statsFcn(1) .stop_if_not(!is.null(names(statsT))) nbrOfStats <- length(statsT) statsNames <- names(statsT) statsT <- NULL # Not needed anymore # Argument 'stats': if (!is.null(stats)) { .stop_if_not(is.data.frame(stats)) } # Argument 'what': what <- match.arg(what) whatC <- capitalize(what) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } dimnames <- dimnames(X) fields <- dimnames[[3L]] verbose && enter(verbose, sprintf("Summarizing bootstrapped %s (%s) data", what, paste(sQuote(fields), collapse=", "))) # Allocate JxQxF matrix S dim[2L] <- nbrOfStats dimnames[[2L]] <- statsNames S <- array(NA_real_, dim=dim, dimnames=dimnames) verbose && str(verbose, S) for (kk in seq_along(fields)) { field <- fields[kk] verbose && enter(verbose, sprintf("Field #%d ('%s') of %d", kk, field, length(fields))) Xkk <- X[,,kk,drop=FALSE] # An JxB matrix dim(Xkk) <- dim(Xkk)[-3L] # Sanity check .stop_if_not(is.matrix(Xkk)) .stop_if_not(nrow(Xkk) == dim(X)[1L]) .stop_if_not(ncol(Xkk) == B) for (jj in seq_len(dim(X)[1L])) { verbose && enter(verbose, sprintf("%s #%d of %d", whatC, jj, dim(X)[1L])) Xkkjj <- Xkk[jj,,drop=TRUE] # A vector of length B S[jj,,kk] <- statsFcn(Xkkjj) verbose && exit(verbose) } # for (jj ...) Xkk <- NULL # Not needed anymore verbose && exit(verbose) } # for (jj ...) # Not needed anymore X <- NULL verbose && cat(verbose, "Bootstrap statistics") verbose && str(verbose, S) # Reshape JxQx4 array to Jx(4*Q) matrix T <- wrap(S, map=list(1,NA), sep="_") colnames(T) <- gsub("(.*)_(.*)", "\\2_\\1", colnames(T)) # Append as new columns to the summary table stats <- cbind(stats, T) # Drop previously estimated values dups <- duplicated(colnames(stats), fromLast=TRUE) if (any(dups)) { stats <- stats[,!dups, drop=FALSE] } # Not needed anymore T <- dups <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Statistical sanity checks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (what == "segment" && B >= 100L) { verbose && enter(verbose, "Statistical sanity checks (iff B >= 100)") .stop_if_not(is.array(S)) # Find extreme quantiles probs <- dimnames(S)[[2L]] verbose && printf(verbose, "Available summaries: %s\n", paste(probs, collapse=", ")) probs <- grep("%", probs, fixed=TRUE, value=TRUE) S <- S[,probs,,drop=FALSE] probs <- gsub("%", "", probs, fixed=TRUE) probs <- as.double(probs) / 100 verbose && printf(verbose, "Available quantiles: %s\n", paste(probs, collapse=", ")) verbose && str(verbose, S) # Sanity check .stop_if_not(all(is.finite(probs))) # Is it possible to check? if (any(probs < 0.10) && any(probs > 0.90)) { tryCatch({ fields <- dimnames(S)[[3L]] for (kk in seq_along(fields)) { field <- fields[kk] verbose && enter(verbose, sprintf("Field #%d ('%s') of %d", kk, field, length(fields))) # Bootstrap statistics Skk <- S[,,kk, drop=FALSE] dim(Skk) <- dim(Skk)[-3L] # Sanity checks .stop_if_not(is.matrix(Skk)) range <- Skk[,c(1L,ncol(Skk)),drop=FALSE] # Segmentation means key <- sprintf("%sMean", field) segMean <- segs[[key]] # Segmentation counts cfield <- sprintf("%sNbrOfLoci", ifelse(field == "tcn", "tcn", "dh")) counts <- segs[,cfield,drop=TRUE] if (verbose) { for (rr in seq_len(length(segMean))) { printf(verbose, "Seg %3d. mean=%g, range=[%g,%g], n=%d\n", rr, segMean[rr], range[rr,1L], range[rr,2L], counts[rr]) } # for (rr ...) } # Compare only segments with enough data points keep <- (counts > 1L) range <- range[keep,,drop=FALSE] segMean <- segMean[keep] # Sanity checks .stop_if_not(all(range[,2L] + tol >= range[,1L], na.rm=TRUE)) .stop_if_not(all(segMean + tol >= range[,1L], na.rm=TRUE)) .stop_if_not(all(segMean - tol <= range[,2L], na.rm=TRUE)) verbose && exit(verbose) } # for (kk ...) }, error = function(ex) { # If an error, display the data, then throw the exception verbose && cat(verbose, "Tolerance (option 'PSCBS/sanityChecks/tolerance'): ", tol) verbose && print(verbose, segs) stop(ex) }) } else { verbose && cat(verbose, "Skipping. Not enough quantiles: ", paste(dimnames(S)[[2L]], collapse=", ")) } verbose && exit(verbose) } # if (B >= 100L) verbose && exit(verbose) stats } # summarizeSamples() # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'B': B <- Arguments$getInteger(B, range=c(1,Inf)) # Argument 'probs': probs <- Arguments$getNumerics(probs, range=c(0,1)) # Always estimate the default quantiles probs0 <- eval(formals(bootstrapTCNandDHByRegion.PairedPSCBS)$probs, enclos = baseenv()) probs <- unique(sort(c(probs, probs0))) # Argument 'statsFcn': if (is.null(statsFcn)) { statsFcn <- function(x) quantile(x, probs=probs, na.rm=TRUE) } # Argument 'what': what <- unique(match.arg(what, several.ok=TRUE)) # Argument 'force': force <- Arguments$getLogical(force) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # Argument '.debug': .debug <- Arguments$getLogical(.debug) verbose && enter(verbose, "Resample (TCN,DH) signals and re-estimate summaries for ", paste(what, collapse=" & ")) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract existing estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.element("segment", what)) { segs <- getSegments(fit) } if (is.element("changepoint", what)) { cps <- getChangePoints(fit) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Already done? # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - stats <- statsFcn(1) .stop_if_not(!is.null(names(stats))) nbrOfStats <- length(stats) statsNames <- names(stats) if (is.element("segment", what)) { tcnStatsNames <- sprintf("tcn_%s", names(stats)) dhStatsNames <- sprintf("dh_%s", names(stats)) c1StatsNames <- sprintf("c1_%s", names(stats)) c2StatsNames <- sprintf("c2_%s", names(stats)) allStatsNames <- c(tcnStatsNames, dhStatsNames, c1StatsNames, c2StatsNames) isDone <- is.element(allStatsNames, names(segs)) names(isDone) <- allStatsNames verbose && cat(verbose, "Already done?") verbose && print(verbose, isDone) # Not needed anymore allStatsNames <- tcnStatsNames <- dhStatsNames <- c1StatsNames <- c2StatsNames <- NULL if (!force && all(isDone)) { verbose && cat(verbose, "Already done. Skipping.") verbose && exit(verbose) return(fit) } } # The object to be returned fitB <- fit # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap (TCN,DH,C1,C2) segment mean levels # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.null(boot)) { boot <- bootstrapSegmentsAndChangepoints(fit, B=B, ..., force=force, .debug=.debug, verbose=verbose) } else { B <- dim(boot$segments)[2L] } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Summarizing segment (TCN,DH,C1,C2) mean levels # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.element("segment", what)) { segs <- summarizeSamples(boot$segments, statsFcn=statsFcn, stats=segs, what="segment", verbose=verbose) # Record statistics fitB$output <- segs segs <- NULL # Not needed anymore } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Summarizing change point (alpha, radius, manhattan, d1, d2) data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.element("changepoint", what)) { cps <- summarizeSamples(boot$changepoints, statsFcn=statsFcn, stats=cps, what="changepoint", verbose=verbose) # Record statistics fitB$changepoints <- cps cps <- NULL # Not needed anymore } # Not needed anymore fit <- boot <- NULL verbose && exit(verbose) fitB }, private=TRUE) # bootstrapTCNandDHByRegion() # \item{by}{A @character specifying whether DH should be calculated from # normalized ('betaTN') or non-normalized ('betaT') tumor BAFs.} # \item{seed}{(optional) A random seed.} # # # \value{ # Returns a named @list containing two @arrays of bootstrap samples. # These arrays also contains the original observation as the first # element before the actual bootstrap samples. # } setMethodS3("bootstrapSegmentsAndChangepoints", "PairedPSCBS", function(fit, B=1000L, by=c("betaTN", "betaT"), seed=NULL, force=FALSE, cache=FALSE, verbose=FALSE, .debug=FALSE, ...) { # Settings for sanity checks tol <- getOption("PSCBS/sanityChecks/tolerance", 0.0005) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'B': B <- Arguments$getInteger(B, range=c(1,Inf)) # Argument 'by': by <- match.arg(by) # Argument 'seed': if (!is.null(seed)) { seed <- Arguments$getInteger(seed) } # Argument '.cache': cache <- Arguments$getLogical(cache) # Argument 'force': force <- Arguments$getLogical(force) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } # Argument '.debug': .debug <- Arguments$getLogical(.debug) verbose && enter(verbose, "Bootstrapping (TCN,DH,C1,C2) segment mean levels") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Check for cached results # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - key <- list(method="bootstrapSegmentsAndChangepoints", class=class(fit)[1L], fit=fit, B=B, by=by, seed=seed) dirs <- c("PSCBS", "bootstrap") boot <- loadCache(key=key, dirs=dirs) if (!force && !is.null(boot)) { verbose && cat(verbose, "Found cached results. Skipping.") verbose && exit(verbose) return(boot) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Set the random seed # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (!is.null(seed)) { randomSeed("set", seed=seed, kind="L'Ecuyer-CMRG") on.exit(randomSeed("reset"), add=TRUE) verbose && printf(verbose, "Random seed temporarily set (seed=%d)\n", seed) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Extract data and estimates # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- getLocusData(fit) tcnSegRows <- fit$tcnSegRows dhSegRows <- fit$dhSegRows segs <- getSegments(fit) params <- fit$params # Sanity checks .stop_if_not(all(!is.na(data$chromosome) & !is.na(data$x))) # Sanity checks if (!params$joinSegments) { stop("Cannot bootstrap TCN and DH by segments unless PSCNs are segmented using joinSegments=TRUE.") } if (regexpr(",", params$flavor, fixed=TRUE) != -1L) { stop(sprintf("Cannot bootstrap TCN and DH by segments if PSCNs are segmented using flavor=\"%s\".", params$flavor)) } # Sanity check (same as above, but just in case) .stop_if_not(all(segs$tcnStart == segs$dhStart, na.rm=TRUE)) .stop_if_not(all(segs$tcnEnd == segs$dhEnd, na.rm=TRUE)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Find estimators # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get mean estimators used estList <- getMeanEstimators(fit, c("tcn", "dh")) avgTCN <- estList$tcn avgDH <- estList$dh estList <- NULL # Not needed anymore # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get signals # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Get (x,TCN,BAF) data chromosome <- data$chromosome x <- data$x CT <- data$CT betaT <- data[[by]] muN <- data$muN rho <- data$rho # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Classify each locus as (i) heterozygous SNP, (ii) homozygous SNP, # or (iii) non-polymorphic loci # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identifying heterozygous & homozygous SNPs and non-polymorphic loci") nbrOfLoci <- length(CT) verbose && cat(verbose, "Number of loci: ", nbrOfLoci) # Identify SNPs hasDH <- !is.null(rho) if (hasDH) { isHet <- !is.na(rho) isSnp <- isHet } else { isSnp <- (!is.na(muN) & !is.na(betaT)) isHet <- (isSnp & (muN == 1/2)) } snps <- which(isSnp) nonSNPs <- which(!isSnp) nbrOfSNPs <- sum(isSnp) nbrOfNonSNPs <- sum(!isSnp) verbose && cat(verbose, "Number of SNPs: ", nbrOfSNPs) verbose && cat(verbose, "Number of non-SNPs: ", nbrOfNonSNPs) # Sanity checks .stop_if_not(length(intersect(snps, nonSNPs)) == 0L) # Heterozygous SNPs hets <- which(isSnp & isHet) homs <- which(isSnp & !isHet) nbrOfHets <- length(hets) nbrOfHoms <- length(homs) if (!hasDH) { verbose && printf(verbose, "Number of heterozygous SNPs: %d (%.2f%%)\n", nbrOfHets, 100*nbrOfHets/nbrOfSNPs) verbose && printf(verbose, "Number of homozygous SNPs: %d (%.2f%%)\n", nbrOfHoms, 100*nbrOfHoms/nbrOfSNPs) } # Sanity checks .stop_if_not(length(intersect(hets, homs)) == 0L) .stop_if_not(nbrOfHets + nbrOfHoms == nbrOfSNPs) # Sanity checks .stop_if_not(length(isSnp) == nbrOfLoci) .stop_if_not(length(isHet) == nbrOfLoci) # Not needed anymore muN <- isSnp <- NULL verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Precalculate DH signals # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (is.null(rho)) { # Calculate DHs for heterozygous SNPs rho <- 2*abs(betaT - 1/2) # DH is by definition only defined for heterozygous SNPs. # For simplicity, we set it to be NA for non-heterozygous loci. rho[!isHet] <- NA_real_ data$rho <- rho } # Not needed anymore betaT <- isHet <- NULL # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Resample (TCN,DH) within each segments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - nbrOfSegments <- nrow(segs) # Allocate JxBx4 matrix M of bootstrap means dim <- c(nbrOfSegments, B, 4L) dimnames <- list(NULL, NULL, c("tcn", "dh", "c1", "c2")) M <- array(NA_real_, dim=dim, dimnames=dimnames) verbose && str(verbose, M) # Identify all loci with non-missing signals idxsCT <- which(!is.na(CT)) idxsRho <- which(!is.na(rho)) # Vectorized pre-adjustments for (field in c("tcnNbrOfLoci", "dhNbrOfLoci")) { counts <- segs[[field]] counts[is.na(counts)] <- 0L segs[[field]] <- counts } hasTcnLoci <- (is.finite(tcnSegRows[,1L]) & is.finite(tcnSegRows[,2L])) hasDhLoci <- (is.finite(dhSegRows[,1L]) & is.finite(dhSegRows[,2L])) # Identify "splitter" segments which have no data chrs <- segs[["chromosome"]] tcnIds <- segs[["tcnId"]] dhIds <- segs[["dhId"]] tcnMeans <- segs[["tcnMean"]] dhMeans <- segs[["dhMean"]] isSplitter <- (is.na(chrs) & is.na(tcnIds) & is.na(dhIds)) # Get all segment indices except for "splitters" jjs <- seq_len(nbrOfSegments) jjs <- jjs[!isSplitter] for (jj in jjs) { chr <- chrs[jj] tcnId <- tcnIds[jj] dhId <- dhIds[jj] verbose && enter(verbose, sprintf("Segment #%d (chr %d, tcnId=%d, dhId=%d) of %d", jj, chr, tcnId, dhId, nbrOfSegments)) # Sanity check if (.debug) .stop_if_not(!is.na(chr) && !is.na(tcnId) && !is.na(dhId)) # Get the segment data segJJ <- segs[jj,,drop=FALSE] verbose && print(verbose, segJJ) nbrOfTCNs <- segJJ[,"tcnNbrOfLoci"] nbrOfDHs <- segJJ[,"dhNbrOfLoci"] verbose && cat(verbose, "Number of TCNs: ", nbrOfTCNs) verbose && cat(verbose, "Number of DHs: ", nbrOfDHs) if (.debug) { .stop_if_not(!is.na(nbrOfTCNs)) .stop_if_not(!is.na(nbrOfDHs)) } tcnSegRowJJ <- unlist(tcnSegRows[jj,], use.names=FALSE) dhSegRowJJ <- unlist(dhSegRows[jj,], use.names=FALSE) # Indices of all loci if (hasTcnLoci[jj]) { idxsAll <- tcnSegRowJJ[1L]:tcnSegRowJJ[2L] } else { idxsAll <- 0L } verbose && str(verbose, idxsAll) verbose && print(verbose, hpaste(idxsAll), level=-120) verbose && str(verbose, idxsCT) verbose && print(verbose, hpaste(idxsCT), level=-120) # Keep only loci with finite TCNs idxsAll <- intersect(idxsAll, idxsCT) verbose && str(verbose, idxsAll) verbose && print(verbose, hpaste(idxsAll), level=-120) # Sanity check if (length(idxsAll) != nbrOfTCNs) { verbose && str(verbose, setdiff(idxsCT, idxsAll)) stop("INTERNAL ERROR: length(idxsAll) != nbrOfTCNs: ", length(idxsAll), " != ", nbrOfTCNs) } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify loci used to calculate DH means # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identify loci used to bootstrap DH means") if (hasDhLoci[jj]) { idxsDH <- dhSegRowJJ[1L]:dhSegRowJJ[2L] idxsDH <- intersect(idxsDH, hets) # Drop missing values idxsDH <- intersect(idxsDH, idxsRho) } else { idxsDH <- 0L } verbose && cat(verbose, "Heterozygous SNPs to resample for DH:") verbose && str(verbose, idxsDH) # Sanity check if (.debug) .stop_if_not(length(idxsDH) == nbrOfDHs) verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Identify loci used to calculate TCN means # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Identify loci used to bootstrap TCN means") # Identify SNPs and non-SNPs idxsSNP <- intersect(snps, idxsAll) idxsNonSNP <- setdiff(idxsAll, idxsSNP) verbose && cat(verbose, "SNPs:") verbose && str(verbose, idxsSNP) verbose && cat(verbose, "Non-polymorphic loci:") verbose && str(verbose, idxsNonSNP) # Sanity check if (.debug) .stop_if_not(length(idxsSNP) + length(idxsNonSNP) == length(idxsAll)) # Identify heterozygous and homozygous SNPs idxsHet <- intersect(idxsSNP, hets) if (nbrOfHoms > 0) { idxsHom <- intersect(idxsSNP, homs) } else { ## Happens when only DH is available idxsHom <- integer(0L) } # Drop missing values idxsNonSNP <- intersect(idxsNonSNP, idxsCT) idxsHet <- intersect(idxsHet, idxsCT) idxsHom <- intersect(idxsHom, idxsCT) idxsHetNonDH <- setdiff(idxsHet, idxsDH) verbose && cat(verbose, "Heterozygous SNPs to resample for TCN:") verbose && str(verbose, idxsHet) verbose && cat(verbose, "Homozygous SNPs to resample for TCN:") verbose && str(verbose, idxsHom) verbose && cat(verbose, "Non-polymorphic loci to resample for TCN:") verbose && str(verbose, idxsNonSNP) verbose && cat(verbose, "Heterozygous SNPs with non-DH to resample for TCN:") verbose && str(verbose, idxsHetNonDH) # Note that length(idxsHetNonDH) may differ from zero in case CT is non-missing # but rho is missing, e.g. CT = sum(c(thetaA,thetaB), na.rm=TRUE) and # thetaB is missing. /HB 2010-12-01 idxsTCN <- sort(unique(c(idxsHet, idxsHom, idxsNonSNP))) verbose && cat(verbose, "Loci to resample for TCN:") verbose && str(verbose, idxsTCN) # Sanity check if (.debug) { .stop_if_not(length(idxsHet) + length(idxsHom) + length(idxsNonSNP) == nbrOfTCNs) .stop_if_not(length(intersect(idxsDH, idxsHetNonDH)) == 0L) .stop_if_not(length(idxsTCN) == nbrOfTCNs) } verbose && exit(verbose) # These numbers should be preserved when the resampling verbose && printf(verbose, "Number of (#hets, #homs, #nonSNPs): (%d,%d,%d)\n", length(idxsHet), length(idxsHom), length(idxsNonSNP)) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Sanity checks # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - if (nbrOfTCNs > 0L) { # Sanity check ys <- CT[idxsTCN] mu <- avgTCN(ys, na.rm=TRUE) dMu <- (mu - tcnMeans[jj]) if (abs(dMu) > tol) { str(list(nbrOfTCNs=nbrOfTCNs, tcnNbrOfLoci=segJJ$tcnNbrOfLoci, mu=mu, tcnMean=tcnMeans[jj], dMu=dMu, "abs(dMu)"=abs(dMu), "range(x[units])"=range(x[idxsTCN]))) stop(sprintf("INTERNAL ERROR: Incorrectly recalculated TCN mean for Segment #%d (chr %d, tcnId=%d, dhId=%d): %g != %g", jj, chr, tcnId, dhId, mu, tcnMeans[jj])) } } shouldHaveDHs <- (nbrOfDHs > 0L && !is.na(dhMeans[jj])) if (shouldHaveDHs) { # Sanity check ys <- rho[idxsDH] mu <- avgDH(ys, na.rm=TRUE) dMu <- (mu - dhMeans[jj]) if (abs(dMu) > tol) { str(list(nbrOfDHs=nbrOfDHs, dhNbrOfLoci=segJJ$dhNbrOfLoci, mu=mu, dhMean=dhMeans[jj], dMu=dMu, "abs(dMu)"=abs(dMu), "range(x[units])"=range(x[idxsDH]))) stop(sprintf("INTERNAL ERROR: Incorrectly recalculated DH mean for Segment #%d (chr %d, tcnId=%d, dhId=%d): %g != %g", jj, chr, tcnId, dhId, mu, dhMeans[jj])) } } # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap while preserving (#hets, #homs, #nonSNPs) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Bootstrapping while preserving (#hets, #homs, #nonSNPs)") verbose && cat(verbose, "Number of bootstrap samples: ", B) if (!shouldHaveDHs) { idxsHetNonDH <- idxsDH } nHoms <- length(idxsHom) nNonSNPs <- length(idxsNonSNP) nHetNonDHs <- length(idxsHetNonDH) # Defaults idxsDHBB <- NULL # Bootstrap B times for (bb in seq_len(B)) { # (1) Bootstrap DHs if (shouldHaveDHs) { # (a) Resample heterozygous SNPs (=> resampled DH units) idxsDHBB <- resample(idxsDH, size=nbrOfDHs, replace=TRUE) # Extract signals rhoBB <- rho[idxsDHBB] # Calculate bootstrap mean M[jj,bb,"dh"] <- avgDH(rhoBB, na.rm=TRUE) } # if (shouldHaveDHs) # (2) Bootstrap TCNs if (nbrOfTCNs > 0L) { # (a) Resample non-DH hets SNPs idxsHetNonDHBB <- resample(idxsHetNonDH, size=nHetNonDHs, replace=TRUE) idxsHetBB <- c(idxsDHBB, idxsHetNonDHBB) # (a) Resample homozygous SNPs if (nbrOfHoms > 0) { idxsHomBB <- resample(idxsHom, size=nHoms, replace=TRUE) } else { idxsHomBB <- integer(0L) } # (b) Resample non-SNPs idxsNonSNPBB <- resample(idxsNonSNP, size=nNonSNPs, replace=TRUE) # (c) Resampled TCN units idxsTCNBB <- c(idxsHetBB, idxsHomBB, idxsNonSNPBB) # Sanity check if (.debug) { .stop_if_not(length(intersect(idxsDHBB, idxsHetNonDHBB)) == 0L) .stop_if_not(length(intersect(idxsHetBB, idxsHomBB)) == 0L) .stop_if_not(length(intersect(idxsHetBB, idxsNonSNPBB)) == 0L) .stop_if_not(length(intersect(idxsHomBB, idxsNonSNPBB)) == 0L) } # Extract signals CTBB <- CT[idxsTCNBB] # Calculate bootstrap mean M[jj,bb,"tcn"] <- avgTCN(CTBB, na.rm=TRUE) } # if (nbrOfTCNs > 0L) } # (for bb ...) verbose && exit(verbose) verbose && exit(verbose) } # for (jj ...) verbose && cat(verbose, "Bootstrapped segment mean levels") verbose && str(verbose, M) # Sanity check .stop_if_not(all(!is.nan(M))) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Add (C1,C2) bootstrap mean levels # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Calculating (C1,C2) mean levels from (TCN,DH) mean levels") C1 <- (1-M[,,"dh", drop=FALSE]) * M[,,"tcn", drop=FALSE] / 2 C2 <- M[,,"tcn", drop=FALSE] - C1 M[,,"c1"] <- C1 M[,,"c2"] <- C2 verbose && str(verbose, M) # Sanity check .stop_if_not(dim(M)[1L] == nbrOfSegments) .stop_if_not(all(!is.nan(M))) # Not needed anymore C1 <- C2 <- NULL verbose && exit(verbose) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap polar (alpha,radius,manhattan) for change points # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - verbose && enter(verbose, "Calculating polar (alpha,radius,manhattan) for change points") C <- M[,,c("c1","c2"), drop=FALSE] # Calculate difference # (will be empty if nbrOfSegments == 1, but that's ok/intended) D <- C[-nbrOfSegments,,, drop=FALSE] - C[-1L,,, drop=FALSE] # Sanity check .stop_if_not(dim(D)[1L] == nbrOfSegments-1L) .stop_if_not(all(!is.nan(D))) C <- NULL # Not needed anymore # Allocate array dimnames <- dimnames(D) dimnames[[3L]] <- c("alpha", "radius", "manhattan", "d1", "d2") dim <- dim(D) dim[3L] <- length(dimnames[[3L]]) P <- array(NA_real_, dim=dim, dimnames=dimnames) .stop_if_not(dim(P)[1L] == nbrOfSegments-1L) if (nbrOfSegments >= 2L) { verbose && str(verbose, D) P[,,"alpha"] <- atan2(D[,,2], D[,,1]) # Changepoint angles in (0,2*pi) P[,,"radius"] <- sqrt(D[,,2]^2 + D[,,1]^2) P[,,"manhattan"] <- abs(D[,,2]) + abs(D[,,1]) P[,,"d1"] <- D[,,1] P[,,"d2"] <- D[,,2] } alpha <- D <- NULL # Not needed anymore verbose && cat(verbose, "Bootstrapped change points") verbose && str(verbose, P) # Sanity check .stop_if_not(dim(P)[1L] == nbrOfSegments-1L) .stop_if_not(all(!is.nan(P))) verbose && exit(verbose) boot <- list(segments=M, changepoints=P) # Cache? if (cache) { saveCache(boot, key=key, dirs=dirs) verbose && cat(verbose, "Saved results to cache.") } verbose && exit(verbose) boot }, private=TRUE) # bootstrapSegmentsAndChangepoints() setMethodS3("findBootstrapSummaries", "PairedPSCBS", function(fit, what=c("segment", "changepoint"), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'what': what <- match.arg(what) if (what == "segment") { data <- getSegments(fit) } else if (what == "changepoint") { data <- getChangePoints(fit) } grep("^[^_]+_[^_]+$", colnames(data), value=TRUE) }, protected=TRUE) # findBootstrapSummaries() setMethodS3("hasBootstrapSummaries", "PairedPSCBS", function(fit, ...) { fields <- findBootstrapSummaries(fit, ...) (length(fields) > 0L) }) setMethodS3("clearBootstrapSummaries", "PairedPSCBS", function(fit, what=c("segment", "changepoint"), ..., verbose=FALSE) { # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'what': what <- unique(match.arg(what, several.ok=TRUE)) # Argument 'verbose': verbose <- Arguments$getVerbose(verbose) if (verbose) { pushState(verbose) on.exit(popState(verbose)) } verbose && enter(verbose, "Clearing bootstrap summaries") whats <- what for (what in whats) { verbose && enter(verbose, sprintf("Clearing %ss", what)) fields <- findBootstrapSummaries(fit, what=what, ...) if (what == "segment") { data <- getSegments(fit) data <- data[,!is.element(colnames(data), fields)] fit$output <- data } else if (what == "changepoint") { data <- getChangePoints(fit) data <- data[,!is.element(colnames(data), fields)] fit$changepoints <- data } # Sanity check fields <- findBootstrapSummaries(fit, what=what, ...) .stop_if_not(length(fields) == 0L) data <- fields <- NULL # Not needed anymoew verbose && exit(verbose) } # for (what ...) verbose && exit(verbose) fit }, protected=TRUE) # clearBootstrapSummaries() ############################################################################## # HISTORY # 2013-10-22 # o SPEEDUP: Added argument 'cache' to bootstrapSegmentsAndChangepoints(), # which caches the results to file if cache=TRUE. # 2013-10-21 # o Added find-, has- and clearBootstrapSummaries(). # o Added argument 'what' to bootstrapTCNandDHByRegion(). # o BUG FIX: The new bootstrapSegmentsAndChangepoints() would give # "Error in D[, , 2] : incorrect number of dimensions" if bootstrapping # was done on a single change point (==two segments). # 2013-10-20 # o Now utilizing new getChangePoints(). # o Now calculating change-point angles in (0,2*pi) using atan2(). # o Added bootstrapSegmentsAndChangepoints(), which was extract from # internal code of bootstrapTCNandDHByRegion(). The latter now # utilizes the former. # o BUG FIX: bootstrapTCNandDHByRegion() did not identify segment # "splitters" as intended. This has had no impact on the results. # 2013-04-23 # o SPEEDUP: Made bootstrapTCNandDHByRegion() much faster by adding # use.names=FALSE to two internal unlist() statements. # 2013-04-22 # o Added argument 'probs' to bootstrapTCNandDHByRegion(). # 2013-04-09 # o Added Rdoc comments. # 2013-02-09 # o BUG FIX: bootstrapTCNandDHByRegion() for PairedPSCBS did not bootstrap # for all available loci when calculating total CNs statistics, iff # the segment had been called run-of-homozygosity (ROH). # Thanks to Oscar Rueda at the Cancer Research UK Cambridge Institute # for reporting on this. # 2013-02-07 # o Improved some verbose outputs of bootstrapTCNandDHByRegion(). # 2013-01-15 # o Now bootstrapTCNandDHByRegion() uses the params$avgTCN and params$avgDH # estimators, iff given. # 2012-11-05 # o GENERALIZATION: Now bootstrapTCNandDHByRegion() works for more "flavors", # including the default ('tcn') used by segmentByNonPairedPSCBS(). # 2012-09-20 # o SPEEDUP: By default bootstrapTCNandDHByRegion() for PairedPSCBS no # longer do sanity checks within the bootstrap loop. This significantly # speed up the method. To run checks, use argument .debug=TRUE. # 2012-02-26 # o BUG FIX: bootstrapTCNandDHByRegion() for PairedPSCBS would resample # from a subset of the intended TCNs, iff the DH mean was non-finite # while there were still heterozygous SNPs. This introduced a bias in # the estimates, which was neglectable for large segments, but for very # small segments (a few loci) it could be relatively large. # 2012-02-24 # o BUG FIX: bootstrapTCNandDHByRegion(..., force=TRUE) for PairedPSCBS # would give an error iff previous bootstrap estimates already existed. # o Added argument 'force' to bootstrapTCNandDHByRegion(). # 2011-11-26 # o Now bootstrapTCNandDHByRegion() for PairedPSCBS preserves NAs for DH # and (C1,C2) quantiles, if the DH mean level is NA, which can happen # when a segment is called ROH. # o An internal sanity check of bootstrapTCNandDHByRegion() for PairedPSCBS # would give an error if DH mean levels had been set to NA for segments # called ROH. # 2011-11-24 # o BUG FIX: bootstrapTCNandDHByRegion() for PairedPSCBS would give # an error, if a segment did not have any TCN signals, which can # occur when known segments are specified for Paired PSCBS. # 2011-08-08 # o Moved the sanity checks that tests the TCN and DH "segRows" from the # bootstrapTCNandDHByRegion() to segmentByPairedPSCBS(). This is the # first step to fix a failure in the sanity checks that could happend # iff one first run dropSegmentationOutliers(). # 2011-06-14 # o Updated code to recognize new column names. # 2011-05-29 # o Renamed options to reflect new package name. # 2010-12-03 # o BUG FIX: In rare cases the bootstrap sanity checks can indeed produce # an invalid 'range', more precisely where (range[,2] >= range[,1]) is # not true. This can happen if there is no variation in the bootstrap # estimates. Beause of this we allow for some tolerance. # 2010-12-02 # o Now bootstrapTCNandDHByRegion() uses option # "psCBS/sanityChecks/tolerance". # 2010-12-01 # o BUG FIX: bootstrapTCNandDHByRegion() did not always exclude the correct # loci. # 2010-11-27 # o BUG FIX: bootstrapTCNandDHByRegion() would incorrectly include # non-polymorphic loci in the set of homozygous SNPs during resampling. # 2010-11-26 # o BUG FIX: The statistical sanity checks of the bootstrap estimates would # give an error when only single-sided bootstrap confidence interval was # calculated. # 2010-11-23 # o ROBUSTNESS: Added more sanity checks to bootstrapTCNandDHByRegion(). # o WORKAROUND: The precision of the mean levels of DNAcopy::segment() # is not great enough to always compare it to that of R's estimates. # o BUG FIX: bootstrapTCNandDHByRegion() would give an error if there was # only one segment. # 2010-11-22 # o BUG FIX: The DH segmentation and bootstrap incorrectly included # missing values, when subseting. # o BUG FIX: Some sanity checks were incorrect. # o BUG FIX: bootstrapTCNandDHByRegion() for PairedPSCBS would not correctly # detect if bootstrap results are already available. # 2010-11-21 # o Added argument 'seed'. # o Added bootstrapTCNandDHByRegion() for PairedPSCBS. # o Created from PairedPSCBS.BOOT.R. ############################################################################## PSCBS/vignettes/0000755000176200001440000000000015000517067013135 5ustar liggesusersPSCBS/vignettes/PairedPSCBS.tex.rsp0000644000176200001440000005376114564051545016505 0ustar liggesusers<%@meta language="R-vignette" content="-------------------------------- DIRECTIVES FOR R: %\VignetteIndexEntry{Parent-specific copy-number segmentation using Paired PSCBS} %\VignetteAuthor{Henrik Bengtsson} %\VignetteKeyword{copy numbers} %\VignetteKeyword{allele specific} %\VignetteKeyword{parent specific} %\VignetteKeyword{genomic aberrations} %\VignetteEngine{R.rsp::rsp} --------------------------------------------------------------------"%> <% t0 <- Sys.time() %> <% R.utils::use("R.utils") # RSP specific R.rsp <- R.oo::Package("R.rsp") withCapture <- R.utils::withCapture options("withCapture/newline"=FALSE) options(str=strOptions(strict.width="cut")) options(width=85) options(digits=3) # Graphics use("R.devices") options("devEval/args/field"="fullname") # Preferred for LaTeX devOptions("png", width=840) # Analysis use("PSCBS") PSCBS <- R.oo::Package("PSCBS") fixLocations <- function(fit, ...) { for (key in grep("(end|start)$", colnames(fit$output))) { fit$output[[key]] <- as.integer(fit$output[[key]]) } fit } # fixLocations() %> \documentclass[letter]{article} \usepackage{xspace} \usepackage{alltt} \usepackage{xcolor} \usepackage{natbib} % \citep{}, \citet{} \usepackage{graphicx} \graphicspath{{figures/}} <%------------------------------------------------------------------- Assign PDF metadata -------------------------------------------------------------------%> % PDF metadata \usepackage{hyperref} % Ideally \hypersetup{hidelinks}, but for backward compatibility: \hypersetup{pdfborder={0 0 0}} \hypersetup{ pdfauthor={<%@meta name="author"%>}, pdftitle={<%@meta name="title"%>}, pdfsubject={}, pdfkeywords={<%@meta name="keywords"%>}, pdfproducer={R.rsp v<%=R.rsp$version%> by <%=R.rsp$author%>} } % Page margins \addtolength{\oddsidemargin}{-0.5in} \addtolength{\evensidemargin}{-0.5in} \addtolength{\textwidth}{1in} \addtolength{\topmargin}{-0.5in} \addtolength{\textheight}{1in} % Placement of floats \setcounter{bottomnumber}{2} \renewcommand{\topfraction}{1.0} \renewcommand{\bottomfraction}{1.0} \renewcommand{\textfraction}{0.0} \renewcommand{\floatpagefraction}{1.0} % Macros \newcommand{\keywords}[1]{{\footnotesize{\textbf{Keywords: }#1}}\xspace} \newcommand{\pkg}[1]{\textsl{#1}\xspace} \newcommand{\file}[1]{\textsl{#1}\xspace} \newcommand{\code}[1]{\texttt{#1}\xspace} \newcommand{\bs}{$\backslash$} \newcommand{\alphaTCN}{\alpha_{\textnormal{TCN}}\xspace} \newcommand{\alphaDH}{\alpha_{\textnormal{DH}}\xspace} \newcommand{\LOH}{\ensuremath{\textnormal{LOH}}\xspace} \newcommand{\AB}{\ensuremath{\textnormal{AB}}\xspace} \newenvironment{rspVerbatim}{\vspace{-\parskip}\begin{alltt}\color{blue}}{\end{alltt}} \newenvironment{escapeRspVerbatim}{\vspace{-\parskip}\begin{alltt}}{\end{alltt}} \title{<%@meta name="title"%>} \author{<%@meta name="author"%>} \date{<%=format(as.Date(PSCBS$date), format="%B %d, %Y")%>} \begin{document} \maketitle \begin{abstract} The Paired Parent-Specific Circular Binary Segmentation (Paired PSCBS) method partitions a tumor genome into segments of constant parent-specific copy numbers (PSCNs) based on SNP DNA microarray data from a matched tumor-normal pair. The method also calls segments with run of homozygosity (ROH), segments in allelic balance (AB) and segments with loss of heterozygosity (LOH). Paired PSCBS was designed to work with data from any SNP microarray technology and generation, including Affymetrix and Illumina. This document shows how to use the \pkg{PSCBS} package to run Paired PSCBS on a tumor-normal pair. \end{abstract} \keywords{<%@meta name="keywords"%>} \begin{center} \emph{This vignette is distributed as part of the \pkg{PSCBS} package, which is available on CRAN (\url{https://cran.r-project.org/}). The authors very much appreciate feedback on this document.} \end{center} \clearpage \tableofcontents \clearpage <%------------------------------------------------------------------- BACKGROUND -------------------------------------------------------------------%> \section{Background} \label{secBackground} We will here use a small example data set to illustrate how to setup the data in a format suitable for Paired PSCBS, how to identify segments, how to call them, and how to plot and export the segmentation results. The statistical model and the algorithm behind Paired PSCBS is explained in detail in~\citet{OlshenA_etal_2011}. <%------------------------------------------------------------------- EXAMPLE -------------------------------------------------------------------%> \section{Preparing data to be segmented} The Paired PSCBS~\citep{OlshenA_etal_2011} method requires tumor-normal paired parent-specific copy-number (PSCN) signals. More precisely, it requires total copy-number (TCN) estimates for the tumor relative to the matched normal ($C_T$), allele B fractions (BAFs) for the tumor ($\beta_T$) and BAFs for the matched normal ($\beta_N$). The genomic locations of the loci in form of chromosome and physical position are also required. \subsection{Locus-level SNP copy-number signals} \label{secData} In this example we will use a small example data set part of the \pkg{PSCBS} package. It can be loaded as: <% fullname <- "PairedPSCBS,exData,chr01" %> \begin{verbatim} <%=withCapture({ data <- PSCBS::exampleData("paired.chr01") str(data) })%> \end{verbatim} In additional to the mandatory fields (\code{chromosome}, \code{x}, \code{CT}, \code{betaT}, and \code{betaN}), this data set also contains TCNs for normal (\code{CN}) relative to a large pool of normal samples. The latter will not be used here. \subsection{Dropping TCN outliers} \label{secTCNOutliers} There may be some outliers among the TCNs. In CBS~\citep{OlshenA_etal_2004,VenkatramanOlshen_2007}, the authors propose a method for identifying outliers and then to shrink such values toward their neighbors ("smooth") before performing segmentation. At the time CBS was developed it made sense to not just to drop outliers because the resolution was low and every datapoint was valuable. With modern technologies the resolution is much higher and we can afford dropping such outliers, which can be done by: \begin{verbatim} <%=withCapture({ data <- dropSegmentationOutliers(data) })%> \end{verbatim} Dropping TCN outliers is optional. \section{Paired PSCBS segmentation} \subsection{Skipping centromeres and other large gaps} \label{secGaps} Like the CBS method, Paired PSCBS does not take the physical locations (in units of nucleotides) of the loci in to account when segmenting the data, only their relative ordering along the genome. This means that after having ordered the loci along genome, it will treat two "neighboring" loci that are on both sides of the centromere equally to two neighboring loci that are only a few hundred bases apart. This may introduce erroneous change points that appear to be inside the centromere. The same issues occur for other large gaps of the genome where there are no observed signals. To avoid this, although not mandatory, we will locate all gaps of the genome where there are no observed loci. As a threshold we will consider a region to be a "gap" if the distance between the two closest loci is greater than 1Mb. \begin{verbatim} <%=withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps })%> \end{verbatim} which shows that there is a 20.5Mb long gap between 121.0Mb and 141.5Mb on Chromosome~1. This is the centromere of Chromosome~1. It is not possible to specify "gaps" to the segmentation function. Instead they need to be given as part of a set of "known" segments, which is done as: \begin{verbatim} <%=withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments })%> \end{verbatim} Below, we will use this to tell Paired PSCBS to segment Chromosome~1 into three independent segments, where the first segment is from the beginning of the chromosome (hence '-Inf') to 120.1Mb, the second one from 120.1-141.5Mb (the above gap), and the third one is from 141.5Mb to the end of the chromosome (hence '+Inf'). Just as Paired PSCBS segments chromosomes independently of each other, it also segments priorly known segments independently of each other. Specifying known segments is optional. \subsection{Identifying PSCN segments} We are now ready to segment the locus-level PSCN signals. This is done by\footnote{We fix the random seed in order for the results of this vignette to be numerically reproducible.}: \begin{verbatim} <%=withCapture({ fit <- segmentByPairedPSCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) })%> \end{verbatim} Note that this may take several minutes when applied to whole-genome data. The above call will also normalize the tumor BAFs using the TumorBoost normalization method~\citep{BengtssonH_etal_2010} (without preserving the relative scale for homozygous and heterozygous BAFs; in a future version, this will be the default). If this has already been done or the tumor signals have been normalized by other means, the TumorBoost step can be skipped by setting argument \code{tbn=FALSE}. The result of the segmentation is a set of segments identified to have the same underlying PSCN levels. In this particular case, <%=nbrOfSegments(fit)%> PSCN segments were found: <% fit <- fixLocations(fit) %> \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> Note that Segment~\#<%=which(segs$tcnNbrOfLoci == 0)%> has no mean-level estimates. It is because it corresponds to the centromere (the gap) that was identified above. Paired PSCBS did indeed try to segment it, but since there are no data points, all estimates are missing values. Similarly, for Segment~\#<%=which(segs$dhNbrOfLoci == 0)%> the DH and minor and major CNs mean estimates are all missing values. This is because, Paired PSCBS identified that segment by first segmenting the TCN signals by themselves, and after which it tried to segment the DH signals within that segment. Since there are no heterozygous SNPs in the segment, there are no DH signals, and hence there is no DH mean estimate. \subsection{Displaying genomic PSCN profiles} To plot the PSCN segmentation results, do: \begin{verbatim} plotTracks(fit) \end{verbatim} which by default displays three panels containing TCN, decrease of heterozygosity (DH), and minor and major CNs as in Figure~\ref{figTracks}. To plot only one panel with TCN and minor and major CNs and zoom in on a particular region, do (not shown): \begin{verbatim} plotTracks(fit, tracks="tcn,c1,c2", xlim=c(120,244)*1e6) \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fit)[1L], "tracks"), aspectRatio=0.6, { plotTracks(fit) })%>}} \end{center} \caption{PSCN segments identified by Paired PSCBS. \textbf{Top}: The TCN signals with the TCN mean levels (purple). \textbf{Middle}: The DH signals with the DH mean levels (orange). \textbf{Bottom}: The TCN signals with the minor CN ($C_1$; blue), the major CN ($C_2$; red) and the TCN ($C=C_1+C_2$; purple) mean levels. } \label{figTracks} \end{figure} \section{Calling segments} The calling algorithms for allelic balance (AB) and loss of heterozygosity (LOH) are based on quantile estimates of the different mean levels. These estimates are obtained using non-parametric bootstrap techniques. For more details, see~\citet{OlshenA_etal_2011}. After the Paired PSCBS method was published, we have added methods for calling run of homozygosity (ROH) and neutral total copy number (NTCN). \emph{The ROH and NTCN calling methods should be considered under development until further notice, meaning they and their results may change without notice.} \subsection{Calling segments with run of homozygosity (ROH)*} \emph{Please note that this method is under development. This means that it may change without further notice.} A region has a run of homozygotes (ROH) if all of its SNPs are homozygous (in the normal). Since such a region has no heterozyous SNPs, its decrease in heterozygosity (DH) is undefined. Likewise, the minor and major copy numbers are unknown. However, if there are genotyping errors within an ROH region, we will obtain a non-missing DH mean level and hence also finite minor and major CNs. In order to adjust for these faulty estimates, we test if the identified segments are ROHs or not by: \begin{verbatim} <%=withCapture({ fit <- callROH(fit, verbose=-10) })%> \end{verbatim} This will also set the corresponding DH and minor and major CN mean levels to NA. The total CN mean levels are not affected by the ROH call. \subsubsection{Tuning parameters} For each segment, the test for ROH calculates the fraction of SNPs that are called heterozygous. If the fraction of heterozygotes is smaller than a threshold, the segmented is called ROH, otherwise not. The default threshold is 1/12. To use a different threshold, set argument \code{delta} to a scalar in $[0,1]$. For example, using \code{callROH(fit, delta=1/30)} makes the ROH caller more conservative.\footnote{It is our plan to replace this basic test with a bionomial test.} \subsection{Calling segments in allelic balance (AB)} The AB caller tests whether the DH level of a segment is small enough to be considered zero, which means that the minor and the major CNs are equal, i.e. the segment is in allelic balance. To call the AB state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callAB(fit, verbose=-10) })%> \end{verbatim} Because the caller utilizes bootstrapping techniques, calling AB may take some time if there is a large number of segments. Segments already called ROH will not be called for AB, and their AB statuses will have a missing value (\code{NA}). \subsubsection{Tuning parameters} The AB caller tests whether a segment's DH is zero or not, by comparing its DH level (or more precisely, the $5\%$ quantile of its bootstrapped DH mean level) to a threshold. This threshold will be a function of the noise level, because the noisier the BAF signals (and hence the DH signals), the greater the bias of the DH mean level for segments in AB will be. Because of this, the threshold is chosen from data by estimating the noise level of the DH signals near zero. Further rationales and details are given in~\citet{OlshenA_etal_2011}. The AB threshold can be estimated explicitly and used in the caller as \begin{verbatim} deltaAB <- estimateDeltaAB(fit, scale=1) fit <- callAB(fit, delta=deltaAB) \end{verbatim} By decreasing argument \code{scale} (a positive scalar), a smaller threshold will be obtained resulting in a more conservative AB caller. \subsection{Calling segments with loss of heterozygosity (LOH)} The LOH caller tests whether the minor CN level of a segment is large enough to be considered non-zero, which means that the segment is \emph{not} in LOH. To call the LOH state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callLOH(fit, verbose=-10) })%> \end{verbatim} Note that in order to call LOH, one has to call allelic balance first. Since the bootstrapping was already done in the AB caller, it is not repeated here, which is why calling LOH is faster than calling AB. Analogously to the AB caller, segments already called ROH will not be called for LOH, and their LOH statuses will have a missing value (\code{NA}). Segments already called AB will be called non-LOH, because AB and LOH are exclusively mutual states. \subsubsection{Tuning parameters} The LOH caller tests whether a segment's minor CN is non-zero or not, by comparing its minor CN level (or more precisely, the $95\%$ quantile of its bootstrapped minor CN mean level) to a threshold. This threshold will, among other components, be a function of normal contamination, i.e. the greater the fraction of normal cells is the greater the threshold needs to be in order to call LOH in the tumor cells. Because of this, the threshold is chosen from data as the midpoint of the estimated levels of minor CNs zero and one, which in turn is a function of the normal contamination. For details on the definition of LOH and details on the LOH caller, see~\citet{OlshenA_etal_2011}. The LOH threshold can be estimated explicitly and used as: \begin{verbatim} deltaLOH <- estimateDeltaLOH(fit, midpoint=1/2) fit <- callLOH(fit, delta=deltaLOH) \end{verbatim} By decreasing argument \code{midpoint} in $[0,1]$, a smaller threshold will be obtained resulting in a more conservative LOH caller. \subsection{Calling segments with neutral total copy number (NTCN)*} \emph{Please note that this method is under development. This means that it may change without further notice.} The neutral total copy number (NTCN) caller tests whether the total CN level of a segment is neutral (e.g. diploid) or not. To call the NTCN state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callNTCN(fit, verbose=-10) })%> \end{verbatim} \subsubsection{Tuning parameters} The NTCN caller identifies segments which TCN mean levels (or more precisely, which $95\%$ confidence intervals) are within a given "acceptance" region. This acceptance region is determined by the $95\%$ confidence interval of an initial set of AB segments identified to be copy neutral and then expanded by half a TCN unit length. The true length of half a total copy number unit is specified by the argument \code{delta} to \code{callNTCN()}. Its length should be a function of the overall background signals (which includes normal contamination and more), such that the width of the acceptance region becomes smaller when the background increases. The background signal (\code{kappa}) and \code{delta} can be estimated explicitly as: \begin{verbatim} kappa <- estimateKappa(fit) deltaCN <- estimateDeltaCN(fit, scale=1, kappa=kappa) fit <- callNTCN(fit, delta=deltaCN, verbose=-10) \end{verbatim} By decreasing the tuning parameter \code{scale} (a positive scalar), a smaller acceptance region will be obtained, which results in a more conservative CN caller. \subsection{Results from calling ROH, AB, LOH and NTCN} All calls are appended to the segmentation results as logical columns: \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> \section{Saving results} \subsection{Writing segments to a tab-delimited text file} To write the PSCN segmentation results to file, do: \begin{verbatim} pathname <- writeSegments(fit, name="MySample", simplify=TRUE) \end{verbatim} With \code{simplify=FALSE} (default) quantile estimates of the different mean levels will also be written, which roughly doubles the file size. \section{Experimental} In this section we illustrate some of the ongoing and future work that will be contained in the PSCBS package. Please be aware that these methods are very much under construction, possibly incomplete and in the worst case, even incorrect. \subsection{Less biased Decrease of Heterozygosity (DH) estimates} The DH mean levels of the segments are estimated as the sample mean of the DH signals within each segment. Since DH signals are by definition truncated at zero, the mean level estimates will always be greater than zero even if the true underlying DH is exactly zero. An additional bias is introduced because the distribution of the DH signals is skewed for small DHs, causing the sample mean estimate to be biased. A less biased estimate can be obtained by using the median estimator. To use the median estimator for DH mean levels, specify argument \code{avgDH="median"} to the \code{segmentByPairedPSCBS()} call. Because the DH mean levels will be less biased, the $(C_1,C_2)$ mean level estimates will also be less biased, e.g. they will be closer to each other for segments that are in allelic balance. \subsection{Pruning segmentation profile} By applying hierarchical clustering on the segment means, it is possible to prune the PSCN profile such that change points with very small absolute changes are dropped. If change points are dropped this way, this results in a smaller number of segments, which are hence longer on average. To prune Paired PSCBS segmentation results this way, do: \begin{verbatim} <%=withCapture({ fitP <- pruneByHClust(fit, h=0.25, verbose=-10) })%> \end{verbatim} The result of this is shown in Figure~\ref{figTracksPruned}. \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fitP)[1L], "pruned", "tracks"), aspectRatio=0.6, { plotTracks(fitP) })%>}} \end{center} \caption{Pruned PSCN segments plotted as in Figure~\ref{figTracks}.} \label{figTracksPruned} \end{figure} In the current implementation, any segment calls and quantile mean levels estimates previously are dropped when pruning. \subsection{Report generation} A multipage PDF report that contains both whole-genome and per-chromosome summaries and figures can be generated by: \begin{verbatim} > report(fit, sampleName="PairedPSCBS", studyName="PSCBS-Ex", verbose=-10) \end{verbatim} By default, the reports are written to directory \code{reports//} under the current working directory. In addition to the PDF, that directory also contains subdirectory \code{figures/} holding all generated figure files (e.g. PNGs and PDFs) for easy inclusion elsewhere. <%------------------------------------------------------------------- REFERENCES -------------------------------------------------------------------%> \bibliographystyle{natbib} \bibliography{PSCBS} <%------------------------------------------------------------------- APPENDIX -------------------------------------------------------------------%> \clearpage \section*{Appendix} \subsection*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using \code{rfile()} of the R.rsp package. Total processing time after RSP-to-R translation was <%=dt <- round(Sys.time()-t0, digits=2)%> <%=attr(dt, "units")%>. \end{document} PSCBS/vignettes/natbib.bst0000644000176200001440000006316014564051545015124 0ustar liggesusers%% %% This is file `natbib.bst', generated %% on <1994/9/16> with the docstrip utility (2.2h). %% %% The original source files were: %% %% genbst.mbs (with options: `ay,nat,seq-lab,nm-rev,dt-beg,yr-par,vol-bf, %% volp-com,etal-it') %% ---------------------------------------- %% *** Personal bib style, PWD *** %% %% (Here are the specifications of the source file) %% \ProvidesFile{genbst.mbs}[1994/09/16 1.5 (PWD)] %% For use with BibTeX version 0.99a or later %% and with LaTeX 2.09 or 2e %%------------------------------------------------------------------- %% NOTICE: %% This file may be used for non-profit purposes. %% It may not be distributed in exchange for money, %% other than distribution costs. %% %% The author provides it `as is' and does not guarantee it in any way. %% %% Copyright (C) 1994 Patrick W. Daly %% Max-Planck-Institut f\"ur Aeronomie %% Postfach 20 %% D-37189 Katlenburg-Lindau %% Germany %% %% E-mail: %% SPAN-- nsp::linmpi::daly (note nsp also known as ecd1) %% Internet-- daly@linmpi.dnet.gwdg.de %%----------------------------------------------------------- %% \CharacterTable %% {Upper-case \A\B\C\D\E\F\G\H\I\J\K\L\M\N\O\P\Q\R\S\T\U\V\W\X\Y\Z %% Lower-case \a\b\c\d\e\f\g\h\i\j\k\l\m\n\o\p\q\r\s\t\u\v\w\x\y\z %% Digits \0\1\2\3\4\5\6\7\8\9 %% Exclamation \! Double quote \" Hash (number) \# %% Dollar \$ Percent \% Ampersand \& %% Acute accent \' Left paren \( Right paren \) %% Asterisk \* Plus \+ Comma \, %% Minus \- Point \. Solidus \/ %% Colon \: Semicolon \; Less than \< %% Equals \= Greater than \> Question mark \? %% Commercial at \@ Left bracket \[ Backslash \\ %% Right bracket \] Circumflex \^ Underscore \_ %% Grave accent \` Left brace \{ Vertical bar \| %% Right brace \} Tilde \~} %%--------------------------------------------------------------------- % This is an author-year citation style bibliography. As such, it is % non-standard LaTeX, and requires a special package file to function properly. % Such a package is natbib.sty by Patrick W. Daly % The form of the \bibitem entries is % \bibitem[Jones et al.(1990)]{key}... % \bibitem[Jones et al.(1990)Jones, Baker, and Smith]{key}... % The essential feature is that the label (the part in brackets) consists % of the author names, as they should appear in the citation, with the year % in parentheses following. There must be no space before the opening % parenthesis! % With natbib v5.3, a full list of authors may also follow the year. % In natbib.sty, it is possible to define the type of enclosures that is % really wanted (brackets or parentheses), but in either case, there must % be parentheses in the label. % The \cite command functions as follows: % \cite{key} ==>> Jones et al. (1990) % \cite[]{key} ==>> (Jones et al., 1990) % \cite[chap. 2]{key} ==>> (Jones et al., 1990, chap. 2) % \cite[e.g.][]{key} ==>> (e.g. Jones et al., 1990) % \cite[e.g.][p. 32]{key} ==>> (e.g. Jones et al., p. 32) % \citeauthor{key} Jones et al. % \citefullauthor{key} Jones, Baker, and Smith % \citeyear{key} 1990 %%--------------------------------------------------------------------- ENTRY { address author booktitle chapter edition editor howpublished institution journal key month note number organization pages publisher school series title type volume year } {} { label extra.label sort.label } INTEGERS { output.state before.all mid.sentence after.sentence after.block } FUNCTION {init.state.consts} { #0 'before.all := #1 'mid.sentence := #2 'after.sentence := #3 'after.block := } STRINGS { s t } FUNCTION {output.nonnull} { 's := output.state mid.sentence = { ", " * write$ } { output.state after.block = { add.period$ write$ newline$ "\newblock " write$ } { output.state before.all = 'write$ { add.period$ " " * write$ } if$ } if$ mid.sentence 'output.state := } if$ s } FUNCTION {output} { duplicate$ empty$ 'pop$ 'output.nonnull if$ } FUNCTION {output.check} { 't := duplicate$ empty$ { pop$ "empty " t * " in " * cite$ * warning$ } 'output.nonnull if$ } FUNCTION {fin.entry} { add.period$ write$ newline$ } FUNCTION {new.block} { output.state before.all = 'skip$ { after.block 'output.state := } if$ } FUNCTION {new.sentence} { output.state after.block = 'skip$ { output.state before.all = 'skip$ { after.sentence 'output.state := } if$ } if$ } FUNCTION {not} { { #0 } { #1 } if$ } FUNCTION {and} { 'skip$ { pop$ #0 } if$ } FUNCTION {or} { { pop$ #1 } 'skip$ if$ } FUNCTION {non.stop} { duplicate$ "}" * add.period$ #-1 #1 substring$ "." = } FUNCTION {new.block.checkb} { empty$ swap$ empty$ and 'skip$ 'new.block if$ } FUNCTION {field.or.null} { duplicate$ empty$ { pop$ "" } 'skip$ if$ } FUNCTION {emphasize} { duplicate$ empty$ { pop$ "" } { "{\em " swap$ * non.stop { "\/}" * } 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author format.full.names } if$ } FUNCTION {author.key.full} { author empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { author format.full.names } if$ } FUNCTION {editor.key.full} { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.full.names } if$ } FUNCTION {make.full.names} { type$ "book" = type$ "inbook" = or 'author.editor.key.full { type$ "proceedings" = 'editor.key.full 'author.key.full if$ } if$ } FUNCTION {output.bibitem} { newline$ "\bibitem[" write$ label write$ ")" make.full.names * "]{" * write$ cite$ write$ "}" write$ newline$ "" before.all 'output.state := } FUNCTION {n.dashify} { 't := "" { t empty$ not } { t #1 #1 substring$ "-" = { t #1 #2 substring$ "--" = not { "--" * t #2 global.max$ substring$ 't := } { { t #1 #1 substring$ "-" = } { "-" * t #2 global.max$ substring$ 't := } while$ } if$ } { t #1 #1 substring$ * t #2 global.max$ substring$ 't := } if$ } while$ } FUNCTION {word.in} { "In " } FUNCTION {format.date} { year 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change.case$ " edition" * } { edition "t" change.case$ " edition" * } if$ } if$ } INTEGERS { multiresult } FUNCTION {multi.page.check} { 't := #0 'multiresult := { multiresult not t empty$ not and } { t #1 #1 substring$ duplicate$ "-" = swap$ duplicate$ "," = swap$ "+" = or or { #1 'multiresult := } { t #2 global.max$ substring$ 't := } if$ } while$ multiresult } FUNCTION {format.pages} { pages empty$ { "" } { pages multi.page.check { "pages" pages n.dashify tie.or.space.connect } { "page" pages tie.or.space.connect } if$ } if$ } FUNCTION {format.vol.num.pages} { volume field.or.null bolden number empty$ 'skip$ { "(" number * ")" * * volume empty$ { "there's a number but no volume in " cite$ * warning$ } 'skip$ if$ } if$ pages empty$ 'skip$ { duplicate$ empty$ { pop$ format.pages } { ", " * pages n.dashify * } if$ } if$ } FUNCTION {format.chapter.pages} { chapter empty$ 'format.pages { type empty$ { "chapter" } { type "l" change.case$ } if$ chapter tie.or.space.connect pages empty$ 'skip$ { ", " * format.pages * } if$ } if$ } FUNCTION {format.in.ed.booktitle} { booktitle empty$ { "" } { editor empty$ { word.in booktitle emphasize * } { word.in format.in.editors * ", " * booktitle emphasize * } if$ } if$ } FUNCTION {format.thesis.type} { type empty$ 'skip$ { pop$ type "t" change.case$ } if$ } FUNCTION {format.tr.number} { type empty$ { "Technical Report" } 'type if$ number empty$ { "t" change.case$ } { number tie.or.space.connect } if$ } FUNCTION {format.article.crossref} { word.in "\cite{" * crossref * "}" * } FUNCTION {format.book.crossref} { volume empty$ { "empty volume in " cite$ * "'s crossref of " * crossref * warning$ word.in } { "Volume" volume tie.or.space.connect " of " * } if$ "\cite{" * crossref * "}" * } FUNCTION {format.incoll.inproc.crossref} { word.in "\cite{" * crossref * "}" * } FUNCTION {article} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { journal emphasize "journal" output.check format.vol.num.pages output } { format.article.crossref output.nonnull format.pages output } if$ new.block note output fin.entry } FUNCTION {book} { output.bibitem author empty$ { format.editors "author and editor" output.check editor format.key output } { format.authors output.nonnull crossref missing$ { "author and editor" editor either.or.check } 'skip$ if$ } if$ format.date "year" output.check new.block format.btitle "title" output.check crossref missing$ { format.bvolume output new.block format.number.series output new.sentence publisher "publisher" output.check address output } { new.block format.book.crossref output.nonnull } if$ format.edition output new.block note output fin.entry } FUNCTION {booklet} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.title "title" output.check new.block howpublished output address output new.block note output fin.entry } FUNCTION {inbook} { output.bibitem author empty$ { format.editors "author and editor" output.check editor format.key output } { format.authors output.nonnull crossref missing$ { "author and editor" editor either.or.check } 'skip$ if$ } if$ format.date "year" output.check new.block format.btitle "title" output.check crossref missing$ { format.bvolume output format.chapter.pages "chapter and pages" output.check new.block format.number.series output new.sentence publisher "publisher" output.check address output } { format.chapter.pages "chapter and pages" output.check new.block format.book.crossref output.nonnull } if$ format.edition output new.block note output fin.entry } FUNCTION {incollection} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { format.in.ed.booktitle "booktitle" output.check format.bvolume output format.number.series output format.chapter.pages output new.sentence publisher "publisher" output.check address output format.edition output } { format.incoll.inproc.crossref output.nonnull format.chapter.pages output } if$ new.block note output fin.entry } FUNCTION {inproceedings} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { format.in.ed.booktitle "booktitle" output.check format.bvolume output format.number.series output format.pages output address output new.sentence organization output publisher output } { format.incoll.inproc.crossref output.nonnull format.pages output } if$ new.block note output fin.entry } FUNCTION {conference} { inproceedings } FUNCTION {manual} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.btitle "title" output.check organization address new.block.checkb organization output address output format.edition output new.block note output fin.entry } FUNCTION {mastersthesis} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.btitle "title" output.check new.block "Master's thesis" format.thesis.type output.nonnull school "school" output.check address output new.block note output fin.entry } FUNCTION {misc} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.title output new.block howpublished output new.block note output fin.entry } FUNCTION {phdthesis} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.btitle "title" output.check new.block "Ph.D. thesis" format.thesis.type output.nonnull school "school" output.check address output new.block note output fin.entry } FUNCTION {proceedings} { output.bibitem format.editors output editor format.key output format.date "year" output.check new.block format.btitle "title" output.check format.bvolume output format.number.series output address output new.sentence organization output publisher output new.block note output fin.entry } FUNCTION {techreport} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block format.tr.number output.nonnull institution "institution" output.check address output new.block note output fin.entry } FUNCTION {unpublished} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block note "note" output.check fin.entry } FUNCTION {default.type} { misc } MACRO {jan} {"January"} MACRO {feb} {"February"} MACRO {mar} {"March"} MACRO {apr} {"April"} MACRO {may} {"May"} MACRO {jun} {"June"} MACRO {jul} {"July"} MACRO {aug} {"August"} MACRO {sep} {"September"} MACRO {oct} {"October"} MACRO {nov} {"November"} MACRO {dec} {"December"} MACRO {acmcs} {"ACM Computing Surveys"} MACRO {acta} {"Acta Informatica"} MACRO {cacm} {"Communications of the ACM"} MACRO {ibmjrd} {"IBM Journal of Research and Development"} MACRO {ibmsj} {"IBM Systems Journal"} MACRO {ieeese} {"IEEE Transactions on Software Engineering"} MACRO {ieeetc} {"IEEE Transactions on Computers"} MACRO {ieeetcad} {"IEEE Transactions on Computer-Aided Design of Integrated Circuits"} MACRO {ipl} {"Information Processing Letters"} MACRO {jacm} {"Journal of the ACM"} MACRO {jcss} {"Journal of Computer and System Sciences"} MACRO {scp} {"Science of Computer Programming"} MACRO {sicomp} {"SIAM Journal on Computing"} MACRO {tocs} {"ACM Transactions on Computer Systems"} MACRO {tods} {"ACM Transactions on Database Systems"} MACRO {tog} {"ACM Transactions on Graphics"} MACRO {toms} {"ACM Transactions on Mathematical Software"} MACRO {toois} {"ACM Transactions on Office Information Systems"} MACRO {toplas} {"ACM Transactions on Programming Languages and Systems"} MACRO {tcs} {"Theoretical Computer Science"} READ FUNCTION {sortify} { purify$ "l" change.case$ } INTEGERS { len } FUNCTION {chop.word} { 's := 'len := s #1 len substring$ = { s len #1 + global.max$ substring$ } 's if$ } FUNCTION {format.lab.names} { 's := s #1 "{vv~}{ll}" format.name$ s num.names$ duplicate$ #2 > { pop$ " " * "et~al." emphasize * } { #2 < 'skip$ { s #2 "{ff }{vv }{ll}{ jj}" format.name$ "others" = { " " * "et~al." emphasize * } { " and " * s #2 "{vv~}{ll}" format.name$ * } if$ } if$ } if$ } FUNCTION {author.key.label} { author empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { author format.lab.names } if$ } FUNCTION {author.editor.key.label} { author empty$ { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.lab.names } if$ } { author format.lab.names } if$ } FUNCTION {editor.key.label} { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.lab.names } if$ } FUNCTION {calc.label} { type$ "book" = type$ "inbook" = or 'author.editor.key.label { type$ "proceedings" = 'editor.key.label 'author.key.label if$ } if$ "(" * year duplicate$ empty$ { pop$ "????" } { purify$ #-1 #4 substring$ } if$ * 'label := } FUNCTION {sort.format.names} { 's := #1 'nameptr := "" s num.names$ 'numnames := numnames 'namesleft := { namesleft #0 > } { nameptr #1 > { " " * } 'skip$ if$ s nameptr "{vv{ } }{ll{ }}{ f{ }}{ jj{ }}" format.name$ 't := nameptr numnames = t "others" = and { "et al" * } { numnames #2 > nameptr #2 = and { "zzzzzz" * #1 'namesleft := } { t sortify * } if$ } if$ nameptr #1 + 'nameptr := namesleft #1 - 'namesleft := } while$ } FUNCTION {sort.format.title} { 't := "A " #2 "An " #3 "The " #4 t chop.word chop.word chop.word sortify #1 global.max$ substring$ } FUNCTION {author.sort} { author empty$ { key empty$ { "to sort, need author or key in " cite$ * warning$ "" } { key sortify } if$ } { author sort.format.names } if$ } FUNCTION {author.editor.sort} { author empty$ { editor empty$ { key empty$ { "to sort, need author, editor, or key in " cite$ * warning$ "" } { key sortify } if$ } { editor sort.format.names } if$ } { author sort.format.names } if$ } FUNCTION {editor.sort} { editor empty$ { key empty$ { "to sort, need editor or key in " cite$ * warning$ "" } { key sortify } if$ } { editor sort.format.names } if$ } FUNCTION {presort} { calc.label label sortify " " * type$ "book" = type$ "inbook" = or 'author.editor.sort { type$ "proceedings" = 'editor.sort 'author.sort if$ } if$ #1 entry.max$ substring$ 'sort.label := sort.label * " " * title field.or.null sort.format.title * #1 entry.max$ substring$ 'sort.key$ := } ITERATE {presort} SORT STRINGS { last.label next.extra } INTEGERS { last.extra.num } FUNCTION {initialize.extra.label.stuff} { #0 int.to.chr$ 'last.label := "" 'next.extra := #0 'last.extra.num := } FUNCTION {forward.pass} { last.label label = { last.extra.num #1 + 'last.extra.num := last.extra.num int.to.chr$ 'extra.label := } { "a" chr.to.int$ 'last.extra.num := "" 'extra.label := label 'last.label := } if$ } FUNCTION {reverse.pass} { next.extra "b" = { "a" 'extra.label := } 'skip$ if$ extra.label 'next.extra := label extra.label * 'label := } EXECUTE {initialize.extra.label.stuff} ITERATE {forward.pass} REVERSE {reverse.pass} FUNCTION {bib.sort.order} { sort.label " " * year field.or.null sortify * " " * title field.or.null sort.format.title * #1 entry.max$ substring$ 'sort.key$ := } ITERATE {bib.sort.order} SORT FUNCTION {begin.bib} { preamble$ empty$ 'skip$ { preamble$ write$ newline$ } if$ "\begin{thebibliography}{}" write$ newline$ } EXECUTE {begin.bib} EXECUTE {init.state.consts} ITERATE {call.type$} FUNCTION {end.bib} { newline$ "\end{thebibliography}" write$ newline$ } EXECUTE {end.bib} %% End of customized bst file PSCBS/vignettes/CBS.tex.rsp0000644000176200001440000003011114564051545015075 0ustar liggesusers<%@meta language="R-vignette" content="-------------------------------- DIRECTIVES FOR R: %\VignetteIndexEntry{Total copy-number segmentation using CBS} %\VignetteKeyword{copy numbers} %\VignetteKeyword{genomic aberrations} %\VignetteAuthor{Henrik Bengtsson} %\VignetteEngine{R.rsp::rsp} --------------------------------------------------------------------"%> <% t0 <- Sys.time() %> <% R.utils::use("R.utils") # RSP specific R.rsp <- R.oo::Package("R.rsp") withCapture <- R.utils::withCapture options("withCapture/newline"=FALSE) options(str=strOptions(strict.width="cut")) options(width=85) options(digits=3) # Graphics use("R.devices") options("devEval/args/field"="fullname") # Preferred for LaTeX devOptions("png", width=840) # Analysis use("PSCBS") PSCBS <- R.oo::Package("PSCBS") fixLocations <- function(fit, ...) { for (key in grep("(end|start)$", colnames(fit$output))) { fit$output[[key]] <- as.integer(fit$output[[key]]) } fit } # fixLocations() signalType <- "TCN" %> \documentclass[letter]{article} \usepackage{xspace} \usepackage{alltt} \usepackage{xcolor} \usepackage{natbib} % \citep{}, \citet{} \usepackage{graphicx} \graphicspath{{figures/}} <%------------------------------------------------------------------- Assign PDF metadata -------------------------------------------------------------------%> % PDF metadata \usepackage{hyperref} % Ideally \hypersetup{hidelinks}, but for backward compatibility: \hypersetup{pdfborder={0 0 0}} \hypersetup{ pdfauthor={<%@meta name="author"%>}, pdftitle={<%@meta name="title"%>}, pdfsubject={}, pdfkeywords={<%@meta name="keywords"%>}, pdfproducer={R.rsp v<%=R.rsp$version%> by <%=R.rsp$author%>} } % Page margins \addtolength{\oddsidemargin}{-0.5in} \addtolength{\evensidemargin}{-0.5in} \addtolength{\textwidth}{1in} \addtolength{\topmargin}{-0.5in} \addtolength{\textheight}{1in} % Placement of floats \setcounter{bottomnumber}{2} \renewcommand{\topfraction}{1.0} \renewcommand{\bottomfraction}{1.0} \renewcommand{\textfraction}{0.0} \renewcommand{\floatpagefraction}{1.0} % Macros \newcommand{\keywords}[1]{{\footnotesize{\textbf{Keywords: }#1}}\xspace} \newcommand{\pkg}[1]{\textsl{#1}\xspace} \newcommand{\file}[1]{\textsl{#1}\xspace} \newcommand{\code}[1]{\texttt{#1}\xspace} \newcommand{\bs}{$\backslash$} \newenvironment{rspVerbatim}{\vspace{-\parskip}\begin{alltt}\color{blue}}{\end{alltt}} \newenvironment{escapeRspVerbatim}{\vspace{-\parskip}\begin{alltt}}{\end{alltt}} \title{<%@meta name="title"%>} \author{<%@meta name="author"%>} \date{<%=format(as.Date(PSCBS$date), format="%B %d, %Y")%>} \begin{document} \maketitle \begin{abstract} The Circular Binary Segmentation (CBS) method partitions a genome into segments of constant total copy numbers (TCNs) based on DNA microarray data. The method also calls .... CBS was designed to work with data from any DNA microarray technology and generation, including Affymetrix and Illumina. This document shows how to use the \pkg{PSCBS} package to run CBS on a tumor sample. \end{abstract} \keywords{<%@meta name="keywords"%>} \begin{center} \emph{This vignette is distributed as part of the \pkg{PSCBS} package, which is available on CRAN (\url{https://cran.r-project.org/}). The authors very much appreciate feedback on this document.} \end{center} \clearpage \tableofcontents \clearpage <%------------------------------------------------------------------- BACKGROUND -------------------------------------------------------------------%> \section{Background} \label{secBackground} We will here use a small example data set to illustrate how to setup the data in a format suitable for CBS, how to identify segments, how to call them, and how to plot and export the segmentation results. The statistical model and the algorithm behind CBS is explained in detail in \citet{OlshenA_etal_2004, VenkatramanOlshen_2007}. <%------------------------------------------------------------------- EXAMPLE -------------------------------------------------------------------%> \section{Preparing data to be segmented} The CBS method requires total copy-number (TCN) estimates. More precisely, it requires TCN ratios for a sample of interest relative to a reference ($y$). The genomic location of the loci in form of chromosome and physical position are also required. \subsection{Locus-level total copy-number signals} \label{secData} In this example we will use a small example data set part of the \pkg{PSCBS} package. It can be loaded as: <% fullname <- "PairedPSCBS,exData,chr01" %> \begin{verbatim} <%=withCapture({ data <- PSCBS::exampleData("paired.chr01") data <- data[,c("chromosome", "x", "CT")] colnames(data)[3] <- "y" str(data) })%> \end{verbatim} In additional to the mandatory fields (\code{chromosome}, \code{x}, and \code{C} this data set also contains .... The latter will not be used here. \subsection{Dropping <%=signalType%> outliers} \label{secTCNOutliers} There may be some outliers among the <%=signalType%>s. In CBS~\citep{OlshenA_etal_2004,VenkatramanOlshen_2007}, the authors propose a method for identifying outliers and then to shrink such values toward their neighbors ("smooth") before performing segmentation. At the time CBS was developed it made sense to not just to drop outliers because the resolution was low and every datapoint was valuable. With modern technologies the resolution is much higher and we can afford dropping such outliers, which can be done by: \begin{verbatim} <%=withCapture({ data <- dropSegmentationOutliers(data) })%> \end{verbatim} Dropping <%=signalType%> outliers is optional. \section{CBS segmentation} \subsection{Skipping centromeres and other large gaps} \label{secGaps} The CBS method does not take the physical locations (in units of nucleotides) of the loci in to account when segmenting the data, only their relative ordering along the genome. This means that after having ordered the loci along genome, it will treat two "neighboring" loci that are on both sides of the centromere equally as two neighboring loci that are only few hundred bases apart. This may introduce erroneous change points that appears to be inside the centromere and biological impossible interpretation of the identified copy-number states. The same issues occur for other large gaps of the genome where there are no observed signals. To avoid this, although not mandatory, we will locate all gaps of the genome where there are no observed loci. As a threshold we will consider a region to be a "gap" if the distance between the two closest loci is greater than 1Mb. \begin{verbatim} <%=withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps })%> \end{verbatim} which shows that there is a 20.5Mb long gap between 121.0Mb and 141.5Mb on Chromosome~1. This is the centromere of Chromosome~1. Gaps cannot be specified directly. Instead they need to be give as part of a set of "known" segments, which is done as: \begin{verbatim} <%=withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments })%> \end{verbatim} Below, we will use this to tell CBS to segment Chromosome~1 in three independent segments, where the first segments is from the beginning of the chromosomes (hence '-Inf') to 120.1Mb, the second from 120.1-141.5Mb (the above gap), and the third is from 141.5Mb to the end of the chromosome (hence '+Inf'). Just as CBS segments chromosomes independently of each other, it also segments priorly known segments independently of each other. Specifying known segments is optional. \subsection{Identifying <%=signalType%> segments} We are now ready to segment the locus-level <%=signalType%> signals. This is done by\footnote{We fix the random seed in order for the results of this vignette to be exactly reproducible.}: \begin{verbatim} <%=withCapture({ fit <- segmentByCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) })%> \end{verbatim} Note that this may take several minutes when applied to whole-genome data. The result of the segmentation is a set of segments identified to have the same underlying <%=signalType%> levels. In this particular case, <%=nbrOfSegments(fit)%> <%=signalType%> segments were found: <% fit <- fixLocations(fit) %> \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> Note how Segment~\#<%=which(segs$nbrOfLoci == 0)%> has no mean-level estimates. It is because it corresponds to the centromere (the gap) that was identified above. CBS did indeed try to segment it, but since there are no data points, all estimates are missing values. \subsection{Displaying genomic <%=signalType%> profiles} To plot the <%=signalType%> segmentation results, do: \begin{verbatim} plotTracks(fit) \end{verbatim} which displays <%=signalType%> as in Figure~\ref{figTracks}. To zoom in on a particular region, do: \begin{verbatim} plotTracks(fit, xlim=c(120,244)*1e6) \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fit)[1L], "tracks"), aspectRatio=0.35, { plotTracks(fit) })%>}} \end{center} \caption{Segments identified by CBS. The <%=signalType%> signals with the <%=signalType%> mean levels (purple). } \label{figTracks} \end{figure} \section{Calling segments} TBA. <%--- \subsection{Results from calling <%=signalType%> states} All calls are appended to the segmentation results as logical columns: \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> ---%> \section{Saving results} \subsection{Writing segments to a tab-delimited text file} To write the <%=signalType%> segmentation results to file, do: \begin{verbatim} pathname <- writeSegments(fit, name="MySample", simplify=TRUE) \end{verbatim} \section{Experimental} In this section we illustrate some of the ongoing and future work of the PSCBS package. Please be aware that these methods are very much under construction, possibly incomplete and in worst case even incorrect. \subsection{Pruning segmentation profile} By using hierarchical cluster of the segment means it is possible to prune the <%=signalType%> profile such that change points with very small absolute changes are dropped. If change points are dropped this way, this results in a smaller number of segments, which are hence longer. \begin{verbatim} <%=withCapture({ fitP <- pruneByHClust(fit, h=0.25, verbose=-10) })%> \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fitP)[1L], "pruned", "tracks"), aspectRatio=0.35, { plotTracks(fitP) })%>}} \end{center} \caption{Pruned <%=signalType%> segments plotted as in Figure~\ref{figTracks}.} \label{figTracksPruned} \end{figure} \subsection{Report generation} A multipage PDF report that contains both whole-genome and per-chromosome summaries and figures can be generated by: \begin{verbatim} > report(fit, sampleName="CBS", studyName="CBS-Ex", verbose=-10) \end{verbatim} By default, the reports are written to directory \code{reports//} under the current working directory. In addition to the PDF, that directory also contains subdirectory \code{figures/} holding all generated figure files (e.g. PNGs and PDFs) for easy inclusion elsewhere. <%------------------------------------------------------------------- REFERENCES -------------------------------------------------------------------%> \bibliographystyle{natbib} \bibliography{PSCBS} <%------------------------------------------------------------------- APPENDIX -------------------------------------------------------------------%> \clearpage \section*{Appendix} \subsection*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using \code{rfile()} of the R.rsp package. Total processing time after RSP-to-R translation was <%=dt <- round(Sys.time()-t0, digits=2)%> <%=attr(dt, "units")%>. \end{document} PSCBS/vignettes/PSCBS.bib0000644000176200001440000000450614564051545014502 0ustar liggesusers@ARTICLE{OlshenA_etal_2004, author = {Adam B Olshen and E. S. Venkatraman and Robert Lucito and Michael Wigler}, title = {Circular binary segmentation for the analysis of array-based DNA copy number data.}, journal = {Biostatistics}, year = {2004}, volume = {5}, pages = {557--572}, number = {4}, month = {Oct}, doi = {10.1093/biostatistics/kxh008}, keywords = {Breast Neoplasms; Cell Line, Tumor; Computer Simulation; Female; Gene Dosage; Genome, Human; Humans; Olig; e Analysis; onucleotide Array Sequence; CBS}, pii = {5/4/557}, pmid = {15475419}, url = {https://doi.org/10.1093/biostatistics/kxh008} } @ARTICLE{VenkatramanOlshen_2007, author = {E. S. Venkatraman and Adam B Olshen}, title = {{A} faster circular binary segmentation algorithm for the analysis of array {CGH} data.}, journal = {Bioinformatics}, year = {2007}, volume = {23}, pages = {657--663}, number = {6}, month = {Mar}, doi = {10.1093/bioinformatics/btl646}, keywords = {Algorithms; Chromosome Mapping, methods; Gene Dosage, genetics; Oligonucleotide Array Sequence Analysis, methods; Programming Languages; Sequence Alignment, methods; Sequence Analysis, DNA, methods; Software; Time Factors}, pii = {btl646}, pmid = {17234643}, url = {https://doi.org/10.1093/bioinformatics/btl646} } @ARTICLE{OlshenA_etal_2011, author = {Adam B. Olshen and Henrik Bengtsson and Pierre Neuvial and Paul Spellman and Richard A. Olshen and Venkatraman E. Seshan}, title = {Parent-specific copy number in paired tumor-normal studies using circular binary segmentation}, journal = {Bioinformatics}, year = {2011}, volume = {27}, pages = {2038-2046}, number = {15}, doi = {10.1093/bioinformatics/btr329}, pmid = {21666266}, url = {https://doi.org/10.1093/bioinformatics/btl646} } @ARTICLE{BengtssonH_etal_2010, author = {Henrik Bengtsson and Pierre Neuvial and Terence P Speed}, title = {{TumorBoost}: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays}, journal = {BMC Bioinformatics}, year = {2010}, volume = {11}, pages = {245}, number = {1}, month = {May}, doi = {10.1186/1471-2105-11-245}, language = {eng}, medline-pst = {aheadofprint}, pii = {1471-2105-11-245}, pmid = {20462408}, url = {https://dx.doi.org/10.1186/1471-2105-11-245} } PSCBS/NAMESPACE0000644000176200001440000003117315000476755012361 0ustar liggesusers# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # IMPORTS # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - importFrom("R.methodsS3", "setMethodS3") importFrom("R.methodsS3", "getMethodS3") importFrom("R.oo", "setConstructorS3") importFrom("R.utils", "use") ## Importing Object classes importFrom("R.oo", "Package") importFrom("R.utils", "Arguments") importFrom("R.utils", "GenericSummary") ## Importing functions importFrom("R.oo", "extend", "attachLocally", "startupMessage") importFrom("R.cache", "getCachePath", "loadCache", "saveCache") importFrom("R.utils", "cat", "capitalize", "copyDirectory", "createLink", "enter", "enterf", "exit", "filePath", "getAbsolutePath", "getRelativePath", "hpaste", "insert", "isDirectory", "isFile", "isPackageInstalled", "isZero", "less", "loadObject", "more", "popState", "popTemporaryFile", "printf", "pushState", "pushTemporaryFile", "resample", "saveObject", "stext", "subplots", "toCamelCase", "wrap") importFrom("matrixStats", "binMeans", "colCumsums", "colDiffs", "colMins", "colMaxs", "rowAlls", "rowAnys", "rowMins", "weightedMedian") importFrom("graphics", "abline", "arrows", "axis", "box", "lines", "mtext", "par", "plot", "points", "rect", "text") importFrom("grDevices", "col2rgb", "rgb") importFrom("stats", "approx", "cor", "cutree", "density", "end", "mad", "median", "na.omit", "quantile", "sd", "start", "weighted.mean") importFrom("utils", "capture.output", "file_test", "getFromNamespace", "head", "packageVersion", "str", "tail", "write.table", "packageDescription", "install.packages") importFrom("aroma.light", "callNaiveGenotypes", "findPeaksAndValleys", "normalizeTumorBoost") importFrom("DNAcopy", "segments.summary", "smooth.CNA", "CNA", "segment", "getbdry") importFrom("future", "future", "value") importFrom("parallel", "nextRNGStream") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # EXPORTS # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Export all public methods, that is, those without a preceeding dot # in their names. exportPattern("^[^\\.]") # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # S3 methods # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # AbstractCBS S3method("adjustPloidyScale", "AbstractCBS") S3method("all.equal", "AbstractCBS") S3method("as.data.frame", "AbstractCBS") S3method("clearCalls", "AbstractCBS") S3method("drawChangePoints", "AbstractCBS") S3method("drawKnownSegments", "AbstractCBS") S3method("dropChangePoint", "AbstractCBS") S3method("dropChangePoints", "AbstractCBS") S3method("dropRegion", "AbstractCBS") S3method("dropRegions", "AbstractCBS") S3method("extractChromosome", "AbstractCBS") S3method("extractChromosomes", "AbstractCBS") S3method("extractCNs", "AbstractCBS") S3method("extractRegion", "AbstractCBS") S3method("extractRegions", "AbstractCBS") S3method("extractSegment", "AbstractCBS") S3method("extractSegments", "AbstractCBS") S3method("getChangePoints", "AbstractCBS") S3method("getChromosomeOffsets", "AbstractCBS") S3method("getChromosomeRanges", "AbstractCBS") S3method("getChromosomes", "AbstractCBS") S3method("getLocusData", "AbstractCBS") S3method("getLocusSignalNames", "AbstractCBS") S3method("getMeanEstimators", "AbstractCBS") S3method("getSampleName", "AbstractCBS") S3method("getSegments", "AbstractCBS") S3method("getSegmentSizes", "AbstractCBS") S3method("getSegmentTrackPrefixes", "AbstractCBS") S3method("hclustCNs", "AbstractCBS") S3method("mergeThreeSegments", "AbstractCBS") S3method("mergeTwoSegments", "AbstractCBS") S3method("nbrOfChangePoints", "AbstractCBS") S3method("nbrOfChromosomes", "AbstractCBS") S3method("nbrOfLoci", "AbstractCBS") S3method("nbrOfSegments", "AbstractCBS") S3method("normalizeTotalCNs", "AbstractCBS") S3method("normalizeTotalCNs", "PSCBS") S3method("ploidy", "AbstractCBS") S3method("ploidy<-", "AbstractCBS") S3method("plotTracks", "AbstractCBS") S3method("print", "AbstractCBS") S3method("pruneByDP", "AbstractCBS") S3method("pruneByHClust", "AbstractCBS") S3method("renameChromosomes", "AbstractCBS") S3method("report", "AbstractCBS") S3method("resegment", "AbstractCBS") S3method("resetSegments", "AbstractCBS") S3method("sampleCNs", "AbstractCBS") S3method("sampleName", "AbstractCBS") S3method("sampleName<-", "AbstractCBS") S3method("seqOfSegmentsByDP", "AbstractCBS") S3method("setLocusData", "AbstractCBS") S3method("setMeanEstimators", "AbstractCBS") S3method("setPloidy", "AbstractCBS") S3method("setSampleName", "AbstractCBS") S3method("setSegments", "AbstractCBS") S3method("shiftTCN", "AbstractCBS") S3method("tileChromosomes", "AbstractCBS") S3method("updateMeans", "AbstractCBS") S3method("updateMeansTogether", "AbstractCBS") S3method("writeWIG", "AbstractCBS") # CBS S3method("all.equal", "CBS") S3method("as.character", "CBS") S3method("as.data.frame", "CBS") S3method("as.DNAcopy", "CBS") S3method("c", "CBS") S3method("callAmplifications", "CBS") S3method("callArms", "CBS") S3method("callGainsAndLosses", "CBS") S3method("callGLAO", "CBS") S3method("callOutliers", "CBS") S3method("drawCentromeres", "CBS") S3method("drawChromosomes", "CBS") S3method("drawLevels", "CBS") S3method("estimateDeltaCN", "CBS") S3method("estimateStandardDeviation", "CBS") S3method("extractCallsByLocus", "CBS") S3method("extractChromosomes", "CBS") S3method("extractCNs", "CBS") S3method("extractSegmentMeansByLocus", "CBS") S3method("extractSegments", "CBS") S3method("extractTotalCNs", "CBS") S3method("extractWIG", "CBS") S3method("extractWIG", "AbstractCBS") S3method("extractWIG", "PSCBS") S3method("getCallStatistics", "CBS") S3method("getCallStatisticsByArms", "CBS") S3method("getChangePoints", "CBS") S3method("getChromosomeRanges", "CBS") S3method("getFGA", "CBS") S3method("getFGG", "CBS") S3method("getFGL", "CBS") S3method("getFractionOfGenomeAltered", "CBS") S3method("getFractionOfGenomeGained", "CBS") S3method("getFractionOfGenomeLost", "CBS") S3method("getLocusData", "CBS") S3method("getLocusSignalNames", "CBS") S3method("getSegments", "CBS") S3method("getSegmentTrackPrefixes", "CBS") S3method("getSignalType", "CBS") S3method("getSmoothLocusData", "CBS") S3method("highlightArmCalls", "CBS") S3method("highlightCalls", "CBS") S3method("highlightLocusCalls", "CBS") S3method("isSegmentSplitter", "CBS") S3method("isWholeChromosomeGained", "CBS") S3method("isWholeChromosomeLost", "CBS") S3method("joinSegments", "CBS") S3method("mergeNonCalledSegments", "CBS") S3method("mergeTwoSegments", "CBS") S3method("nbrOfAmplifications", "CBS") S3method("nbrOfGains", "CBS") S3method("nbrOfLosses", "CBS") S3method("plot", "CBS") S3method("plotTracks", "CBS") S3method("plotTracksManyChromosomes", "CBS") S3method("pruneBySdUndo", "CBS") S3method("resegment", "CBS") S3method("segmentByCBS", "CBS") S3method("seqOfSegmentsByDP", "CBS") S3method("shiftTCN", "CBS") S3method("signalType", "CBS") S3method("signalType<-", "CBS") S3method("subset", "CBS") S3method("tileChromosomes", "CBS") S3method("updateBoundaries", "CBS") S3method("updateMeans", "CBS") S3method("updateMeansTogether", "CBS") S3method("writeLocusData", "CBS") S3method("writeSegments", "CBS") # CNA S3method("segmentByCBS", "CNA") # data.frame S3method("callSegmentationOutliers", "data.frame") S3method("encodeCalls", "data.frame") S3method("dropSegmentationOutliers", "data.frame") S3method("findLargeGaps", "data.frame") S3method("gapsToSegments", "data.frame") S3method("segmentByCBS", "data.frame") S3method("segmentByNonPairedPSCBS", "data.frame") S3method("segmentByPairedPSCBS", "data.frame") # default S3method("callAllelicBalance", "default") S3method("callSegmentationOutliers", "default") S3method("dropSegmentationOutliers", "default") S3method("exampleData", "default") S3method("findLargeGaps", "default") S3method("findNeutralCopyNumberState", "default") S3method("installDNAcopy", "default") S3method("segmentByCBS", "default") S3method("segmentByNonPairedPSCBS", "default") S3method("segmentByPairedPSCBS", "default") S3method("weightedQuantile", "default") # DNAcopy S3method("as.CBS", "DNAcopy") S3method("drawLevels", "DNAcopy") S3method("estimateStandardDeviation", "DNAcopy") S3method("extractSegmentMeansByLocus", "DNAcopy") S3method("getChromosomes", "DNAcopy") S3method("getSampleNames", "DNAcopy") S3method("nbrOfLoci", "DNAcopy") S3method("nbrOfSamples", "DNAcopy") S3method("nbrOfSegments", "DNAcopy") S3method("writeSegments", "DNAcopy") # matrix S3method("seqOfSegmentsByDP", "matrix") # NonPairedPSCBS S3method("callROH", "NonPairedPSCBS") S3method("getLocusData", "NonPairedPSCBS") S3method("resegment", "NonPairedPSCBS") S3method("updateMeans", "NonPairedPSCBS") # numeric S3method("testROH", "numeric") # PairedPSCBS S3method("adjustPloidyScale", "PairedPSCBS") S3method("applyByRegion", "PairedPSCBS") S3method("arrowsC1C2", "PairedPSCBS") S3method("arrowsDeltaC1C2", "PairedPSCBS") S3method("bootstrapCIs", "PairedPSCBS") S3method("bootstrapSegmentsAndChangepoints", "PairedPSCBS") S3method("bootstrapTCNandDHByRegion", "PairedPSCBS") S3method("calcStatsForCopyNeutralABs", "PairedPSCBS") S3method("callAB", "PairedPSCBS") S3method("callABandHighAI", "PairedPSCBS") S3method("callABandLowC1", "PairedPSCBS") S3method("callAllelicBalanceByDH", "PairedPSCBS") S3method("callCopyNeutral", "PairedPSCBS") S3method("callCopyNeutralByTCNofAB", "PairedPSCBS") S3method("callExtremeAllelicImbalanceByDH", "PairedPSCBS") S3method("callGainNeutralLoss", "PairedPSCBS") S3method("callGNL", "PairedPSCBS") S3method("callGNLByTCNofAB", "PairedPSCBS") S3method("callGNLByTCNofABv1", "PairedPSCBS") S3method("callLOH", "PairedPSCBS") S3method("callLowC1ByC1", "PairedPSCBS") S3method("callNTCN", "PairedPSCBS") S3method("callROH", "PairedPSCBS") S3method("callROHOneSegment", "PairedPSCBS") S3method("clearBootstrapSummaries", "PairedPSCBS") S3method("drawChangePointsC1C2", "PairedPSCBS") S3method("drawConfidenceBands", "PairedPSCBS") S3method("drawLevels", "PairedPSCBS") S3method("estimateDeltaAB", "PairedPSCBS") S3method("estimateDeltaABBySmallDH", "PairedPSCBS") S3method("estimateDeltaCN", "PairedPSCBS") S3method("estimateDeltaLOH", "PairedPSCBS") S3method("estimateDeltaLOHByMinC1ForNonAB", "PairedPSCBS") S3method("estimateHighDHQuantileAtAB", "PairedPSCBS") S3method("estimateKappa", "PairedPSCBS") S3method("estimateKappaByC1Density", "PairedPSCBS") S3method("estimateMeanForDH", "PairedPSCBS") S3method("estimateStdDevForHeterozygousBAF", "PairedPSCBS") S3method("extractC1C2", "PairedPSCBS") S3method("extractCallsByLocus", "PairedPSCBS") S3method("extractCNs", "PairedPSCBS") S3method("extractDeltaC1C2", "PairedPSCBS") S3method("extractDhSegment", "PairedPSCBS") S3method("extractLocusLevelC1C2", "PairedPSCBS") S3method("extractLocusLevelTCN", "PairedPSCBS") S3method("extractMinorMajorCNs", "PairedPSCBS") S3method("extractSegmentDataByLocus", "PairedPSCBS") S3method("extractSegments", "PairedPSCBS") S3method("extractTCNAndDHs", "PairedPSCBS") S3method("findBootstrapSummaries", "PairedPSCBS") S3method("getBootstrapLocusSets", "PairedPSCBS") S3method("getChromosomeOffsets", "PairedPSCBS") S3method("getChromosomeRanges", "PairedPSCBS") S3method("getLocusData", "PairedPSCBS") S3method("hasBootstrapSummaries", "PairedPSCBS") S3method("linesC1C2", "PairedPSCBS") S3method("linesDeltaC1C2", "PairedPSCBS") S3method("mergeTwoSegments", "PairedPSCBS") S3method("plot", "PairedPSCBS") S3method("plotC1C2", "PairedPSCBS") S3method("plotDeltaC1C2", "PairedPSCBS") S3method("plotTracks", "PairedPSCBS") S3method("plotTracks1", "PairedPSCBS") S3method("plotTracks2", "PairedPSCBS") S3method("plotTracksManyChromosomes", "PairedPSCBS") S3method("pointsC1C2", "PairedPSCBS") S3method("pointsDeltaC1C2", "PairedPSCBS") S3method("postsegmentTCN", "PairedPSCBS") S3method("resegment", "PairedPSCBS") S3method("segmentByNonPairedPSCBS", "PairedPSCBS") S3method("segmentByPairedPSCBS", "PairedPSCBS") S3method("seqOfSegmentsByDP", "PairedPSCBS") S3method("shiftTCN", "PairedPSCBS") S3method("tileChromosomes", "PairedPSCBS") S3method("unTumorBoost", "PairedPSCBS") S3method("updateMeans", "PairedPSCBS") S3method("updateMeansC1C2", "PairedPSCBS") S3method("updateMeansTogether", "PairedPSCBS") # PSCBS S3method("as.data.frame", "PSCBS") S3method("c", "PSCBS") S3method("drawChangePoints", "PSCBS") S3method("extractChromosomes", "PSCBS") S3method("getChangePoints", "PSCBS") S3method("getLocusData", "PSCBS") S3method("getLocusSignalNames", "PSCBS") S3method("getSegments", "PSCBS") S3method("getSegmentTrackPrefixes", "PSCBS") S3method("isLocallyPhased", "PSCBS") S3method("isSegmentSplitter", "PSCBS") S3method("writeSegments", "PSCBS") PSCBS/NEWS.md0000644000176200001440000023537315000515154012233 0ustar liggesusers# Version 0.68.0 [2025-04-18] ## Documentation * Fix minor help-page issues. ## Bug Fixes * `segmentByCBS()` had an internal bug which triggered an error on `could not find function "nbrOfSegments"`, which began with **future** 1.40.0. # Version 0.67.0 [2024-02-16] ## Documentation * Fix minor help-page issues. ## Miscellaneous * Package no longer suggests the **Hmisc** package, because it's actually not used. See NEWS entry for v0.66.0 for details. ## Deprecated and Defunct * Removed defunct `append()` for `AbtractCBS`. * Removed defunct `load()` and `save()` for `AbtractCBS`. * After removing the above functions, `library(PSCBS)` no longer reports on functions being masked. # Version 0.66.0 [2021-10-22] ## Significant Changes * Package no longer require the **Hmisc** package, which was used for its `wtd.quantile()` function. Instead, we have adopted its GPL (>=2) code. The reason for doing so is that **Hmisc** no longer installs out of the box on platforms, e.g. macOS M1, but also that **Hmisc** has a large number of package dependencies, which adds an unnecessary installation weight to the **PSCBS** package for this single function. ## Code Refactoring * Update package tests to test with 'multisession' futures. ## Bug Fixes * `segmentByCBS()` and `segmentByPairedPSCBS()` would produce warnings on possibly unreliable random numbers due to parallel processing in the case they segmented multiple chromosomes or segments. * Fixed a few partial `getSegments()` argument name matching (`splitter` -> `splitters`). ## Deprecated and Defunct * `append(x, y)` for `CBS` and `PSCBS` objects, deprecated since v0.64.0 is defunct; use `c(x, y)` instead. * `save()` for `CBS` and `PSCBS` objects and corresponding `CBS$load()` and `PSCBS$load()` methods are defunct. We recommend to use base-R functions `saveRDS()` and `readRDS()` instead. If backward compatibility with the defunct `save()` and `load()` methods, the `saveObject()` and `loadObject()` functions from the **R.utils** package can be used. # Version 0.65.0 [2019-05-04] ## New Features * The PDF report produced by `report()` for Paired PSCBS results will now provide an estimate of normal contamination together with a disclaimer. ## Bug Fixes * A sanity check in `segmentByPairedPSCBS()` could produce an error on `'length(x) = 5 > 1' in coercion to 'logical(1)'` when running with `_R_CHECK_LENGTH_1_LOGIC2_=true`. This bug did _not_ affect the results of PSCBS. * Report templates used by `report()` would produce error `Error in unit(x, default.units) : 'x' and 'units' must have length > 0` if there are too few loci to plot. This would typically happen when reporting on human chromosome 25 results. ## Deprecated and Defunct * Argument `preserveScale` of `segmentByPairedPSCBS()` is now defunct. # Version 0.64.0 [2018-08-12] ## New Features * Added `c()` for `CBS` and `PSCBS` objects. ## Performance * `segmentByCBS()` no longer performs garbage collection, which happened indirectly via a `system.time()` call that does GC by default. ## Bug Fixes * `plotTrack()` for `CBS` objects would produce error `Argument 'Clim' is not a vector: NULL` when the signal type was unknown. Now it will assume (non-logged) copy-number ratios so it can choose a default `Clim` range. ## Deprecated and Defunct * Removed `bootstrapDHByRegion()`, which was defunct since 0.44.0 (Feb 2015). * `append(x, y)` for `CBS` and `PSCBS` objects is deprecated; use `c(x, y)` instead. * Use of argument `preserveScale` for `segmentByPairedPSCBS()` is now deprecated and ignored. it's value is now fixed to FALSE, which has been the default since **PSCBS** 0.50.0 (Oct 2015). # Version 0.63.0 [2017-06-27] ## Significant Changes * Package now depends on R (>= 3.2.0) and Bioconductor (>= 3.1) packages. ## New Features * `estimateDeltaCN()` for `PairedPSCBS` gained argument `flavor` and new estimator `flavor = "delta(mode)"`. * Added `isLocallyPhased()` for `PSCBS`. ## Code Refactoring * Now package imports **aroma.light** instead of only suggesting it. * Package tests no longer test against the deprecated 'lazy' strategy of **future**. # Version 0.62.0 [2016-11-10] ## New Features * Added `normalizeTotalCNs()` for `PSCBS` objects. * REPORTS: Updated report template for `PairedPSCBS` object such that reports are also generated from DH-only data, i.e. when there are no BAF signals (which may happen with DNA-Seq data). * Added `splitters = TRUE` as the default for `setSegments()`. ## Code Refactoring * CLEANUP: Minor internal cleanup and restructuring. # Version 0.61.0 [2016-02-03] ## Significant Changes * Package now requires R (>= 3.1.2) released October 2014, because of its dependency on the **listenv** package. ## New Features * `segmentByPairedPSCBS()` gained argument `rho` for paired PSCBS segmentation on total CNs (TCNs) and decrease-of-heterozygosity signals (DHs) as an alternative to for instance TCN and allele B fractions (BAFs). ## Bug Fixes * Segmentation using futures where not fully reproducible when known segments where specified. Fixed by changing how the random number stream is set and used. # Version 0.60.0 [2015-11-17] ## New Features * PARALLEL: Add support for parallel processing via futures by utilizing the **future** package. Parallel segmentation over multiple chromosomes (or known segments) done by `segmentByCBS()` and `segmentByPairedPSCBS()` is enabled by `future::plan("multicore")`. * REPRODUCIBILITY: Whenever argument `seed` is given, the L'Ecuyer-CMRG stream is now used to generate random numbers. For backward compatibility with other types of random number generators, don't specify argument `seed` but instead use `set.seed()` to set the seed before calling the method. ## Code Refactoring * Bump package dependencies. # Version 0.50.0 [2015-10-14] ## Significant Changes * Now argument `preserveScale` for `segmentByPairedPSCBS()` defaults to FALSE. In the past the default has effectively been TRUE, but has given a warning since v0.43.0 (June 2014) that it eventually will be changed to FALSE. Now it will give a warning that it has changed, unless the option is explicitly specified. This new warning will eventually be removed in a future version. # Version 0.45.1 [2015-09-16] ## New Features * More informative error messages when `append()` for `CBS` or `PSCBS` fail. ## Bug Fixes * `segmentByCBS(, ..., w, knownSegments)` would give internal assertion errors if one of the priorly known segments would have zero data points. Thanks to Kirill Tsukanov (Moscow) and Eric Talevich (UCSF) for reporting on this. # Version 0.45.0 [2015-09-11] ## Significant Changes * Package now requires R (>= 3.1.1) released July 2014. This allows us to use Bioconductor (>= 3.0) (October 2014). ## New Features * `segmentByCBS()` gained argument `avg`. * Add `writeWIG()` for `CBS` objects. * `pruneByHClust()` no longer gives a message about method `"ward"` is now named `"ward.D"`. * Added `skip = TRUE` to `report()`. ## Bug Fixes * `plotTracks()` for `CBS` ignored arguments `cex`, `col` and `meanCol` if two or more chromosomes were plotted. * `joinSegments()`, `resetSegments()`, and `pruneBySdUndo()` gave errors for multi- chromosome (>= 2) segmentation results. * `segmentByCBS()` would ignore argument `w` (weights) if more than one chromosome was fitted. * `tileChromosomes()` for `CBS` returned incorrect locus data. * `gapsToSegments(gaps)` gave an error if `nrow(gaps) == 0`, or it contained no `chromosome` column. * `findLargeGaps()` could return NULL. Now it always returns a data.frame. * The `report()` RSP-embedded TeX templates for `CBS` and `PairedPSCBS` data did not escape sample and data set names to LaTeX in all places needed. ## Code Refactoring * ROBUSTNESS: Package test coverage is 62%. * ROBUSTNESS: Explicitly importing core R functions. # Version 0.44.0 [2015-02-22] * Package now requires R (>= 3.0.3) and Bioconductor (>= 2.13), which are from March 2014 and are in fact old. it's recommended to use a more recent R version. ## Deprecated and Defunct * CLEANUP: `bootstrapDHByRegion()` is defunct (was deprecated since 2013). ## Code Refactoring * ROBUSTNESS: Package test coverage is 58%. * ROBUSTNESS: Forgot to declare some S3 methods in NAMESPACE. * SPEEDUP: Now using more functions of **matrixStats**. # Version 0.43.0 [2014-06-08] ## Significant Changes * Now `segmentByPairedPSCBS()` gives a warning about future change of the default value of argument `preserveScale` (from current TRUE to FALSE). The warning only appears if the argument is not specified explicitly. * Package now requires R (>= 3.0.0) and Bioconductor (>= 2.13), which were released April 2013 and are in fact old and it's recommended to use a more recent version of R. ## Code Refactoring * Now using `use()` of **R.utils** where possible. * Bumped package dependencies. # Version 0.42.2 [2014-05-24] ## Code Refactoring * Bumped package dependencies. # Version 0.42.1 [2014-05-05] ## Bug Fixes * `pruneByHClust()` for `PairedPSCBS` would give an error on `unable to find an inherited method for function 'anyMissing' for signature '"PairedPSCNSegments"'`, unless the object contained bootstrap statistics. This is no longer needed. Thanks to Junsong Zhao, Los Angeles, CA for reporting on this. # Version 0.42.0 [2014-04-25] ## Code Refactoring * Minor speedup (a few percents) by now byte compiling the package by default. * CLEANUP: Dropped unnecessary usage of `::`. * Bumped package dependencies. # Version 0.41.4 [2014-03-30] ## New Features * GENERALIZATION: Now `callROH()` also works if paired PSCBS was done with only `muN` available (and not `betaN`). In that case, it assumes that all genotype confidence scores are equal. * Updated the ordering and the defaults of `testROH()` arguments to make it clear that `betaN` is optional and only used if `csN` is not given. * As an alternative to argument `CT`, `segmentByPairedPSCBS()` now accepts arguments `thetaT` and `thetaN`, in case `CT` is calculated as `CT = 2 * thetaT / thetaN`. # Version 0.41.3 [2014-03-29] ## New Features * Methods no longer generates warnings on `in max(c(NA_integer_, NA_integer_), na.rm = TRUE) : no non-missing arguments to max; returning -Inf`. ## Bug Fixes * In rare cases, `callROH()` could throw `Error in if (is.na(delta)) { : argument is of length zero`. # Version 0.41.2 [2014-03-28] ## New Features * Added argument `preserveScale` to `segmentByPairedPSCBS()`, which is passed as is to `normalizeTumorBoost()` with the default being TRUE corresponding to the previous default behavior. # Version 0.41.1 [2014-03-28] ## New Features * Added `unTumorBoost()` to recalculating the segment means and other statistics for a given `PairedPSCBS` profile based on non-TumorBoosted tumor BAFs (rather than TumorBoost:ed tumor BAFs). # Version 0.41.0 [2014-03-26] ## New Features * Now `estimateKappaByC1Density()` give more informative error messages if it failed to identify modes for estimating the parameter. * Added argument `from` to `estimateKappaByC1Density()`. ## Bug Fixes * `updateMeansC1C2()` for `PairedPSCBS` did not handle missing values (= "splitters") in the `c1c2Swap` field. * `updateMeans()` for `PairedPSCBS` and `NonPairedPSCBS` returned the incorrect DH segment levels for region in AB if `adjustFor = "ab"` and likewise for segments in LOH if `adjustFor = "loh"`. This bug does *not* affect any of **PSCBS** methods themselves, because none of them utilize those `adjustFor` options. ## Code Refactoring * Bumped package dependencies. # Version 0.40.4 [2014-02-04] ## Bug Fixes * `all.equal()` for `CBS` would pass the first/dispatch argument to `NextMethod()` as `target = target` and not as `object = target`, which would result in it being passed it twice both named and non-named where the latter would become argument `tolerance = target` in an internal call to `all.equal()` for numerics. In recent R-devel version this would generate `Error in all.equal.numeric(target[[i]], current[[i]], check.attributes = check.attributes, : 'tolerance' should be numeric Calls: stopifnot ... all.equal.default -> all.equal.list -> all.equal -> all.equal.numeric`. # Version 0.40.3 [2014-01-29] ## New Features * ROBUSTNESS: Now `segmentByPairedPSCBS()` asserts that argument `muN` is not all NAs. Similarily, if `muN` is called from `betaN` the same assertion is done after calling. # Version 0.40.2 [2013-12-17] ## New Features * Now `estimateDeltaCN()` for `CBS` have the option to estimate the size of a copy-number unit based on the change-point magnitutes, in addition to the estimator based on the density of segment means. ## Bug Fixes * `getChangePoints()` for `CBS` returned empty results. # Version 0.40.1 [2013-12-09] ## Documentation * The CBS vignette referred to C1 and C2 in one of the code examples. ## Code Refactoring * Bumped package dependencies. # Version 0.40.0 [2013-12-07] ## Code Refactoring * CLEANUP: No longer a need for an ad-hoc NAMESPACE import. # Version 0.39.8 [2013-12-04] ## Documentation * Now the vignette sections on dropping outliers before segmentation explains why outliers are dropped whereas in the original CBS publication they were shrunk ("smoothed"). Also, added help for `dropSegmentationOutliers()`. # Version 0.39.7 [2013-11-27] ## New Features * Added `callGLAO()` for `CBS`. * Added `encodeCalls()` for `data.frame` object returned by `getLocusData(..., addCalls = TRUE)`. ## Code Refactoring * Bumped package dependencies. # Version 0.39.6 [2013-11-23] ## New Features * Added `clearCalls()` for `AbstractCBS`. * Added `extractSegmentDataByLocus()` for `PairedPSCBS`. ## Bug Fixes * `estimateDeltaCN()` for `CBS` assumed **aroma.light** was attached. # Version 0.39.5 [2013-11-15] ## New Features * Added `estimateDeltaCN()` for `CBS`. Added package system test. # Version 0.39.4 [2013-11-14] ## Bug Fixes * `callGainsAndLosses()` for `CBS` would not estimate the median median CN level correctly if there were "empty" segments (e.g. gaps). This was/is due to a bug in `segments.summary()` of the **DNAcopy** package. Instead, we are now calculating the segment median levels ourselves. Added a system package test for `callGainsAndLosses()`. # Version 0.39.3 [2013-11-05] ## New Features * Added basic implementations of `setLocusData()` and `setSegments()` for `AbstractCBS`. # Version 0.39.2 [2013-10-28] ## New Features * Now `plotTracksManyChromosomes()` for `PairedPSCBS` also supports tracks `"c1,c2"`, `"c1"`, and `"c2"`. # Version 0.39.1 [2013-10-25] ## New Features * Now `plotTracksManyChromosomes()` uses the locus data field `rho` when plotting DH locus-level data. It only recalculates it from the tumor BAFs if the DH signals are not available - if so a warning is generated. ## Bug Fixes * The `rho` signals returned by `getLocusData(..., fields = "full")` for `PairedPSCBS` would have values also for homozygote SNPs. # Version 0.39.0 [2013-10-23] ## New Features * Now all warnings generated by `DNAcopy::CNA()` are suppressed, including the common one on `array has repeated maploc positions`. * Added `getBootstrapLocusSets()` for `PairedPSCBS`. Added a package system test for it. * Added argument `subset` to `applyByRegion()` for `PairedPSCBS`. * Added `clearBootstrapSummaries()` for `PairedPSCBS`. * SPEEDUP: Added argument `cache` to `bootstrapSegmentsAndChangepoints()`, which caches the results to file if `cache = TRUE`. # Version 0.38.6 [2013-10-20] ## Bug Fixes * `plotTracks()` for `PairedPSCBS` would use argument `Clim` for `Blim` as well, regardless of what argument `Blim` is. This bug was introduced in v0.38.3. ## Code Refactoring * Internal restructuring on how bootstrapping of segment means is done. # Version 0.38.5 [2013-10-18] ## Bug Fixes * The CBS and Paired PSCBS report templates assumed that the **R.utils** package is attached. # Version 0.38.4 [2013-10-15] ## Code Refactoring * CLEANUP: Removed a few unnecessary NAMESPACE imports. * Bumped package dependencies. # Version 0.38.3 [2013-10-14] ## New Features * Now `plotTracks()` for `CBS` and `PSCBS` gives a more informative error if `Clim` or `Blim` is invalid. If using `"auto"` (only for `CBS`) and the limits could not be inferred due to an unknown or unset signal type, an informative error message reports on this as well. ## Code Refactoring * Now the package vignettes are in `vignettes/`, and not in `inst/doc/`, which will not be supported by R (>= 3.1.0). * ROBUSTNESS: The overriding of `append()` to become a generic function does now call `base::append()` in the default, instead of copy the latter. All this will eventually be removed, when proper support for `c`, `[`, `[[` etc. has been added everywhere. * CLEANUP: Now explicitly importing only what is needed in NAMESPACE. # Version 0.38.2 [2013-10-13] ## Bug Fixes * While attaching the package, it could cause a cyclic loading of namespaces. # Version 0.38.1 [2013-10-08] ## New Features * Now `getSmoothLocusData()` for `CBS` also returns column `count` which specifies the number of (finite) loci averaged over in each bin. ## Documentation * Vignette 'Total copy-number segmentation using CBS' would display the same plot as vignette 'Parent-specific copy-number segmentation using Paired PSCBS'. * Renamed vignette 'Paired PSCBS' to 'Parent-specific copy-number segmentation using Paired PSCBS'. ## Bug Fixes * `tileChromosomes()` for `CBS` did not set the `tiledChromosomes` attribute due to a typo. This caused `plotTracks()` for `CBS` to horizontally misplace the plotted segment levels. Added a system tests for this for `CBS` and `PairedPSCBS` objects. Thanks to Ilari Scheinin at VUMC for reporting on this. ## Code Refactoring * Bumped package dependencies. # Version 0.38.0 [2013-09-27] ## Code Refactoring * SPEEDUP: `R CMD check` is now significantly faster due to copying of pre-generated calculations ("memoization"). For instance, the the same segmentation tests are roughly 40% faster compared to version 0.37.2. * Now **PSCBS** imports **R.cache** (used to only suggest it). # Version 0.37.2 [2013-09-27] ## Code Refactoring * SPEEDUP: Now utilizing **matrixStats** functions in more places. * ROBUSTNESS: Further improved how **aroma.light** is handled for backward compatibility. * Bumped package dependencies. # Version 0.37.1 [2013-09-26] ## Code Refactoring * CLEANUP: Now package avoids attaching suggested packages such as **R.cache**, **aroma.light**, and **Hmisc** by only importing the set of functions needed via `::`. This way those packages are only loaded. Packages that still need to be attached are done so "quietly". * CLEANUP: Minor adjustments to some of the internal workarounds for older versions of **matrixStats** and **aroma.light**. ## Bug Fixes * Forgot to import several functions from **matrixStats**. These went undetected because **aroma.light** (<= 1.31.5) attaches the **matrixStats**. * `segmentByPairedPSCBS()` assumed **aroma.light** was attached. * One of the system tests assumed **R.utils** was attached. # Version 0.37.0 [2013-09-21] ## Bug Fixes * WORKAROUND: For now, package attaches the **utils** package. This is needed due to what appears to be a bug in how **R.oo** finalizes Object:s assuming **utils** is attached, which may not be the case (unless **R.oo** itself is attached). * `callGNL()` for `PairedPSCBS` used non-defined `verbose` object. ## Code Refactoring * CLEANUP: Package no longer attaches **R.utils**, only imports it. * ROBUSTNESS: Now package imports only what is needed from **DNAcopy**. # Version 0.36.2 [2013-09-18] ## Documentation * Added vignette 'Total copy-number segmentation using CBS'. * WORKAROUND: For R (< 3.0.0), `hclustCNs()` for `AbstractCBS` would generate `Error in rowAlls(ok) : could not find function "loadMethod"`. This seems to be a bug in R (< 3.0.0), which we can avoid by attaching the **methods** package in `hclustCNs()`. ## Code Refactoring * ROBUSTNESS: Now package imports **matrixStats** (previously suggested). * ROBUSTNESS: Now package declares S3 methods in the NAMESPACE. * ROBUSTNESS: Package vignettes no longer assumes that the **R.rsp** package is attached. * ROBUSTNESS: Forgot to import `R.methodsS3::appendVarArgs()`. * Bumped package dependencies. # Version 0.36.1 [2013-09-10] ## Code Refactoring * CLEANUP: Package no longer utilizes `:::`. # Version 0.36.0 [2013-08-15] ## New Features * Made `extractMinorMajorCNs()` for `PairedPSCBS` acknowledge additional fields related to (C1,C2). # Version 0.35.6 [2013-08-01] ## Code Refactoring * Updated the vignettes to utilize the new **R.rsp** features. # Version 0.35.5 [2013-07-19] ## New Features * ROBUSTNESS: Added a sanity check on the estimates of (tauA, tauB) when they are estimated from data in `segmentByNonPairedPSCBS()`. # Version 0.35.4 [2013-07-11] ## Code Refactoring * Updated the `Makefile` for the vignettes and added `.Rinstignore` such that auxiliary (bib and bst) LaTeX files are not installed but part of the build so they are available to `R CMD check`, which is recently needed by R devel. * Bumped package dependencies. # Version 0.35.3 [2013-05-25] ## Code Refactoring * Minor speedup by replacing all `rm(x)` with `x <- NULL`, cf. R-devel thread 'Assigning NULL to large variables is much faster than rm() - any reason why I should still use rm()?' on May 25, 2013. # Version 0.35.2 [2013-05-20] ## Documentation * CRAN POLICY: Now all Rd `\usage{}` lines are at most 90 characters long. # Version 0.35.1 [2013-05-07] ## New Features * Now `estimateDeltaCN()` for `PairedPSCBS` adjust for the ploidy, if set. * Added `ploidy()` and `ploidy()<-` for `AbstractCBS`. * Now `tileChromosomes()` no longer gives warnings on `max(i): no non-missing arguments to max; returning -Inf`. # Version 0.35.0 [2013-04-23] ## New Features * SPEEDUP: Now `bootstrapTCNandDHByRegion()` for `PairedPSCBS` always estimates the default quantiles in addition to any requested ones. * SPEEDUP: Made `bootstrapTCNandDHByRegion()` much faster by adding `use.names = FALSE` to two internal `unlist()` statements. ## Bug Fixes * `updateMeans()` for `PairedPSCBS` and `NonPairedPSCBS` could include a signal from a neighboring segment when averaging, iff that signal was located at the exact locus of the change point. Thanks Ingrid Lonnstedt (WEHI) for reporting on this. # Version 0.34.9 [2013-04-22] ## Bug Fixes * `updateMeans()` would not always preserve the originally specified segment-mean level estimator, if different from a (sample) mean estimator, e.g. `avgDH = "median"`. This could result in for instance `callAB()` failing on internal sanity checks. * Segment levels drawn by `plotTracks()` would have incorrect genomic locations for chromosome 2 and beyond. This bug was introduced in v0.34.7. ## Code Refactoring * Utilizing new `startupMessage()` of **R.oo**. # Version 0.34.8 [2013-04-20] ## Deprecated and Defunct * Removed previously deprecated methods for `AbstractCBS`. # Version 0.34.7 [2013-04-18] ## New Features * Added more arguments to `plotTracks()`. * Now `drawLevels()` and `drawConfidenceBands()` for `CBS` and `PairedPSCBS` also works for multiple chromosomes. ## Bug Fixes * One of the system tests for `segmentByPairedPSCBS()` failed in the case when the data was downsampled (in order to meet the CRAN requirements). The workaround is to use a fix `deltaAB` parameter in that case. * Internal `calcStatsForCopyNeutralABs()` would give an error if there was exactly two AB segments. # Version 0.34.6 [2013-04-11] ## Bug Fixes * `plotTracks(fit, callLoci = TRUE)` would color loci incorrectly if more than one chromosome are plotted. # Version 0.34.5 [2013-04-09] ## New Features * Now `callROH()` gives an informative error if called on a `NonPairedPSCBS` object. # Version 0.34.4 [2013-04-05] ## New Features * Added more end-user control to `plotTracks()`. # Version 0.34.3 [2013-04-04] ## Code Refactoring * Now package builds with both **R.rsp** (< 0.9.1) and **R.rsp** (>= 0.9.1). # Version 0.34.2 [2013-03-28] ## New Features * Now `callGainNeutralLoss()`, utilizes `callCopyNeutral()` by default. # Version 0.34.1 [2013-03-21] ## New Features * Updated the report generator and its RSP templates. ## Documentation * Clarified in the **PSCBS** vignette that the NTCN caller is under development, experimental. ## Code Refactoring * SPEEDUP: Made `dropChangePoints()` faster by only updating the segment statistics/means at the very end. # Version 0.34.0 [2013-03-19] ## New Features * CALLING: Defined a formal hypothesis test for how segments are called copy- neutral in TCN (NTCN), with the null hypothesis being that a segment is NTCN. In order for a segment to not be NTCN, its confidence interval has to be completely outside the null region. This changed how `callCopyNeutralByTCNofAB()` for `PairedPSCBS` calls segments; it is now a bit more conservative in rejecting NTCN. # Version 0.33.4 [2013-03-19] ## New Features * ROBUSTNESS: Now `calcStatsForCopyNeutralABs()` for `PairedPSCBS` does a better job in identifying the TCN mode of the AB segments. * Added argument `flavor` to `findNeutralCopyNumberState()` specifying how to identify the main mode of the AB segments. * VISUALIZATION: Now `plotTracks()` for `PairedPSCBS` displays thresholds for calling AB, LOH and and NTCN. # Version 0.33.3 [2013-03-12] ## Documentation * Documented `tauA` and `tauB` in the help for `segmentByNonPairedPSCBS()`. # Version 0.33.2 [2013-03-09] ## New Features * Added `getLocusData()` for `PairedPSCBS` and `NonPairedPSCBS`. ## Documentation * Updated the vignettes and the report templates to utilize the new **ggplot2** themes - **ggplot2** no longer gives a warning on using deprecated functions. * Now `report()` for `AbstractCBS` also includes files listed in the optional file `.install_extras` of the source RSP template directory. The same filename is used by `R CMD build/check` for including additional source files needed to build the vignettes. ## Code Refactoring * Added an `Authors@R` field to the DESCRIPTION. # Version 0.33.1 [2013-03-07] ## Documentation * Preparing package vignettes for the upcoming R 3.0.0 support for non-Sweave vignettes. ## Software Quality * Relaxed the internal precision tests of `testROH()`. This was done in response to the CRAN farm lowering its precision on some hosts. # Version 0.33.0 [2013-03-05] ## New Features * Added argument `typeOfWeights` to `estimateKappaByC1Density()` for `PairedPSCBS`, and hence indirectly to `estimateKappa()`. The default is `typeOfWeights = "dhNbrOfLoci"`, which may give too much overall weight to very long segments causing the estimator to fail when there are only a few number of "C1 = 0" segments. An alternative is to use `typeOfWeights = "sqrt(dhNbrOfLoci)"`. # Version 0.32.6 [2013-03-04] ## Documentation * Updated the help usage section for all static methods. # Version 0.32.5 [2013-02-09] ## Bug Fixes * `bootstrapTCNandDHByRegion()` for `PairedPSCBS` did not bootstrap from all available loci when calculating total CNs statistics, iff the segment had been called run-of-homozygosity (ROH). Internal validation tests caught this. Thanks to Oscar Rueda at the Cancer Research UK Cambridge Institute for reporting on this. ## Code Refactoring * Added a `VignetteBuilder` field to DESCRIPTION. # Version 0.32.4 [2013-02-07] ## New Features * Improved some verbose outputs of `bootstrapTCNandDHByRegion()`. # Version 0.32.3 [2013-02-05] ## New Features * Now `pruneByHClust()` drops any existing segment calls and quantile mean-level estimates. # Version 0.32.2 [2013-02-01] ## New Features * Added `resetSegments()` for `AbstractCBS`, which drops extra segments columns (e.g. bootstrap statistics and calls) except those obtained from the segment algorithm. ## Documentation * Added a paragraph on `avgDH = "median"` to the **PSCBS** vignette's 'Experimental' section. ## Code Refactoring * ROBUSTNESS: Now **aroma.light** is explicitly required in cases where it is needed. # Version 0.32.1 [2013-02-01] ## Bug Fixes * `segmentByPairedPSCBS(..., avgDH = "median")` only worked for single- chromosome data. Same for `avgTCN = "median"`. Thanks Ritu Roy at UCSF for reporting on this. # Version 0.32.0 [2013-01-16] ## New Features * Added arguments `avgTCN` and `avgDH` to `segmentByPairedPSCBS()`. * Now `updateMeans()` and `updateMeansTogether()` methods can estimate the mean levels either by the sample mean or the median. # Version 0.31.0 [2013-01-05] ## Code Refactoring * CLEANUP: Now packages **R.methodsS3** and **R.oo** are only imported. * CLEANUP: Package no longer explicitly imports **digest**. # Version 0.30.0 [2012-11-05] ## New Features * GENERALIZATION: Now `bootstrapTCNandDHByRegion()` works for more "flavors", e.g the default (`"tcn"`) used by `segmentByNonPairedPSCBS()`. # Version 0.29.9 [2012-11-05] ## Documentation * FIX: `example(segmentByNonPairedPSCBS)` was for the paired case. ## Code Refactoring * CRAN POLICY: Further speed up of examples such that they run faster with `R CMD check`. # Version 0.29.8 [2012-11-04] ## Code Refactoring * CLEANUP: Replaced all `whichVector()` with `which()`, because the latter is now the fastest again. # Version 0.29.7 [2012-11-03] ## Code Refactoring * Updated deprecated **ggplot2** functions in the RSP reports. # Version 0.29.6 [2012-11-01] ## Code Refactoring * Bumped package dependencies. * CRAN POLICY: Made the examples run faster for `R CMD check`. # Version 0.29.5 [2012-10-16] ## Bug Fixes * ROBUSTNESS: No longer passing `...` to `NextMethod()`, cf. R-devel thread "Do *not* pass '...' to NextMethod() - it'll do it for you; missing documentation, a bug or just me?" on Oct 16, 2012. # Version 0.29.4 [2012-09-23] ## New Features * Now `plotTracks()` [and `plotTracksManyChromosomes()`] draws segment levels such that it is easier to see them even when they are overlapping. # Version 0.29.3 [2012-09-21] ## New Features * SPEEDUP: By default `bootstrapTCNandDHByRegion()` for `PairedPSCBS` no longer do sanity checks within the bootstrap loop. This significantly speed up the method. To run checks, use argument `.debug = TRUE`. In addition, the `callNnn()` methods that need to call this method, does it by decreasing the amount of verbose output substantially, which in turn speeds up the process a fair bit. * Now `getSegments(..., splitters = TRUE)` for `CBS` and `PSCBS` inserts NA rows wherever there is a "gap" between segments. A "gap" is when two segments are not connected (zero distance). * ROBUSTNESS: Now `append()` for `CBS` and `PSCBS` drops column `length` from `knownSegments`, iff it exists. * Now `nbrOfChangePoints()` for `AbstractCBS` calculates only change points of connected neighboring segments. ## Bug Fixes * `seqOfSegmentsByDP()` for `AbstractCBS` would not handle empty segments, which could occur if `knownSegments` for instance included centromere gaps. * `segmentByCBS(... knownSegments)` could return segments for chromosome 0 even though it did not exist in the input data. # Version 0.29.2 [2012-09-18] ## New Features * REPORT: Now `report()` for `AbstractCBS` looks for the RSP template in `templates/`, and as a backup in `templates,PSCBS/`. If the latter does not exist, it is automatically created as a soft link to `templates/` of the **PSCBS** package. This allows anyone to create their own customized copy (in `templates/`) of the default **PSCBS** RSP report. * REPORT: Now `report(fit, ..., rspTags)` for `AbstractCBS` looks for the RSP template named `(,),report.tex.rsp`, where `` is `class(fit)[1]` and argument `rspTags` is an optional comma-separated character string/vector. This makes it possible to have different types of report for the same class of objects. * REPORT: Added argument `force` to `report()` for `AbstractCBS`. This will copy the RSP template files again, although they are already in `reports/` output directory. # Version 0.29.1 [2012-09-15] ## New Features * Added argument `dropMissingCT` to `segmentByPairedPSCBS()`. # Version 0.29.0 [2012-09-14] ## New Features * Added trial version of `pruneByDP()` for `AbstractCBS`. # Version 0.28.6 [2012-09-13] ## New Features * Now `tileChromosomes()` also adjusts `knownSegments`. * Added argument `dropGaps` to `gapsToSegments()`. * Updated `all.equal()` for `AbstractCBS` to compare locus-level data, segments, and other fields. # Version 0.28.5 [2012-09-13] ## New Features * SPEEDUP: Now `segmentByCBS(..., undo = +Inf)` returns much faster, which is possible because there is no need to identify new change points. # Version 0.28.4 [2012-09-13] ## New Features * CONSISTENCY FIX: Changed the behavior of extreme values of argument `undo` to `segmentByCBS()` such that `undo = 0` (was `undo = +Inf`) now means that it will not ask `DNAcopy::segment()` to undo the segmentation, and such that `undo = +Inf` means that no changepoints will be identified. The latter case allows you to effectively skip the segmentation but still calculate all the CBS statistics across a set of known segments via `segmentByCBS(..., undo = +Inf, knownSegments = knownSegments)`. Arguments `undoTCN` and `undoDH` to `segmentByPairedPSCBS()` are adjusted analogously. Corresponding system tests were added. # Version 0.28.3 [2012-08-30] ## Code Refactoring * Updated code and Rd cross reference to use the **matrixStats** package for `weightedMedian()`, which used to be in **aroma.light**. # Version 0.28.2 [2012-08-20] ## Bug Fixes * `segmentByNonPairedPSCBS()` forgot to specify namespace **aroma.light** when trying to call `findPeaksAndValleys()`. # Version 0.28.1 [2012-08-15] ## Documentation * Minor grammatical corrections of the Paired PSCBS vignette. # Version 0.28.0 [2012-07-22] ## New Features * Added argument `minLength` to `gapsToSegments()`. The default is no longer to drop zero-length (`minLength == -1L`) segments, because if (and only if) such a segment contains a locus, then `segmentByNnn()` will currently generate an (internal) error. ## Bug Fixes * GENERALIZATION: Now `segmentByPairedPSCBS()` drops loci for which CT is missing (regardless of betaT). For instance, in rare cases when the reference (e.g. the normal) is missing, then it may be that CT is missing while betaT is not. # Version 0.27.4 [2012-07-22] ## New Features * Now verbose output of `segmentByPairedPSCBS()` specifies region ranges with greater precision. # Version 0.27.3 [2012-07-10] ## Documentation * Minor updates to the Paired PSCBS vignettes. ## Code Refactoring * CLEANUP: One redundancy tests relied on a non-critical function that will be removed in **R.utils** 1.16.0 (now in **R.devices** 2.1.1). # Version 0.27.2 [2012-07-08] ## Code Refactoring * Updated package dependencies. # Version 0.27.1 [2012-07-02] ## New Features * Now we refer to "copy neutral" segments as "neutral TCN" segments with acronym `NTCN`. The corresponding column in the segmentation results are labeled correspondingly. The Paired PSCBS vignette was updated accordingly. # Version 0.27.0 [2012-06-24] ## Documentation * Some grammar corrections of the `Paired PSCBS` vignette. ## Code Refactoring * (An update that should be ignored) # Version 0.26.1 [2012-06-05] ## New Features * Now `segmentByCBS()` for `data frame`:s does a better job identifying the CN signals. # Version 0.26.0 [2012-06-03] ## New Features * Now argument `delta` for `callCopyNeutralByTCNofAB()` of `PairedPSCBS` is calculated via `estimateDeltaCN()`, which estimates the width of the acceptance regions, used for calling copy neutral states, to be a function of the normal contamination. ## Documentation * Added details to the Paired PSCBS vignette on how to call segments that are copy neutral (typically diploid). # Version 0.25.3 [2012-06-03] ## Bug Fixes * `all.equal(target, current)` for `CBS` objects would give an error if either `target` or `current` had zero segments. # Version 0.25.2 [2012-05-30] ## New Features * Added `writeSegments()` for `DNAcopy` objects. ## Bug Fixes * `as.CNA()` for `DNAcopy` added incorrect chromosome splitters. * `as.CNA()` for `DNAcopy` would ignore argument `sample` and always return the first sample. # Version 0.25.1 [2012-05-30] ## New Features * Now `callROH()` records parameter `deltaROH` in the results. ## Documentation * Added details to the Paired PSCBS vignette on how to tune the various callers. ## Bug Fixes * `callLOH(..., force = TRUE)` would append multiple `lohCall` columns, if called multiple times. # Version 0.25.0 [2012-04-20] ## New Features * Added a trial (very much true) version of `segmentByNonPairedPSCBS()`. # Version 0.24.0 [2012-04-20] ## New Features * Now it is possible to skip the DH segmentation in Paired PSCBS, i.e. `segmentByPairedPSCBS(..., flavor = "tcn")`. # Version 0.23.2 [2012-04-20] ## Bug Fixes * `segmentByPairedPSCBS()` would throw `error in $<-.data.frame (*tmp*, "rho" ...` if some loci had unknown genomic positions. # Version 0.23.1 [2012-04-20] ## New Features * Added RSP report for `CBS` objects (adopted from ditto for `PairedPSCBS`). ## Documentation * Updated the `Paired PSCBS` vignette. # Version 0.23.0 [2012-03-20] ## Documentation * Added a package vignette. # Version 0.22.2 [2012-02-29] ## Bug Fixes * `plotTracks(..., add = TRUE)` for `PairedPSCBS` would add TCNs when BAFs and DHs were intended. # Version 0.22.1 [2012-02-28] * Updated package dependencies to **R.rsp** (>= 0.7.3) so that `report()` for `PairedPSCBS` no longer require non-public packages. ## New Features * Now it is possible to turn off usage of the alpha channel in plots generated by `report()`, which can be handy on systems where the default PNG device does not support the alpha channel. Example: `setOption("PSCBS::report/useAlphaChannel", FALSE)`. # Version 0.22.0 [2012-02-27] ## New Features * Added `report()` for `PairedPSCBS`. # Version 0.21.0 [2012-02-27] ## New Features * Added argument `fields` to `getLocusData()` for `PairedPSCBS`. * Added `renameChromosomes()` to `AbstractCBS`. # Version 0.20.0 [2012-02-26] ## New Features * Added alpha version of `callGainNeutralLoss()` for `PairedPSCBS`, which certainly will be updated in the future. This caller is tested by the system tests. * Added `dropChangePoints()` for `AbstractCBS`. ## Bug Fixes * `extractSegments()` for `PairedPSCBS` would return incorrect row indices, more precisely, overlapping data chunks. * `bootstrapTCNandDHByRegion()` for `PairedPSCBS` would resample from a subset of the intended TCNs, iff the DH mean was non-finite while there were still heterozygous SNPs. This introduced a bias in the estimates, which was neglectable for large segments, but for very small segments (a few loci) it could be relatively large. ## Software Quality * ROBUSTNESS: Added more sanity checks validating the correctness of what is returned by `extractSegments()` for `CBS` and `PairedPSCBS`. ## Code Refactoring * Added some internal utility functions for `PairedPSCBS` taken from the **aroma.cn** package. Some of these may become public later, but for they should be considered internal. # Version 0.19.8 [2012-02-23] ## Code Refactoring * ROBUSTNESS: Package now explicitly depends on **utils**. # Version 0.19.7 [2012-02-22] ## Bug Fixes * `findLargeGaps()` did not handle missing values for argument `chromosome`. * `segmentByCBS(..., knownSegments = knownSegments)` would incorrectly throw a sanity-check exception if `knownSegments` contains a segment with `start` and `stop` positions being equal. * Argument `calls` of `plotTracks()` for `PairedPSCBS` was ignored if more than one chromosome was plotted. # Version 0.19.6 [2012-01-24] ## New Features * ROBUSTNESS: Now `getCallStatistics()` for `CBS` asserts that calls have been made. If not, an exception is thrown. # Version 0.19.5 [2012-01-21] ## Documentation * Added details to the help of `callLOH()` and `callAB()` on the difference between (AB,LOH) = (TRUE,FALSE) and (AB,LOH) = (TRUE,NA). * Corrected some of verbose messages of `estimateDeltaLOHByMinC1ForNonAB()` for `PairedPSCBS` objects. # Version 0.19.4 [2012-01-10] ## Code Refactoring * Now `example(segmentByPairedPSCBS)` and the system tests that are run by `R CMD check` are tuned to (by default) run much faster by segmenting using fewer data points and bootstrapping using fewer samples. This update was done to meet the new CRAN policy. By setting environment variable `_R_CHECK_FULL_` to `1` the full data set is used instead. # Version 0.19.3 [2012-01-09] ## New Features * ROBUSTNESS: Now `extractSegments()` for `PairedPSCBS` gives an informative error message that it is not supported if CNs were segmented using flavor `"tcn,dh"`. ## Bug Fixes * `postsegmentTCN()` for `PairedPSCBS` could generate an invalid `tcnSegRows` matrix, where the indices for two consecutive segments would overlap, which is invalid. Thanks to Minya Pu for reporting on failed sanity check related to this. # Version 0.19.2 [2011-12-29] * ROBUSTNESS: Explicitly added **digest** to the list of suggested packages. # Version 0.19.1 [2011-12-13] ## New Features * Added support for `callGainsAndLosses(..., method = "ucsf-dmad")` for `CBS` objects. # Version 0.19.0 [2011-12-12] ## New Features * Added optional argument `indices` to `getLocusData()` to be able to retrieve the locus-level data as indexed by input data. ## Bug Fixes * `gapsToSegments()` gave invalid segments for chromosomes with more than one gap. Now `gapsToSegments()` validates argument `gaps` and asserts that it returns non-overlapping segments. ## Documentation * Clarified in `help("segmentByCBS")` how missing values are dealt with. # Version 0.18.2 [2011-12-07] ## New Features * Now `plotTracks()` for `CBS` always returns an invisible object. ## Bug Fixes * `pruneBySdUndo()` for `CBS` did not work with more than one array. # Version 0.18.1 [2011-12-03] ## New Features * Added `drawChangePoints()` for `AbstractCBS`. * Now `pruneByHClust()` for `AbstractCBS` updates the segment means. * Added `writeSegments()` for `PSCBS` object. * Now `print()` for `AbstractCBS` returns `getSegments(..., simplify = TRUE)`. * Added argument `simplify` to `getSegments()`. * Added arguments `name`, `tags` and `exts` to `writeSegments()` and `writeLocusData()` and dropped `filename`. # Version 0.18.0 [2011-11-28] ## New Features * Added `pruneByHClust()` for `AbstractCBS`, with implementation for `CBS` and `PairedPSCBS`. * `extractCNs()` for `CBS` would not return a matrix but a data.frame. ## Bug Fixes * `extractTotalCNs()` for `CBS` would give an error. # Version 0.17.4 [2011-11-26] ## New Features * Added argument `updateMeans = TRUE` to `callROH()` for `PairedPSCBS`. * Now `bootstrapTCNandDHByRegion()` for `PairedPSCBS` preserves NAs for DH and (C1,C2) quantiles, if the DH mean level is NA, which can happen when a segment is called ROH. This also makes sure that a segment called ROH will not be called AB. * An internal sanity check of `bootstrapTCNandDHByRegion()` for `PairedPSCBS` would give an error if DH mean levels had been set to NA for segments called ROH. # Version 0.17.3 [2011-11-24] ## New Features * Added `callSegmentationOutliers()` and `dropSegmentationOutliers()` for data frames. * CLEANUP: Renamed field `position` of the example data to `x`. This helps us clean up some of the examples. ## Bug Fixes * `bootstrapTCNandDHByRegion()` for `PairedPSCBS` would give an error, if a segment did not have any TCN signals, which can occur when known segments are specified for Paired PSCBS. # Version 0.17.2 [2011-11-22] ## New Features * Added `findLargeGaps()` and `gapsToSegments()`. # Version 0.17.1 [2011-11-21] ## Bug Fixes * The internal sanity check of `testROH()` on weights was slightly too conservative (required to high precision) when it came to asserting that the sum of the weights equals one. * `resegment()` for `PairedPSCBS` called `segmentByCBS()` instead of `segmentByPairedPSCBS()`. # Version 0.17.0 [2011-11-19] ## New Features * Now it is possible to run Paired PSCBS (without TumorBoost) when only genotypes but not BAFs are available for the matched normal. # Version 0.16.3 [2011-11-17] ## New Features * Added `resegment()` for `CBS` and `PairedPSCBS` for easy resegmentation. * Adjusted `segmentByCBS()` such that it can handle `knownSegments` with chromosome boundaries given as -Inf and +Inf. * Now argument `mar` for `plotTracks()` defaults to NULL. * ROBUSTNESS: Added redundancy tests for `segmentByCBS()` and `segmentByPairedPSCBS()` with argument `knownSegments`. * ROBUSTNESS: Now `segmentByCBS()` does more validation of `knownSegments`. * FIX: `extractRegions()` for `AbstractCBS` would also show verbose output. ## Bug Fixes * Now argument/parameter `seed` is correctly preserved by `segmentByCBS()`. So is `tbn` for `segmentByPairedPSCBS()`. * `segmentByPairedPSCBS()` would give an error when trying to segment DH if the TCN segment contains no data points, which could happen if `knownSegments` specifies an empty segment, e.g. centromere. * `extractSegments()` for `CBS` would throw an error when there were multiple chromosomes. # Version 0.16.2 [2011-11-16] ## New Features * Now `segmentByCBS(..., w)` stores weights `w`, if given, in the locus-level data table of the returned CBS object. * Added `pruneBySdUndo()` for `CBS`, which does what `undo.splits = "sdundo"` for `DNA::segment()`, but on the already segmented results. * Now `updateMeans()` uses locus-specific weights, iff available. * Added `updateBoundaries()` for `CBS` to update (start,stop) per segment. * CORRECTNESS: Now `updateMeans()` for `CBS` identifies loci via internal `segRows` field and no longer by locations of segment boundaries, which gave slightly incorrect estimates for "tied" loci. # Version 0.16.1 [2011-11-15] ## New Features * Now more segmentation parameters are stored in the `CBS` object. * SPEEDUP: Now `segmentByCBS()` will use memoization to retrieve so called "sequential boundaries for early stopping", iff any of the `DNAcopy::segment()` arguments `alpha`, `nperm` and `eta` are specified. See also `DNAcopy::getbdry()`. * Added `method = "DNAcopy"` to `estimateStandardDeviation()` for `CBS`, which estimates the std. dev. using `DNAcopy:::trimmed.variance()`. ## Bug Fixes * `extractSegments()` for `CBS` would throw an error, because in most cases it would created a corrupt internal `segRows` field. # Version 0.16.0 [2011-11-12] ## New Features * Added argument `oma` and `mar` to `plotTracksManyChromosomes()` for `PairedPSCBS` for setting graphical parameters when `add = FALSE`. * Added `callROH()`. * Added arguments `from` and `adjustFor` to `updateMeans()`. # Version 0.15.5 [2011-11-04] ## Bug Fixes * `extractSegment()` for `AbstractCBS` would give an error, because it called itself instead of `extractSegments()`. # Version 0.15.4 [2011-10-30] ## New Features * Added `save()` and `load()` methods to `AbstractCBS`, which are wrappers for `saveObject()` and `loadObject()` that assert the correct class structure. Also, the `load()` method will automatically update the class hierarchy for `CBS` and `PairedPSCBS` objects that were saved before adding class `AbstractCBS`. # Version 0.15.3 [2011-10-23] ## Bug Fixes * `callAmplifications()` for `CBS` generated an error, if more than one chromosome were called. * The length of a segment must be defined as 'end-start' and not 'end-start+1' so that the the total length of all segments adds up correctly. * `highlightArmCalls()` for `CBS` did not handle empty chromosomes. * `getCallStatisticsByArms()` for `CBS` threw a error if argument `genomeData` did not contain exactly the same chromosomes as in the `CBS` object. # Version 0.15.2 [2011-10-21] ## New Features * Added `mergeThreeSegments()` for `AbstractCBS`. ## Bug Fixes * Recent updates caused `segmentByPairedPSCBS(data)` not to work when `data` is a data frame. # Version 0.15.1 [2011-10-21] ## New Features * By setting `start` and `end` to NAs in `knownSegments` (chromosome must still be specified), it is possible to insert an empty segment that disconnects the two flanking segments, e.g. centromere and the two arms. # Version 0.15.0 [2011-10-20] ## New Features * Added support for specifying priorly known segments, such as chromosome arms and centromeres, in `segmentByCBS()` via argument `knownSegments`. ## Bug Fixes * CLEANUP: Dropped a stray debug output message in `segmentByPairedPSCBS()`. # Version 0.14.3 [2011-10-17] ## New Features * Added argument `asMissing` to `dropRegions()` for `AbstractCBS`. # Version 0.14.2 [2011-10-16] ## New Features * Implemented `extractCNs()` for `CBS` and `PairedPSCBS`. * Added `extractTotalCNs()` for `CBS`. # Version 0.14.1 [2011-10-14] ## New Features * Added implementation of `extractRegions()` for `AbstractCBS`, which utilizes `extractSegments()`. * Added abstract `extractSegments()` and `extractSegment()` for `AbstractCBS`. * Now `extractTCNAndDHs()` for `PairedPSCBS` passes `...` to `getSegments()`. # Version 0.14.0 [2011-10-10] ## Code Refactoring * CLEANUP: Harmonization of several method names. * CLEANUP: Internal restructuring of the source code files. # Version 0.13.5 [2011-10-10] ## New Features * Added `dropChangePoint()` for `AbstractCBS`, which is just a "name wrapper" for `mergeTwoSegments()`. * Added `dropRegion()` and `dropRegions()` for `AbstractPSCBS`, where the former is a wrapper for the latter `dropRegions()`. * Added `updateMeans()` and `mergeTwoSegments()` for `CBS` in addition already available `PairedPSCBS` versions. * Relabeled column `id` to `sampleName` returned by `getSegments()`. ## Bug Fixes * For so called "splitter" rows, not all columns returned by `getSegments()` of `CBS` were missing values. * The object returned by `as.CBS()` for `DNAcopy` did not have the correct class hierarchy. ## Code Refactoring * ROBUSTNESS: Now using `getSegments()` everywhere possible. # Version 0.13.4 [2011-10-08] ## New Features * Added `all.equal()` for `AbstractCBS`, which does not compare attributes. * Added optional argument `regions` to `getCallStatistics()` for `CBS` in order to calculate call statistics on subsets of chromosomes, e.g. chromosome arms. * Added `drawChromosomes()` for `CBS`. * Added `getCallStatisticsByArms()`, `callArms()`, and `highlightArmCalls()` for `CBS` objects. ## Code Refactoring * Now internal `getChromosomeRanges()` of `CBS` returns a data.frame instead of a matrix, and first column is now `chromosome`. # Version 0.13.3 [2011-10-03] ## New Features * GENERALIZATION: Now `segmentByCBS()` and `segmentByPairedPSCBS()` also accepts a data.frame of locus-level data with column names matching the locus-level arguments accepted by the corresponding method. * GENERALIZATION: Now all segmentation result classes (`CBS` and `PSCBS`) inherits from the `AbstractCBS` class, which provides methods such as `getSampleName()`, `getChromosomes()` and `getSegments()`. ## Documentation * Added lots of more help pages. ## Code Refactoring * CLEANUP: Dropped empty `callSegments()` for `PairedPSCBS`. # Version 0.13.2 [2011-09-30] ## New Features * GENERALIZATION: Now `drawLevels()` for `PairedPSCBS` allows for drawing segmentation results in 'betaT' space. ## Bug Fixes * `plotTracks2(..., panels = "dh")` gave an error due to a forgotten assignment. # Version 0.13.1 [2011-09-06] ## New Features * Added formal class `CBS`, which holds the segmentation results returned by `segmentByCBS()`. Several methods are available for `CBS` objects, e.g. `nbrOfLoci()`, `nbrOfSegments()`, `nbrOfChromosomes()`, `getChromosomes()`, `estimateStandardDeviation()`, etc. * Now `segmentByCBS()` always returns a `CBS` object. To coerce to a `DNAcopy` object (as defined in the `DNAcopy` class) use `as.DNAcopy()`. * Added coerce methods `as.DNAcopy()` for `CBS` objects and `as.CBS()` for `DNAcopy` objects. # Version 0.13.0 [2011-09-01] ## New Features * GENERALIZATION: Now `segmentByCBS()` can process multiple chromosomes. * Added `append()` for `CBS` objects. ## Bug Fixes * Internal methods `plotTracksManyChromosomes()` and `tileChromosomes()` for `CBS` did not work at all and therefore neither `plotTracks()` for `CBS` with more than one chromosome. # Version 0.12.2 [2011-08-27] ## Code Refactoring * CLEANUP: Now `R CMD check` is no longer giving a note that the package loads package **DNAcopy** in `.onAttach()`. # Version 0.12.1 [2011-08-08] ## Bug Fixes * If `dropSegmentationOutliers()` would drop an outlier next to a change point, such that the total copy-number signal becomes NA, then the sanity checks that TCN segments always overlaps DH segments would fail. Now the sanity checks are aware of this special case. These sanity checks were moved from `bootstrapTCNandDHByRegion()` to `segmentByPairedPSCBS()`. Thanks Christine To at University of Toronto for reporting on this. # Version 0.12.0 [2011-07-23] ## Bug Fixes * Recently R devel automatically adds a namespace to a package, if missing. This caused some of the **PSCBS** examples to throw an exception related to incorrect dispatching of `cat()`. ## Code Refactoring * Added a namespace to the package, which will be more or less a requirement in the next major release of R. # Version 0.11.7 [2011-07-15] ## Documentation * Added a section to `help("segmentByPairedPSCBS")` on the importance of doing a whole-genome PSCBS segmentations if calling AB and LOH states afterward. * Made it more clear in `help("segmentByPairedPSCBS")` that arguments `betaT`, `betaN` and `muN` may contain NAs for non-polymorphic loci. # Version 0.11.6 [2011-07-14] ## Bug Fixes * ROBUSTNESS: In some cases, the segmentation table would contain column names with incorrect capitalization, e.g. `tcnnbrOfLoci` instead of `tcnNbrOfLoci`. This would cause several downstream methods to give an error. The reason for this is that the **Hmisc** package, if loaded after **R.utils**, overrides `capitalize()` in **R.utils** with another (buggy?) `capitalize()` function. To avoid this, we now everywhere specify explicitly that we want the one in **R.utils**. Thanks Christine To at University of Toronto for reporting on this. # Version 0.11.5 [2011-07-10] ## Bug Fixes * `tileChromosomes()` for `PairedPSCBS` was still assuming the old naming convention of column names. This caused `plotTracks()` to throw an exception when plotting multiple chromosomes. ## Code Refactoring * ROBUSTNESS: Fixed partial argument matchings in `arrowsC1C2()` and `arrowsDeltaC1C2()` for `PairedPSCBS`. # Version 0.11.4 [2011-07-07] ## New Features * GENERALIZATION: Now the internal estimator function that `estimateDeltaLOH()` uses returns -Inf if all segments are called AB, instead of throwing an exception. This will in turn make `callLOH()` call all segments to be non-LOH. ## Documentation * Removed obsolete references to the R-forge repository. ## Bug Fixes * Consecutive calls to `callAB(..., force = TRUE)` would append additional `abCall` columns to the segmentation table instead of replacing existing calls. # Version 0.11.3 [2011-07-06] ## New Features * ROBUSTNESS: Added a sanity check to `estimateDeltaLOHByMinC1AtNonAB()` for `PairedPSCBS` object. The test asserts that there exist segments that are not in allelic balance, which are needed in order to estimate DeltaLOH. ## Documentation * The description of argument `chromosome` for `segmentByPairedPSCBS()` did not describe how to segment multiple chromosomes in one call. # Version 0.11.2 [2011-07-05] ## Bug Fixes * Output fields `tcnNbrOfSNPs` and `tcnNbrOfHets` were mistakenly labeled as `tcnNbrOr...`. Thanks Christine Ho at UC Berkeley for reporting on this. # Version 0.11.1 [2011-06-28] ## Documentation * Clarified that argument `CT` should be tumor copy number ratios relative to the normal. * Added Rd help for `as.data.frame()` of `PairedPSCBS`. # Version 0.11.0 [2011-06-14] ## Significant Changes * Renamed all column names of returned data frames such that they follow the camelCase naming conventions in addition to be somewhat shorter too. ## New Features * GENERALIZATION: Added argument `columnNamesFlavor` to `segmentByCBS()`. # Version 0.10.2 [2011-06-07] ## Code Refactoring * CLEANUP: Cleaned up the `example()`:s. * Added more `biocViews` categories to DESCRIPTION. # Version 0.10.1 [2011-05-31] ## New Features * GENERALIZATION: The package can now be _installed_ without the **DNAcopy** package being installed. If package is loaded without **DNAcopy** installed, an informative message will explain how to install it. * Added `installDNAcopy()`, which will install **DNAcopy** from Bioconductor. ## Code Refactoring * ROBUSTNESS: Now all **DNAcopy** functions are called as `DNAcopy::nnn()`. # Version 0.10.0 [2011-05-29] ## Significant Changes * Renamed package to **PSCBS** (from **psCBS**). * Renamed all arguments, variables, and functions referring to `tau` to refer to `delta` reflecting the notation of the Paired PSCBS paper. * Renamed options, example code and help pages to reflect new package name. ## Documentation * Updated references in help pages. * Now the paired PSCBS is formally referred to as 'Paired PSCBS'. # Version 0.9.54 [2011-04-27] ## New Features * Added argument `maxC` to `estimateTauLOHByMinC1ForNonAB()`. # Version 0.9.53 [2011-04-14] * Added argument `max` to `estimateTauAB()` and `estimateTauLOH()`. # Version 0.9.52 [2011-04-14] ## Bug Fixes * Argument `minSize` of `callAB()` and `callLOH()` had no effect. # Version 0.9.51 [2011-04-12] ## New Features * Added argument `minSize` to `callAB()` and `callLOH()` for `PairedPSCBS`. * Now the a conflicting call in `callLOH()`/`callAB()` with argument `xorCalls = TRUE` is set to NA to contrast it from a FALSE call. # Version 0.9.50 [2011-04-12] ## New Features * Added argument `xorCalls` to `callLOH()` and `callAB()` for `PairedPSCBS`. When TRUE (the default), a segment that is already called AB will never be called LOH, and vice versa. # Version 0.9.49 [2011-04-11] ## New Features * Updated `estimateTauABBySmallDH()` for `PairedPSCBS` to use a "symmetric" quantile estimator. * Added argument `midpoint` to `estimateTauLOHByMinC1AtNonAB()`. ## Bug Fixes * The recent `callLOH()` would not store the LOH calls. # Version 0.9.48 [2011-04-10] ## New Features * Added `callLOH()` for `PairedPSCBS`, which in turn calls auxiliary methods. * Added `estimateTauLOH()` for `PairedPSCBS`, which in turn calls auxiliary methods. * Now `callAB(..., force = FALSE)` skips the caller if allelic-balance calls already exist. ## Documentation * Update the example for `segmentByPairedPSCBS()` to reflect the restructured AB and LOH callers. # Version 0.9.47 [2011-04-08] ## New Features * Added `estimateTauABBySmallDH()`. * Added internal `weightedQuantile()`. ## Documentation * Added help pages for more methods. ## Code Refactoring * CLEANUP: Started to restructure the source code files. # Version 0.9.46 [2011-04-08] ## Bug Fixes * `postsegmentTCN()` for `PairedPSCBS` could generate an invalid `tcnSegRows` matrix, where the indices for two consecutive segments would overlap, which is invalid. This was caught with real data, but it seems to have required a very rare combination of data in order for it to occur. # Version 0.9.45 [2011-04-05] ## Bug Fixes * `estimateHighDHQuantileAtAB()` for `PairedPSCBS` would throw an error on an undefined `trim` if verbose output was used. # Version 0.9.44 [2011-02-18] ## New Features * Added `estimateHighDHQuantileAtAB()` for `PairedPSCBS`. # Version 0.9.43 [2011-02-06] ## Bug Fixes * `plotTracks2()` queried non-existing argument `tracks`. # Version 0.9.42 [2011-02-03] ## New Features * Added `estimateKappa()` for estimating the normal contamination. # Version 0.9.41 [2011-02-02] ## Significant Changes * Updated default for `tauAB` of `callABandHighAI()` and `callABandLowC1()` to be estimated from data using `estimateTauAB()`. ## New Features * Added argument `tauTCN` to `estimateTauAB()`. # Version 0.9.40 [2011-01-27] ## New Features * Added argument `flavor` to `estimateTauAB()` for estimating the AB threshold using alternative methods. # Version 0.9.39 [2011-01-19] ## New Features * Added trial version of new `plotTracks2()`, which will later replace `plotTracks()`. Currently it only works for single chromosomes. * Added support functions, e.g. `updateMeans()`. # Version 0.9.38 [2011-01-18] ## New Features * Added arguments `changepoints` and `col` to `plotTracks()` for `PairedPSCBS`. * Now `plotTracks(..., add = FALSE)` for `PairedPSCBS` only sets up subplots if argument `tracks` specifies more than one panel. ## Documentation * Documented more `plotTracks()` arguments for `PairedPSCBS`. ## Bug Fixes * Now `plotTracks(..., add = TRUE)` for `PairedPSCBS` plots to the current figure/panel. # Version 0.9.37 [2011-01-18] ## Bug Fixes * `tcnSegRows` and `dhSegRows` where not updated by `extractByRegions()` for `PairedPSCBS`. # Version 0.9.36 [2011-01-14] ## New Features * Added `estimateTauAB()` for estimating the tauAB tuning parameter when calling segments in allelic balance. Updated `example(segmentByPairedPSCBS)` to illustrate how to use it. * Added `extractByRegions()` for `PairedPSCBS`. # Version 0.9.35 [2011-01-12] ## New Features * Now `postsegmentTCN(..., force = TRUE)` for `PairedPSCBS` also updates the TCN estimates even for segments where the DH segmentation did not find any additional change points. # Version 0.9.34 [2010-12-09] ## Bug Fixes * When there were multiple chromosomes processed by `segmentByPairedPSCBS()`, then the returned data object would contain `betaT` identical to `betaTN`. # Version 0.9.33 [2010-12-07] ## New Features * Added `callLowC1ByC1()` and `callABandLowC1()`. # Version 0.9.32 [2010-12-03] ## Bug Fixes * In rare cases the bootstrap sanity checks can indeed produce an invalid `range`, more precisely where (`range[,2]` >= `range[,1]`) is not true. This can happen if there is no variation in the bootstrap estimates. Because of this we allow for some tolerance. # Version 0.9.31 [2010-12-02] ## New Features * Added option `psCBS/sanityChecks/tolerance` for specifying the tolerance of some internal sanity checks. # Version 0.9.30 [2010-12-01] ## Code Refactoring * Rewrote all code dealing with the identification of loci belong to segments. The code is now utilizing the `segRows` element returned by `DNAcopy::segment()`. Lots of the code was rewritten and therefore completely new bugs may have been introduced. # Version 0.9.25 [2010-11-30] ## Bug Fixes * Argument `flavor` of `segmentByPairedPSCBS()` would be ignored if multiple chromosomes were segmented. * `extractByChromosome()` for `PSCBS` would call it self instead of `extractByChromosomes()`. # Version 0.9.24 [2010-11-28] ## Bug Fixes * `postsegmentTCN()` did not handle loci with the same positions and that are split in two different segments. It also did not exclude loci with missing values. # Version 0.9.23 [2010-11-28] ## Bug Fixes * The algorithm in `segmentByCBS()` that infers which loci (of the ones share the same genomic positions) that should be exclude from each segment did not take missing signals into account. * Iff argument `chromosome` to `segmentByPairedPSCBS()` was of length greater than one and specified exactly one unique chromosome, then exception `Number of elements in argument 'chromosome' should be exactly 8712 not 86209 value(s)` would be thrown. # Version 0.9.22 [2010-11-27] ## Bug Fixes * `bootstrapTCNandDHByRegion()` would incorrectly include non-polymorphic loci in the set of homozygous SNPs during resampling. * `segmentByPairedPSCBS()` would not accept missing values in argument `chromosome`. # Version 0.9.21 [2010-11-27] ## New Features * Now arguments `...` of `segmentByPairedPSCBS()` are passed to the two `segmentByCBS()` calls. * Added `callSegmentationOutliers()`, which can be used to identify single-locus outliers that have a genomic signal that is clearly outside the expected range. The `dropSegmentationOutliers()` sets locus outliers detected by this method to missing values. This is useful for excluding total copy-number outliers that otherwise can have a dramatic impact on the non-robust CBS method. # Version 0.9.20 [2010-11-26] ## New Features * Added optional argument `chromosomes` to `plotTracks()` to plot a subset of all chromosomes. * Added `extractByChromosomes()` for `PSCBS`. * Now the default confidence intervals for `plotTracks()` is (0.05,0.95), if existing. * Now all call functions estimate symmetric bootstrap quantiles for convenience of plotting confidence intervals. ## Bug Fixes * `callABandHighAI()` for `PairedPSCBS` used the old DH-only bootstrap method. * The statistical sanity checks of the bootstrap estimates would give an error when only single-sided bootstrap confidence interval was calculated. * The call functions, for instance `callABandHighAI()`, would throw `Error in quantile.default(x, probs = alpha) : missing values and NaN's not allowed if 'na.rm' is FALSE`, unless `bootstrapTCNandDHByRegion()` was run before. # Version 0.9.19 [2010-11-23] ## New Features * ROBUSTNESS: Added more sanity checks to `bootstrapTCNandDHByRegion()`. * WORKAROUND: The precision of the mean levels of `DNAcopy::segment()` is not great enough to always compare it to that of R's estimates. ## Bug Fixes * `bootstrapTCNandDHByRegion()` would give an error if there was only one segment. * `segmentByPairedPSCBS()` and `bootstrapTCNandDHByRegion()` would not subset the correct set of DH signals if there were some missing values in TCN. # Version 0.9.18 [2010-11-22] ## New Features * Added argument `calls` to `plotTracks()` for highlighting called regions. * Updated `callAllelicBalanceByDH()` and `callExtremeAllelicImbalanceByDH()` to utilize `bootstrapTCNandDHByRegion()`. * ROBUSTNESS: Now `drawConfidenceBands()` of `PairedPSCBS` silently does nothing if the requested bootstrap quantiles are available. ## Bug Fixes * `bootstrapTCNandDHByRegion()` for `PairedPSCBS` would not correctly detect if bootstrap results are already available. # Version 0.9.17 [2010-11-21] ## New Features * Now `plotTracks()` supports tracks `"tcn,c1"`, `"tcn,c2"`, and `"c1,c2"` too. * Added support for flavor `"tcn&dh"` in `segmentByPairedPSCBS()`, which contrary to `"tcn,dh"` enforces TCN and DH to have the same change points. The default flavor is now `"tcn&dh"`. * Added argument `xlim` to `plotTracks()` making it possible to zoom in. # Version 0.9.16 [2010-11-21] ## New Features * Now `joinSegments = TRUE` is the default for `segmentByCBS()` and `segmentByPairedPSCBS()`. * Added argument `quantiles` to `plotTracks()`, which if specified draws confidence bands previously estimated from bootstrapping. * Added `drawConfidenceBands()` for `PairedPSCBS`. * Added `bootstrapTCNandDHByRegion()` for `PairedPSCBS`. * Added standalone `joinSegments()` for `CBS` results. * Now `segmentByPairedPSCBS()` also returns minor and major copy numbers for each segment. # Version 0.9.15 [2010-11-21] ## New Features * Adjusted `postsegmentTCN()` such that the updated TCN segment boundaries are the maximum of the DH segment and the support by the loci. This means that `postsegmentTCN()` will work as expected both when signals where segmented with `joinSegments` being TRUE or FALSE. * Updated `plotTracks()` for `PairedPSCBS` such that the TCN segmentation is colored 'purple' and the DH segmentation 'orange' for TCN and DH only tracks. # Version 0.9.14 [2010-11-20] ## New Features * Now it is possible to specify the boundaries of the regions to be segmented as known change points via argument `knownCPs`. * Added argument `joinSegments` to `segmentByCBS()` and `segmentByPairedPSCBS()` in order to specify if neighboring segments should be joined or not. * Now `segmentByCBS()` and `segmentByPairedPSCBS()` allow for unknown genomic positions as well as missing total CN signals. # Version 0.9.13 [2010-11-19] ## New Features * Added argument `joinSegments` to `segmentByCBS()` in order to specify if neighboring segments should be joined or not. # Version 0.9.12 [2010-11-19] ## New Features * Added `plotTracks()` and `drawLevels()` etc. to CBS results. * Now `segmentByCBS()` allows for unknown genomic positions. * Now `segmentByCBS()` allows for missing signals. * Added argument `preserveOrder` to `segmentByCBS()`. If TRUE, then the loci in the returned `data` object are ordered as the input data, otherwise it is ordered along the genome. # Version 0.9.11 [2010-11-16] ## New Features * Now the `data` object returned by `segmentByCBS()` contains field `index` if and only if the loci had to be reorder along the genome. ## Documentation * Added more details, references to papers, and cross links to other functions to the help pages. ## Bug Fixes * In the rare cases where two loci at the same positions are split up into two neighboring segments, then `segmentByPairedPSCBS()` would fail to infer which they were if and only if the loci were not ordered along the genome. This could happen with for instance Affymetrix `GenomeWideSNP_6` data. # Version 0.9.10 [2010-11-09] ## New Features * Added argument `cex = 1` to `plotTracks()`. ## Bug Fixes * It was not possible to plot BAF tracks with `plotTracks()`. # Version 0.9.9 [2010-11-05] ## Bug Fixes * `segmentByCBS()` tried to pass non-existing argument `undo.split` to `DNAcopy::segment()`. It should be `undo.splits`. # Version 0.9.8 [2010-11-04] ## Bug Fixes * There was a stray/debug `stop()` statement left in `segmentByPairedPSCBS()` causing an "error" in the rare case when loci that have the same physical locations are split into two different segments. # Version 0.9.7 [2010-11-03] * ROBUSTNESS: Now `bootstrapDHByRegion()` uses `resample()` of **R.utils**. ## Bug Fixes * `bootstrapDHByRegion()` did not sample from the correct unit(s) when there was only one DH signal. # Version 0.9.6 [2010-11-02] ## New Features * Added arguments `undoTCN` and `undoDH` to `segmentByPairedPSCBS()`. * Added argument `undo` to `segmentByCBS()`, which corresponds to `undo.splits = "sdundo"` and `undo.SD = undo`, if undo < +Inf. ## Bug Fixes * Arguments `alphaTCN` and `alphaDH` of `segmentByPairedPSCBS()` were not used when more than one chromosome were segmented. # Version 0.9.5 [2010-11-01] ## New Features * Added arguments `alphaAB` and `alphaHighAI` to `callABandHighAI()`. ## Bug Fixes * `bootstrapDHByRegion()` would give an error if only a single quantile was requested. * `bootstrapDHByRegion()` would give `Error in if (nbrOfUnits > segJJ[, "dh.num.mark"]) { : missing value where TRUE/FALSE needed` when `dh.num.mark` was NA. # Version 0.9.4 [2010-10-25] ## New Features * Now the default is a 95% confidence interval for calls. * Now `segmentByCBS()` also returns element `lociNotPartOfSegment`, if there are segments that share end points, which can happen if a change point is called in middle of a set of loci that have the same genomic positions. In such cases, `lociNotPartOfSegment` specifies which loci are *not* part of which segment. Then by identifying the loci that are within a segment by their positions and excluding any of the above, one knows exactly which loci CBS included in each segment. ## Bug Fixes * Now `bootstrapDHByRegion()` for `PairedPSCBS` handles the rare case when markers with the same positions are split in two different segments. * Now the correct set of loci are extracted from each TCN segment, in the rare case that two neighboring TCN segments have the same end points. # Version 0.9.3 [2010-10-25] ## New Features * Added argument `ciRange` to `callAllelicBalance()` and `callExtremeAllelicImbalance()`. ## Bug Fixes * `bootstrapDHByRegion()` for `PairedPSCBS` would bootstrap from the incorrect set of loci when the DH region contained only one locus. * `bootstrapDHByRegion()` for `PairedPSCBS` would bootstrap from the incorrect set of loci if more than one chromosome was available. # Version 0.9.2 [2010-10-24] ## Bug Fixes * `plotTracks()` would give `Error: object 'nbrOfLoci' not found` for whole-genome plots. # Version 0.9.1 [2010-10-20] ## New Features * Now `plotTracks()` can plot whole-genome data. # Version 0.9.0 [2010-10-18] ## New Features * Added arguments `alphaTCN` and `alphaDH` to `segmentByPairedPSCBS()` with defaults according to the paper. # Version 0.8.3 [2010-10-18] ## New Features * Now `segmentByPairedPSCBS()` can segment multiple chromosomes. # Version 0.8.2 [2010-10-17] ## New Features * Added argument `tbn` to `segmentByPairedPSCBS()` specifying whether TumorBoostNormalization should be applied or not. # Version 0.8.1 [2010-10-10] ## Significant Changes * The default for `segmentByPairedPSCBS()` is now to segment TCN on the original scale, not the `sqrt()`. ## New Features * Added `plotTracks()` for `PairedPSCBS`. # Version 0.8.0 [2010-10-06] ## Code Refactoring * CLEANUP: Removed all old code, native code and help pages. # Version 0.7.8 [2010-10-03] ## New Features * Added optional argument `chromosome` to `segmentByCBS()`. Note that at this point it is only used for annotating the results; it can not be used to segmented multiple chromosomes at ones. # Version 0.7.7 [2010-09-26] ## New Features * Now `subsetBySegments()` and `postsegmentTCN()` for `PairedPSCBS` handles multiple chromosomes. # Version 0.7.6 [2010-09-24] ## New Features * Added support to annotating and subsetting also by chromosomes, as well as appending segmentation results from different chromosomes together. # Version 0.7.5 [2010-09-21] ## New Features * Added `postsegmentTCN()` for `PairedPSCBS`, which updates the TCN segment start and ends, estimates and counts given the DH segments. # Version 0.7.4 [2010-09-18] ## New Features * Added argument `chromosome` to `segmentByPairedPSCBS()`, which, if given, adds a chromosome column to the data and segmentation results. ## Bug Fixes * `plot()` for `PairedPSCBS` used a non-defined variable. # Version 0.7.3 [2010-09-16] ## New Features * Added `callABandHighAI()` for calling paired PSCBS segmentation results. ## Code Refactoring * Added internal bootstrapping functions. # Version 0.7.2 [2010-09-15] ## New Features * Added more methods for the `PSCBS` class. # Version 0.7.1 [2010-09-08] ## New Features * Added more methods for the `PSCBS` class. * Now `segmentByPairedPSCBS()` also returns the TumorBoost normalized data. # Version 0.7.0 [2010-09-04] ## New Features * Updated `segmentByPairedPSCBS()` to provide two-step segmentation from first segmenting the total copy numbers and then the decrease-of-heterozygosity signals. Added utility functions for plotting the results. The code for calling allelic imbalance and LOH is still to be added. # Version 0.6.3 [2010-09-02] ## New Features * Now `segmentByCBS()` also works if there are no data points. # Version 0.6.2 [2010-07-14] ## New Features * Added `callNaiveHeterzygotes()`, which is a cleaned up version of `findheterozygous()`. Added Rd example that asserts that the two are identical and compares the calls to those of `aroma.light::callNaiveGenotypes()`. # Version 0.6.1 [2010-07-09] ## New Features * Added low-level `segmentByPairedPSCBS()`, which runs paired PSCBS segmentation on a single sample and a single chromosome. It only segments; it does not call segments. This is only a stub in the sense that it still does not adjust p-values etc. * Added low-level `segmentByCBS()`, which runs CBS segmentation on a single sample and a single chromosome. * BACKWARD COMPATIBILITY: Now `psCNA()` returns a list of length 8. * Reverted `psSegment()` back to v0.5.6. # Version 0.6.0 [2010-07-08] ## New Features * Now `psSegmentPaired()` returns a data frame (no longer a matrix). * CLEANUP: Created `psSegmentPaired()` from `psSegment()`. ## Code Refactoring * CLEANUP: Major cleanup, i.e. renaming variables, reordering etc. * ROBUSTNESS: Replaced all `1:n` with `seq(length = n)` to deal with `n == 0`. * ROBUSTNESS: Now all list elements are referenced by name. * ROBUSTNESS: Now all iterator variables are written as `ii`, `jj`, etc. * Using `setMethodS3()` of **R.methodsS3** to define S3 methods. * Dropping NAMESPACE while package is finished. This makes it easier to patch methods, etc. # Version 0.5.6 [2010-07-07] ## Documentation * Added `example(psSegment)`. ## Bug Fixes * Previous clean up introduced bugs. * The dynamic library for `hrmode()` was not loaded. # Version 0.5.5 [2010-05-05] ## Code Refactoring * CLEANUP/ROBUSTNESS: Major code clean up. # Version 0.5.4 [2010-04-30] ## Code Refactoring * Added internal `hrmode()`. * CLEANUP: Renamed source files to match function names. Only only function per source file. # Version 0.5.3 [2010-04-22] ## Significant Changes * ABO updated the psCBS algorithm. # Version 0.5.2 [2010-0?-??] * ??? # Version 0.5.1 [2010-03-31] ## Significant Changes * Now `psSegment(..., matching.reference = TRUE)` does TumorBoost normalization on the allele B fractions before segmentation. # Version 0.5.0 [2010-03-12] * Added to R-forge repository. PSCBS/inst/0000755000176200001440000000000015000517067012102 5ustar liggesusersPSCBS/inst/CITATION0000644000176200001440000000427715000516420013241 0ustar liggesusersutils::bibentry( header = "Please cite PSCBS using one or more of the following references:", # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # BibTeX entry: # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - bibtype = "Article", author = "Adam B. Olshen and Henrik Bengtsson and Pierre Neuvial and Paul Spellman and Richard A. Olshen and Venkatraman E. Seshan", title = "Parent-specific copy number in paired tumor-normal studies using circular binary segmentation", journal = "Bioinformatics", year = "2011", volume = "27", number = "15", doi = "10.1093/bioinformatics/btr329", url = "https://doi.org/10.1093/bioinformatics/btr329", # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Plain-text citation: # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - textVersion = paste(sep="", "A.B. Olshen, H. Bengtsson, P. Neuvial, P.T. Spellman, R.A. Olshen, V.E. Seshan. ", "Parent-specific copy number in paired tumor-normal studies using circular binary segmentation, ", "Bioinformatics, ", "2011" ) ) utils::bibentry( header = "Please cite PSCBS using one or more of the following references:", # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # BibTeX entry: # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - bibtype = "Article", author = "H. Bengtsson and Pierre Neuvial and Terence P Speed", title = "TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays", journal = "BMC Bioinformatics", year = "2010", month = "May", volume = "11", number = "245", doi = "10.1186/1471-2105-11-245", url = "https://doi.org/10.1186/1471-2105-11-245", # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Plain-text citation: # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - textVersion = paste(sep="", "H. Bengtsson, P. Neuvial and T.P. Speed. 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The method also calls segments with run of homozygosity (ROH), segments in allelic balance (AB) and segments with loss of heterozygosity (LOH). Paired PSCBS was designed to work with data from any SNP microarray technology and generation, including Affymetrix and Illumina. This document shows how to use the \pkg{PSCBS} package to run Paired PSCBS on a tumor-normal pair. \end{abstract} \keywords{<%@meta name="keywords"%>} \begin{center} \emph{This vignette is distributed as part of the \pkg{PSCBS} package, which is available on CRAN (\url{https://cran.r-project.org/}). The authors very much appreciate feedback on this document.} \end{center} \clearpage \tableofcontents \clearpage <%------------------------------------------------------------------- BACKGROUND -------------------------------------------------------------------%> \section{Background} \label{secBackground} We will here use a small example data set to illustrate how to setup the data in a format suitable for Paired PSCBS, how to identify segments, how to call them, and how to plot and export the segmentation results. The statistical model and the algorithm behind Paired PSCBS is explained in detail in~\citet{OlshenA_etal_2011}. <%------------------------------------------------------------------- EXAMPLE -------------------------------------------------------------------%> \section{Preparing data to be segmented} The Paired PSCBS~\citep{OlshenA_etal_2011} method requires tumor-normal paired parent-specific copy-number (PSCN) signals. More precisely, it requires total copy-number (TCN) estimates for the tumor relative to the matched normal ($C_T$), allele B fractions (BAFs) for the tumor ($\beta_T$) and BAFs for the matched normal ($\beta_N$). The genomic locations of the loci in form of chromosome and physical position are also required. \subsection{Locus-level SNP copy-number signals} \label{secData} In this example we will use a small example data set part of the \pkg{PSCBS} package. It can be loaded as: <% fullname <- "PairedPSCBS,exData,chr01" %> \begin{verbatim} <%=withCapture({ data <- PSCBS::exampleData("paired.chr01") str(data) })%> \end{verbatim} In additional to the mandatory fields (\code{chromosome}, \code{x}, \code{CT}, \code{betaT}, and \code{betaN}), this data set also contains TCNs for normal (\code{CN}) relative to a large pool of normal samples. The latter will not be used here. \subsection{Dropping TCN outliers} \label{secTCNOutliers} There may be some outliers among the TCNs. In CBS~\citep{OlshenA_etal_2004,VenkatramanOlshen_2007}, the authors propose a method for identifying outliers and then to shrink such values toward their neighbors ("smooth") before performing segmentation. At the time CBS was developed it made sense to not just to drop outliers because the resolution was low and every datapoint was valuable. With modern technologies the resolution is much higher and we can afford dropping such outliers, which can be done by: \begin{verbatim} <%=withCapture({ data <- dropSegmentationOutliers(data) })%> \end{verbatim} Dropping TCN outliers is optional. \section{Paired PSCBS segmentation} \subsection{Skipping centromeres and other large gaps} \label{secGaps} Like the CBS method, Paired PSCBS does not take the physical locations (in units of nucleotides) of the loci in to account when segmenting the data, only their relative ordering along the genome. This means that after having ordered the loci along genome, it will treat two "neighboring" loci that are on both sides of the centromere equally to two neighboring loci that are only a few hundred bases apart. This may introduce erroneous change points that appear to be inside the centromere. The same issues occur for other large gaps of the genome where there are no observed signals. To avoid this, although not mandatory, we will locate all gaps of the genome where there are no observed loci. As a threshold we will consider a region to be a "gap" if the distance between the two closest loci is greater than 1Mb. \begin{verbatim} <%=withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps })%> \end{verbatim} which shows that there is a 20.5Mb long gap between 121.0Mb and 141.5Mb on Chromosome~1. This is the centromere of Chromosome~1. It is not possible to specify "gaps" to the segmentation function. Instead they need to be given as part of a set of "known" segments, which is done as: \begin{verbatim} <%=withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments })%> \end{verbatim} Below, we will use this to tell Paired PSCBS to segment Chromosome~1 into three independent segments, where the first segment is from the beginning of the chromosome (hence '-Inf') to 120.1Mb, the second one from 120.1-141.5Mb (the above gap), and the third one is from 141.5Mb to the end of the chromosome (hence '+Inf'). Just as Paired PSCBS segments chromosomes independently of each other, it also segments priorly known segments independently of each other. Specifying known segments is optional. \subsection{Identifying PSCN segments} We are now ready to segment the locus-level PSCN signals. This is done by\footnote{We fix the random seed in order for the results of this vignette to be numerically reproducible.}: \begin{verbatim} <%=withCapture({ fit <- segmentByPairedPSCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) })%> \end{verbatim} Note that this may take several minutes when applied to whole-genome data. The above call will also normalize the tumor BAFs using the TumorBoost normalization method~\citep{BengtssonH_etal_2010} (without preserving the relative scale for homozygous and heterozygous BAFs; in a future version, this will be the default). If this has already been done or the tumor signals have been normalized by other means, the TumorBoost step can be skipped by setting argument \code{tbn=FALSE}. The result of the segmentation is a set of segments identified to have the same underlying PSCN levels. In this particular case, <%=nbrOfSegments(fit)%> PSCN segments were found: <% fit <- fixLocations(fit) %> \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> Note that Segment~\#<%=which(segs$tcnNbrOfLoci == 0)%> has no mean-level estimates. It is because it corresponds to the centromere (the gap) that was identified above. Paired PSCBS did indeed try to segment it, but since there are no data points, all estimates are missing values. Similarly, for Segment~\#<%=which(segs$dhNbrOfLoci == 0)%> the DH and minor and major CNs mean estimates are all missing values. This is because, Paired PSCBS identified that segment by first segmenting the TCN signals by themselves, and after which it tried to segment the DH signals within that segment. Since there are no heterozygous SNPs in the segment, there are no DH signals, and hence there is no DH mean estimate. \subsection{Displaying genomic PSCN profiles} To plot the PSCN segmentation results, do: \begin{verbatim} plotTracks(fit) \end{verbatim} which by default displays three panels containing TCN, decrease of heterozygosity (DH), and minor and major CNs as in Figure~\ref{figTracks}. To plot only one panel with TCN and minor and major CNs and zoom in on a particular region, do (not shown): \begin{verbatim} plotTracks(fit, tracks="tcn,c1,c2", xlim=c(120,244)*1e6) \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fit)[1L], "tracks"), aspectRatio=0.6, { plotTracks(fit) })%>}} \end{center} \caption{PSCN segments identified by Paired PSCBS. \textbf{Top}: The TCN signals with the TCN mean levels (purple). \textbf{Middle}: The DH signals with the DH mean levels (orange). \textbf{Bottom}: The TCN signals with the minor CN ($C_1$; blue), the major CN ($C_2$; red) and the TCN ($C=C_1+C_2$; purple) mean levels. } \label{figTracks} \end{figure} \section{Calling segments} The calling algorithms for allelic balance (AB) and loss of heterozygosity (LOH) are based on quantile estimates of the different mean levels. These estimates are obtained using non-parametric bootstrap techniques. For more details, see~\citet{OlshenA_etal_2011}. After the Paired PSCBS method was published, we have added methods for calling run of homozygosity (ROH) and neutral total copy number (NTCN). \emph{The ROH and NTCN calling methods should be considered under development until further notice, meaning they and their results may change without notice.} \subsection{Calling segments with run of homozygosity (ROH)*} \emph{Please note that this method is under development. This means that it may change without further notice.} A region has a run of homozygotes (ROH) if all of its SNPs are homozygous (in the normal). Since such a region has no heterozyous SNPs, its decrease in heterozygosity (DH) is undefined. Likewise, the minor and major copy numbers are unknown. However, if there are genotyping errors within an ROH region, we will obtain a non-missing DH mean level and hence also finite minor and major CNs. In order to adjust for these faulty estimates, we test if the identified segments are ROHs or not by: \begin{verbatim} <%=withCapture({ fit <- callROH(fit, verbose=-10) })%> \end{verbatim} This will also set the corresponding DH and minor and major CN mean levels to NA. The total CN mean levels are not affected by the ROH call. \subsubsection{Tuning parameters} For each segment, the test for ROH calculates the fraction of SNPs that are called heterozygous. If the fraction of heterozygotes is smaller than a threshold, the segmented is called ROH, otherwise not. The default threshold is 1/12. To use a different threshold, set argument \code{delta} to a scalar in $[0,1]$. For example, using \code{callROH(fit, delta=1/30)} makes the ROH caller more conservative.\footnote{It is our plan to replace this basic test with a bionomial test.} \subsection{Calling segments in allelic balance (AB)} The AB caller tests whether the DH level of a segment is small enough to be considered zero, which means that the minor and the major CNs are equal, i.e. the segment is in allelic balance. To call the AB state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callAB(fit, verbose=-10) })%> \end{verbatim} Because the caller utilizes bootstrapping techniques, calling AB may take some time if there is a large number of segments. Segments already called ROH will not be called for AB, and their AB statuses will have a missing value (\code{NA}). \subsubsection{Tuning parameters} The AB caller tests whether a segment's DH is zero or not, by comparing its DH level (or more precisely, the $5\%$ quantile of its bootstrapped DH mean level) to a threshold. This threshold will be a function of the noise level, because the noisier the BAF signals (and hence the DH signals), the greater the bias of the DH mean level for segments in AB will be. Because of this, the threshold is chosen from data by estimating the noise level of the DH signals near zero. Further rationales and details are given in~\citet{OlshenA_etal_2011}. The AB threshold can be estimated explicitly and used in the caller as \begin{verbatim} deltaAB <- estimateDeltaAB(fit, scale=1) fit <- callAB(fit, delta=deltaAB) \end{verbatim} By decreasing argument \code{scale} (a positive scalar), a smaller threshold will be obtained resulting in a more conservative AB caller. \subsection{Calling segments with loss of heterozygosity (LOH)} The LOH caller tests whether the minor CN level of a segment is large enough to be considered non-zero, which means that the segment is \emph{not} in LOH. To call the LOH state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callLOH(fit, verbose=-10) })%> \end{verbatim} Note that in order to call LOH, one has to call allelic balance first. Since the bootstrapping was already done in the AB caller, it is not repeated here, which is why calling LOH is faster than calling AB. Analogously to the AB caller, segments already called ROH will not be called for LOH, and their LOH statuses will have a missing value (\code{NA}). Segments already called AB will be called non-LOH, because AB and LOH are exclusively mutual states. \subsubsection{Tuning parameters} The LOH caller tests whether a segment's minor CN is non-zero or not, by comparing its minor CN level (or more precisely, the $95\%$ quantile of its bootstrapped minor CN mean level) to a threshold. This threshold will, among other components, be a function of normal contamination, i.e. the greater the fraction of normal cells is the greater the threshold needs to be in order to call LOH in the tumor cells. Because of this, the threshold is chosen from data as the midpoint of the estimated levels of minor CNs zero and one, which in turn is a function of the normal contamination. For details on the definition of LOH and details on the LOH caller, see~\citet{OlshenA_etal_2011}. The LOH threshold can be estimated explicitly and used as: \begin{verbatim} deltaLOH <- estimateDeltaLOH(fit, midpoint=1/2) fit <- callLOH(fit, delta=deltaLOH) \end{verbatim} By decreasing argument \code{midpoint} in $[0,1]$, a smaller threshold will be obtained resulting in a more conservative LOH caller. \subsection{Calling segments with neutral total copy number (NTCN)*} \emph{Please note that this method is under development. This means that it may change without further notice.} The neutral total copy number (NTCN) caller tests whether the total CN level of a segment is neutral (e.g. diploid) or not. To call the NTCN state of all segments, do: \begin{verbatim} <%=withCapture({ fit <- callNTCN(fit, verbose=-10) })%> \end{verbatim} \subsubsection{Tuning parameters} The NTCN caller identifies segments which TCN mean levels (or more precisely, which $95\%$ confidence intervals) are within a given "acceptance" region. This acceptance region is determined by the $95\%$ confidence interval of an initial set of AB segments identified to be copy neutral and then expanded by half a TCN unit length. The true length of half a total copy number unit is specified by the argument \code{delta} to \code{callNTCN()}. Its length should be a function of the overall background signals (which includes normal contamination and more), such that the width of the acceptance region becomes smaller when the background increases. The background signal (\code{kappa}) and \code{delta} can be estimated explicitly as: \begin{verbatim} kappa <- estimateKappa(fit) deltaCN <- estimateDeltaCN(fit, scale=1, kappa=kappa) fit <- callNTCN(fit, delta=deltaCN, verbose=-10) \end{verbatim} By decreasing the tuning parameter \code{scale} (a positive scalar), a smaller acceptance region will be obtained, which results in a more conservative CN caller. \subsection{Results from calling ROH, AB, LOH and NTCN} All calls are appended to the segmentation results as logical columns: \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> \section{Saving results} \subsection{Writing segments to a tab-delimited text file} To write the PSCN segmentation results to file, do: \begin{verbatim} pathname <- writeSegments(fit, name="MySample", simplify=TRUE) \end{verbatim} With \code{simplify=FALSE} (default) quantile estimates of the different mean levels will also be written, which roughly doubles the file size. \section{Experimental} In this section we illustrate some of the ongoing and future work that will be contained in the PSCBS package. Please be aware that these methods are very much under construction, possibly incomplete and in the worst case, even incorrect. \subsection{Less biased Decrease of Heterozygosity (DH) estimates} The DH mean levels of the segments are estimated as the sample mean of the DH signals within each segment. Since DH signals are by definition truncated at zero, the mean level estimates will always be greater than zero even if the true underlying DH is exactly zero. An additional bias is introduced because the distribution of the DH signals is skewed for small DHs, causing the sample mean estimate to be biased. A less biased estimate can be obtained by using the median estimator. To use the median estimator for DH mean levels, specify argument \code{avgDH="median"} to the \code{segmentByPairedPSCBS()} call. Because the DH mean levels will be less biased, the $(C_1,C_2)$ mean level estimates will also be less biased, e.g. they will be closer to each other for segments that are in allelic balance. \subsection{Pruning segmentation profile} By applying hierarchical clustering on the segment means, it is possible to prune the PSCN profile such that change points with very small absolute changes are dropped. If change points are dropped this way, this results in a smaller number of segments, which are hence longer on average. To prune Paired PSCBS segmentation results this way, do: \begin{verbatim} <%=withCapture({ fitP <- pruneByHClust(fit, h=0.25, verbose=-10) })%> \end{verbatim} The result of this is shown in Figure~\ref{figTracksPruned}. \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fitP)[1L], "pruned", "tracks"), aspectRatio=0.6, { plotTracks(fitP) })%>}} \end{center} \caption{Pruned PSCN segments plotted as in Figure~\ref{figTracks}.} \label{figTracksPruned} \end{figure} In the current implementation, any segment calls and quantile mean levels estimates previously are dropped when pruning. \subsection{Report generation} A multipage PDF report that contains both whole-genome and per-chromosome summaries and figures can be generated by: \begin{verbatim} > report(fit, sampleName="PairedPSCBS", studyName="PSCBS-Ex", verbose=-10) \end{verbatim} By default, the reports are written to directory \code{reports//} under the current working directory. In addition to the PDF, that directory also contains subdirectory \code{figures/} holding all generated figure files (e.g. PNGs and PDFs) for easy inclusion elsewhere. <%------------------------------------------------------------------- REFERENCES -------------------------------------------------------------------%> \bibliographystyle{natbib} \bibliography{PSCBS} <%------------------------------------------------------------------- APPENDIX -------------------------------------------------------------------%> \clearpage \section*{Appendix} \subsection*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using \code{rfile()} of the R.rsp package. Total processing time after RSP-to-R translation was <%=dt <- round(Sys.time()-t0, digits=2)%> <%=attr(dt, "units")%>. \end{document} PSCBS/inst/doc/PairedPSCBS.R0000644000176200001440000000456715000517067015005 0ustar liggesusers########################################################################### ### This 'tangle' R script was created from an RSP document. ### RSP source document: 'PairedPSCBS.tex.rsp' ### Metadata 'title': 'Parent-specific copy-number segmentation using Paired PSCBS' ### Metadata 'author': 'Henrik Bengtsson' ### Metadata 'engine': 'R.rsp::rsp' ### Metadata 'keywords': 'copy numbers, allele specific, parent specific, genomic aberrations' ########################################################################### t0 <- Sys.time() R.utils::use("R.utils") # RSP specific R.rsp <- R.oo::Package("R.rsp") withCapture <- R.utils::withCapture options("withCapture/newline"=FALSE) options(str=strOptions(strict.width="cut")) options(width=85) options(digits=3) # Graphics use("R.devices") options("devEval/args/field"="fullname") # Preferred for LaTeX devOptions("png", width=840) # Analysis use("PSCBS") PSCBS <- R.oo::Package("PSCBS") fixLocations <- function(fit, ...) { for (key in grep("(end|start)$", colnames(fit$output))) { fit$output[[key]] <- as.integer(fit$output[[key]]) } fit } # fixLocations() R.rsp$version R.rsp$author format(as.Date(PSCBS$date), format="%B %d, %Y") fullname <- "PairedPSCBS,exData,chr01" withCapture({ data <- PSCBS::exampleData("paired.chr01") str(data) }) withCapture({ data <- dropSegmentationOutliers(data) }) withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps }) withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments }) withCapture({ fit <- segmentByPairedPSCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) }) nbrOfSegments(fit) fit <- fixLocations(fit) withCapture({ getSegments(fit, simplify=TRUE) }) segs <- getSegments(fit, simplify=TRUE) which(segs$tcnNbrOfLoci == 0) which(segs$dhNbrOfLoci == 0) toPNG(fullname, tags=c(class(fit)[1L], "tracks"), aspectRatio=0.6, { plotTracks(fit) }) withCapture({ fit <- callROH(fit, verbose=-10) }) withCapture({ fit <- callAB(fit, verbose=-10) }) withCapture({ fit <- callLOH(fit, verbose=-10) }) withCapture({ fit <- callNTCN(fit, verbose=-10) }) withCapture({ getSegments(fit, simplify=TRUE) }) segs <- getSegments(fit, simplify=TRUE) withCapture({ fitP <- pruneByHClust(fit, h=0.25, verbose=-10) }) toPNG(fullname, tags=c(class(fitP)[1L], "pruned", "tracks"), aspectRatio=0.6, { plotTracks(fitP) }) toLatex(sessionInfo()) dt <- round(Sys.time()-t0, digits=2) attr(dt, "units") PSCBS/inst/doc/CBS.pdf0000644000176200001440000070535315000517040013755 0ustar liggesusers%PDF-1.5 %ÐÔÅØ 62 0 obj << /Length 979 /Filter /FlateDecode >> stream xÚ…UKoã6¾çWèH͇(‰½%iÓ,ߺ{ %ÆV#KEÅõ¿ïCoìÝ,šChÎ{¾3bÙ6cÙ¯7ìÎûõÍêQèŒ×TpUfë—Œ+Ie%³Jq*µÈÖ]ö7YçuC&o†¼Lv:ä¢&§¼à¤È9sQ‘eþoòþ[‡†³ÝîmÔzãûiDé2÷ã>Ü?ç_Ö¬%Ë8§Z)‹`5eÈ ÑÐFs,â7;ºþü 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function(fit, ...) { for (key in grep("(end|start)$", colnames(fit$output))) { fit$output[[key]] <- as.integer(fit$output[[key]]) } fit } # fixLocations() signalType <- "TCN" R.rsp$version R.rsp$author format(as.Date(PSCBS$date), format="%B %d, %Y") fullname <- "PairedPSCBS,exData,chr01" withCapture({ data <- PSCBS::exampleData("paired.chr01") data <- data[,c("chromosome", "x", "CT")] colnames(data)[3] <- "y" str(data) }) signalType signalType withCapture({ data <- dropSegmentationOutliers(data) }) signalType withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps }) withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments }) signalType signalType withCapture({ fit <- segmentByCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) }) signalType nbrOfSegments(fit) signalType fit <- fixLocations(fit) withCapture({ getSegments(fit, simplify=TRUE) }) segs <- getSegments(fit, simplify=TRUE) which(segs$nbrOfLoci == 0) signalType signalType signalType toPNG(fullname, 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options(str=strOptions(strict.width="cut")) options(width=85) options(digits=3) # Graphics use("R.devices") options("devEval/args/field"="fullname") # Preferred for LaTeX devOptions("png", width=840) # Analysis use("PSCBS") PSCBS <- R.oo::Package("PSCBS") fixLocations <- function(fit, ...) { for (key in grep("(end|start)$", colnames(fit$output))) { fit$output[[key]] <- as.integer(fit$output[[key]]) } fit } # fixLocations() signalType <- "TCN" %> \documentclass[letter]{article} \usepackage{xspace} \usepackage{alltt} \usepackage{xcolor} \usepackage{natbib} % \citep{}, \citet{} \usepackage{graphicx} \graphicspath{{figures/}} <%------------------------------------------------------------------- Assign PDF metadata -------------------------------------------------------------------%> % PDF metadata \usepackage{hyperref} % Ideally \hypersetup{hidelinks}, but for backward compatibility: \hypersetup{pdfborder={0 0 0}} \hypersetup{ pdfauthor={<%@meta name="author"%>}, pdftitle={<%@meta 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\date{<%=format(as.Date(PSCBS$date), format="%B %d, %Y")%>} \begin{document} \maketitle \begin{abstract} The Circular Binary Segmentation (CBS) method partitions a genome into segments of constant total copy numbers (TCNs) based on DNA microarray data. The method also calls .... CBS was designed to work with data from any DNA microarray technology and generation, including Affymetrix and Illumina. This document shows how to use the \pkg{PSCBS} package to run CBS on a tumor sample. \end{abstract} \keywords{<%@meta name="keywords"%>} \begin{center} \emph{This vignette is distributed as part of the \pkg{PSCBS} package, which is available on CRAN (\url{https://cran.r-project.org/}). The authors very much appreciate feedback on this document.} \end{center} \clearpage \tableofcontents \clearpage <%------------------------------------------------------------------- BACKGROUND -------------------------------------------------------------------%> \section{Background} \label{secBackground} We will here use a small example data set to illustrate how to setup the data in a format suitable for CBS, how to identify segments, how to call them, and how to plot and export the segmentation results. The statistical model and the algorithm behind CBS is explained in detail in \citet{OlshenA_etal_2004, VenkatramanOlshen_2007}. <%------------------------------------------------------------------- EXAMPLE -------------------------------------------------------------------%> \section{Preparing data to be segmented} The CBS method requires total copy-number (TCN) estimates. More precisely, it requires TCN ratios for a sample of interest relative to a reference ($y$). The genomic location of the loci in form of chromosome and physical position are also required. \subsection{Locus-level total copy-number signals} \label{secData} In this example we will use a small example data set part of the \pkg{PSCBS} package. It can be loaded as: <% fullname <- "PairedPSCBS,exData,chr01" %> \begin{verbatim} <%=withCapture({ data <- PSCBS::exampleData("paired.chr01") data <- data[,c("chromosome", "x", "CT")] colnames(data)[3] <- "y" str(data) })%> \end{verbatim} In additional to the mandatory fields (\code{chromosome}, \code{x}, and \code{C} this data set also contains .... The latter will not be used here. \subsection{Dropping <%=signalType%> outliers} \label{secTCNOutliers} There may be some outliers among the <%=signalType%>s. In CBS~\citep{OlshenA_etal_2004,VenkatramanOlshen_2007}, the authors propose a method for identifying outliers and then to shrink such values toward their neighbors ("smooth") before performing segmentation. At the time CBS was developed it made sense to not just to drop outliers because the resolution was low and every datapoint was valuable. With modern technologies the resolution is much higher and we can afford dropping such outliers, which can be done by: \begin{verbatim} <%=withCapture({ data <- dropSegmentationOutliers(data) })%> \end{verbatim} Dropping <%=signalType%> outliers is optional. \section{CBS segmentation} \subsection{Skipping centromeres and other large gaps} \label{secGaps} The CBS method does not take the physical locations (in units of nucleotides) of the loci in to account when segmenting the data, only their relative ordering along the genome. This means that after having ordered the loci along genome, it will treat two "neighboring" loci that are on both sides of the centromere equally as two neighboring loci that are only few hundred bases apart. This may introduce erroneous change points that appears to be inside the centromere and biological impossible interpretation of the identified copy-number states. The same issues occur for other large gaps of the genome where there are no observed signals. To avoid this, although not mandatory, we will locate all gaps of the genome where there are no observed loci. As a threshold we will consider a region to be a "gap" if the distance between the two closest loci is greater than 1Mb. \begin{verbatim} <%=withCapture({ gaps <- findLargeGaps(data, minLength=1e6) gaps })%> \end{verbatim} which shows that there is a 20.5Mb long gap between 121.0Mb and 141.5Mb on Chromosome~1. This is the centromere of Chromosome~1. Gaps cannot be specified directly. Instead they need to be give as part of a set of "known" segments, which is done as: \begin{verbatim} <%=withCapture({ knownSegments <- gapsToSegments(gaps) knownSegments })%> \end{verbatim} Below, we will use this to tell CBS to segment Chromosome~1 in three independent segments, where the first segments is from the beginning of the chromosomes (hence '-Inf') to 120.1Mb, the second from 120.1-141.5Mb (the above gap), and the third is from 141.5Mb to the end of the chromosome (hence '+Inf'). Just as CBS segments chromosomes independently of each other, it also segments priorly known segments independently of each other. Specifying known segments is optional. \subsection{Identifying <%=signalType%> segments} We are now ready to segment the locus-level <%=signalType%> signals. This is done by\footnote{We fix the random seed in order for the results of this vignette to be exactly reproducible.}: \begin{verbatim} <%=withCapture({ fit <- segmentByCBS(data, knownSegments=knownSegments, seed=0xBEEF, verbose=-10) })%> \end{verbatim} Note that this may take several minutes when applied to whole-genome data. The result of the segmentation is a set of segments identified to have the same underlying <%=signalType%> levels. In this particular case, <%=nbrOfSegments(fit)%> <%=signalType%> segments were found: <% fit <- fixLocations(fit) %> \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> Note how Segment~\#<%=which(segs$nbrOfLoci == 0)%> has no mean-level estimates. It is because it corresponds to the centromere (the gap) that was identified above. CBS did indeed try to segment it, but since there are no data points, all estimates are missing values. \subsection{Displaying genomic <%=signalType%> profiles} To plot the <%=signalType%> segmentation results, do: \begin{verbatim} plotTracks(fit) \end{verbatim} which displays <%=signalType%> as in Figure~\ref{figTracks}. To zoom in on a particular region, do: \begin{verbatim} plotTracks(fit, xlim=c(120,244)*1e6) \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fit)[1L], "tracks"), aspectRatio=0.35, { plotTracks(fit) })%>}} \end{center} \caption{Segments identified by CBS. The <%=signalType%> signals with the <%=signalType%> mean levels (purple). } \label{figTracks} \end{figure} \section{Calling segments} TBA. <%--- \subsection{Results from calling <%=signalType%> states} All calls are appended to the segmentation results as logical columns: \begin{verbatim} <%=withCapture({ getSegments(fit, simplify=TRUE) })%> \end{verbatim} <% segs <- getSegments(fit, simplify=TRUE) %> ---%> \section{Saving results} \subsection{Writing segments to a tab-delimited text file} To write the <%=signalType%> segmentation results to file, do: \begin{verbatim} pathname <- writeSegments(fit, name="MySample", simplify=TRUE) \end{verbatim} \section{Experimental} In this section we illustrate some of the ongoing and future work of the PSCBS package. Please be aware that these methods are very much under construction, possibly incomplete and in worst case even incorrect. \subsection{Pruning segmentation profile} By using hierarchical cluster of the segment means it is possible to prune the <%=signalType%> profile such that change points with very small absolute changes are dropped. If change points are dropped this way, this results in a smaller number of segments, which are hence longer. \begin{verbatim} <%=withCapture({ fitP <- pruneByHClust(fit, h=0.25, verbose=-10) })%> \end{verbatim} \begin{figure}[htp] \begin{center} \resizebox{0.96\textwidth}{!}{\includegraphics{<%=toPNG(fullname, tags=c(class(fitP)[1L], "pruned", "tracks"), aspectRatio=0.35, { plotTracks(fitP) })%>}} \end{center} \caption{Pruned <%=signalType%> segments plotted as in Figure~\ref{figTracks}.} \label{figTracksPruned} \end{figure} \subsection{Report generation} A multipage PDF report that contains both whole-genome and per-chromosome summaries and figures can be generated by: \begin{verbatim} > report(fit, sampleName="CBS", studyName="CBS-Ex", verbose=-10) \end{verbatim} By default, the reports are written to directory \code{reports//} under the current working directory. In addition to the PDF, that directory also contains subdirectory \code{figures/} holding all generated figure files (e.g. PNGs and PDFs) for easy inclusion elsewhere. <%------------------------------------------------------------------- REFERENCES -------------------------------------------------------------------%> \bibliographystyle{natbib} \bibliography{PSCBS} <%------------------------------------------------------------------- APPENDIX -------------------------------------------------------------------%> \clearpage \section*{Appendix} \subsection*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using \code{rfile()} of the R.rsp package. Total processing time after RSP-to-R translation was <%=dt <- round(Sys.time()-t0, digits=2)%> <%=attr(dt, "units")%>. \end{document} PSCBS/inst/templates/0000755000176200001440000000000014564051545014110 5ustar liggesusersPSCBS/inst/templates/rsp/0000755000176200001440000000000014564051545014714 5ustar liggesusersPSCBS/inst/templates/rsp/bioinformatics-journals-abbr.bib0000644000176200001440000000445714564051545023153 0ustar liggesusers@comment{DESCRIPTION:%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Usage: \bibliography{, } Example: \bibliography{bioinformatics-journals-full,hb-at-maths.lth.se} \bibliography{bioinformatics-journals-abbr,hb-at-maths.lth.se} Description: This bib-file should be included as a preamble for the main bib-file containing the actual references. Author: Henrik Bengtsson, Version: See end of file for document history. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % Journals % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - @STRING{AmStat = {Am. Stat.}} @STRING{AnnStat = {Ann. Statist.}} @STRING{AnalChem = {Anal. Chem.}} @STRING{ApplStat = {Appl. Statist.}} @STRING{Bioinformatics = {Bioinformatics}} @STRING{Biometrika = {Biometrika}} @STRING{BJMSP = {Br. J. Math. Stat. Psychol.}} @STRING{Blood = {Blood, Am Soc Hematol}} @STRING{BMCBioinfo = {BMC Bioinfo.}} @STRING{BMCBiotech = {BMC Biotech.}} @STRING{BMCGen = {BMC Genom.}} @STRING{CancerRes = {Cancer Res.}} @STRING{ExpCellRes = {Exp. Cell Res.}} @STRING{GenBio = {Genome Bio.}} @STRING{GenRes = {Genome Res.}} @STRING{JASA = {J. Am. Stat. Assoc.}} @STRING{JBioOpt = {J. Biomed. Optics}} @STRING{JCompBio = {J. Comput. Biol.}} @STRING{JCompGraphStat = {J. Comp. Graph. Stat.}} @STRING{JRSS = {J. Royal Stat. Soc.}} @STRING{JSPI = {J. Stat. Plan. Inf.}} @STRING{Microcirc = {Microcirc.}} @STRING{NAR = {Nucleic Acids Res.}} @STRING{NatBiotech = {Nature Biotechnol.}} @STRING{NatGen = {Nature Genet.}} @STRING{NatMed = {Nature Med.}} @STRING{NatMet = {Nature Met.}} @STRING{PNAS = {Proc. Natl. Acad. Sci. USA}} @STRING{SAGMB = {Stat. App. Gen. Mol. Bio.}} @STRING{Sankhya = {Sankhya}} @STRING{StatInf = {Stat. Inf.}} @STRING{StatSci = {Stat. Sci.}} @STRING{StatSin = {Stat. Sin.}} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % Institutions % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - @STRING{MatStatLU = {Centre for Math. Sci., Lund Univ.}} @comment{HISTORY:%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% o 2004-12-07 Created. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%} PSCBS/inst/templates/rsp/NonPairedPSCBS,report.tex.rsp0000644000176200001440000002152614564051545022231 0ustar liggesusers<%-------------------------------------------------------------------- This is an RSP LaTeX template for the report system of PSCBS. --------------------------------------------------------------------%> <%@meta author="Henrik Bengtsson"%> <%@meta date="2013-03-21"%> <%-------------------------------------------------------------------- Include RSP templates --------------------------------------------------------------------%> <%@include file="includes/reportHeader.tex.rsp"%> <% library("PSCBS"); library("R.devices"); library("R.cache"); getChecksum <- R.cache::getChecksum; stopifnot(exists("rspArgs", mode="list")); %> <%-------------------------------------------------------------------- Report configuration --------------------------------------------------------------------%> <%@logical SIGNAL_DENSITIES="${PSCBS::reports/signalDensities}" default="TRUE"%> <%@logical LEVEL_DENSITIES="${PSCBS::reports/levelDensities}" default="TRUE"%> <%@logical C1C2="${PSCBS::reports/pscnSegmentationTransitions}" default="FALSE"%> <%-- To implement --%> <%@logical PER_GENOTYPE="${PSCBS::reports/perGenotype}" default="TRUE"%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % LATEX STARTUP %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \documentclass[twoside,12pt]{article} \usepackage{fancyvrb} % Custom verbose environments \usepackage{lastpage} % Total number of pages \usepackage{xspace} \usepackage{subfigure} % \subfigure[]{} \usepackage[round]{natbib} % No paragraph indentation \setlength{\parindent}{0cm} \addtolength{\oddsidemargin}{-0.4in} \addtolength{\evensidemargin}{-1.02in} \addtolength{\textwidth}{1.5in} \addtolength{\topmargin}{-1.0in} \addtolength{\textheight}{1.5in} \renewcommand{\topfraction}{1.00} % max fraction of floats at top \renewcommand{\bottomfraction}{1.0} % max fraction of floats at bottom \renewcommand{\textfraction}{0.00} <%@include file="includes/reportSetupGraphics.tex.rsp"%> <%@include file="includes/reportSetupMacros.tex.rsp"%> <% pairedPSCBSReport <- function(fit, sampleName=sampleName(fit), dataSet=NULL, studyName=NULL, chromosomes=NULL, Clim=c(0,4), Blim=c(0,1), reportPerChromosome=TRUE, ...) { %> <%@if name="SIGNAL_DENSITIES"%> <%@include file="includes/signalDensities.tex.rsp"%> <%@endif%> <%@include file="includes/summaryOfAnnotationAndGenotypeCalls.tex.rsp"%> <%@include file="includes/pscnSegmentationTracks.tex.rsp"%> <%@if name="LEVEL_DENSITIES"%> <%@include file="includes/levelDensities.tex.rsp"%> <%@endif%> <%@include file="includes/pscnSegmentationTransitions.tex.rsp"%> <% # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': fit <- Arguments$getInstanceOf(fit, "PairedPSCBS"); fitClass <- class(fit)[1L]; if (inherits(fit, "NonPairedPSCBS")) { fitClassLbl <- "Non-paired PSCBS"; } else if (inherits(fit, "PairedPSCBS")) { fitClassLbl <- "Paired PSCBS"; } else if (inherits(fit, "CBS")) { fitClassLbl <- "CBS"; } else { fitClassLbl <- fitClass; } # Argument 'sampleName': stopifnot(is.character(sampleName)); sampleName <- Arguments$getCharacter(sampleName); sampleNameEscDots <- gsub(".", "_", sampleName, fixed=TRUE); # Argument 'dataSet': if (!is.null(dataSet)) { dataSet <- Arguments$getCharacter(dataSet); } else { dataSet <- "?"; } dataSetLbl <- sprintf("Data set: %s\\\\", toLatex(dataSet)); # Argument 'studyName': if (is.null(studyName)) studyName <- fitClassLbl; studyName <- Arguments$getCharacter(studyName); studyLbl <- sprintf("Study: %s\\\\", toLatex(studyName)); # Argument 'chromosomes': if (!is.null(chromosomes)) { fit <- extractChromosomes(fit, chromosomes); } %> <%reportHeaderSetup(fit, sampleName=sampleName, dataSet=dataSet, studyName=studyName) %> <%reportHeaderUpdate(fit)%> <% ClimX <- Clim + c(-1,1)*diff(Clim)*0.08; BlimX <- Blim + c(-1,1)*diff(Blim)*0.08; %> \begin{document} \title{<%=fitClassLbl%> Report:\\<%=studyLbl%><%=dataSetLbl%>Sample: <%=toLatex(sampleName)%>} \author{Report template by <%@meta name="author"%>} \maketitle \thispagestyle{fancy} %%\tableofcontents %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % DATA %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % METHODS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Introduction} \label{sec:Introduction} This is a quality control (QC) report based on non-paired tumor SNP microarray data. \subsection{Method} \label{sec:Method} We use a non-paired PSCBS segmentation method to partion the genome into segments such that all signals in a particular segment are likely to originate from the same underlying parent-specific copy-number state. This method is adopted from the Paired PSCBS segmentation method~\citep{OlshenA_etal_2011} with two main differences. First, heterozygous SNPs are "called" based on tumor allele B fractions ("tumor BAFs"), which are poor proxies for the corresponding normal ones. This is a major disadvantage compared to having a matched normal. Second, the tumor BAFs cannot be normalized using the TumorBoost method~\citep{BengtssonH_etal_2010}. <%-- \subsection{Post-segmentation pruning} \label{sec:PostSegmentationPruning} <% fitP <- pruneByHClust(fit, h=0.25); #print(fitP); %> --%> \clearpage %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % RESULTS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % WHOLE-GENOME RESULTS % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \section{Whole-Genome Results} \label{ch:WholeGenomeResults} <%=summaryOfAnnotationAndGenotypeCalls(fit)%> <%@if name="SIGNAL_DENSITIES"%> <%=signalDensities(fit, fields=c("CT", "betaT", "rho", "c1", "c2"))%> <%@endif%> <%=pscnSegmentationTracks(fit)%> <%@if name="LEVEL_DENSITIES"%> <%=levelDensities(fit, fields=c("tcn", "dh", "c1", "c2"))%> <%@endif%> <%@if name="C1C2"%> <%=pscnSegmentationTransitions(fit)%> <%@endif%> % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = <% if (reportPerChromosome && nbrOfChromosomes(fit) > 1) { %> <% for (chr in getChromosomes(fit)) { %> <% fitT <- extractChromosome(fit, chromosome=chr); %> \clearpage \section{Chromosome <%=chr%>} \label{sec:Chromosome<%=chr%>Results} <%reportHeaderUpdate(fit)%> <%=summaryOfAnnotationAndGenotypeCalls(fitT)%> <%@if name="SIGNAL_DENSITIES"%> <%=signalDensities(fitT, fields=c("CT", "betaT", "rho", "c1", "c2"))%> <%@endif%> <%=pscnSegmentationTracks(fitT)%> <%--- <%@if name="LEVEL_DENSITIES"%> <%=levelDensities(fitT, fields=c("tcn", "dh", "c1", "c2"))%> <%@endif%> ---%> <%@if name="C1C2"%> <%=pscnSegmentationTransitions(fitT)%> <%@endif%> <% } # for (chr ...) %> <% } # if (reportPerChromosome && nbrOfChromosomes(fit) > 1) %> <%-- % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: WHOLE-GENOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \subsection{Hierarchical pruning} \label{sec:HierarchicalPruning} % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = --%> \clearpage %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % REFERENCES %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% <%@include file="includes/references.tex.rsp"%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % APPENDIX %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \appendix \section{Appendix} <%@include file="includes/sessionInfo.tex.rsp"%> \end{document} <% } # pairedPSCBSReport() %> <%--- <% message(paste(capture.output({ str(rspArgs) }), collapse="\n")); message(paste(capture.output({ ll() }), collapse="\n")); %> ---%> <%=do.call("pairedPSCBSReport", args=rspArgs)%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % HISTORY: # 2012-11-03 # o Replaced deprecated ggplot2 functions. # 2012-09-16 # o Added easy report configuration at the very top. # 2012-05-30 # o Removed ggplot2 warnings on missing values. # 2012-02-28 # o Now it is possible to turn off usage of the alpha channel in # plots, e.g. setOption("PSCBS::report/useAlphaChannel", FALSE). # This is useful for if the alpha channel is not supported. % 2012-02-27 % o First successful run with real data. % o Now all of the report uses a PairedPSCBS object. % o Now making more use of templates. % o Now passing a data frame to segmentByPairedCBS(). % 2011-09-30 % o Created. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/������������������������������������������������������������������0000755�0001762�0000144�00000000000�14564051545�016522� 5����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/reportHeader.tex.rsp����������������������������������������������0000644�0001762�0000144�00000005705�14564051545�022502� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== REPORT HEADER ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> <%--------------------------------------------------------------------- Usage: Add reportHeaderSetup(fit) to the LaTeX preamble ---------------------------------------------------------------------%> <% reportHeaderSetup <- function(fit, sampleName=sampleName(fit), studyName, dataSet, ...) { %> <% getChecksum <- R.cache::getChecksum; fitClass <- class(fit)[1L]; sampleName <- Arguments$getCharacter(sampleName); sampleNameEscDots <- gsub(".", "_", sampleName, fixed=TRUE); %> % Header contain project and sample metadata \usepackage{fancyhdr} \setlength{\headheight}{40pt} \pagestyle{fancy}{\fancyhf{}} % Custom header (specified below) \renewcommand{\headrulewidth}{0pt} % Drop horizontal ruler \fancyfoot{} % clear all footer fields \newcommand{\chrLabel}[1]{WG\xspace} \fancyhead[C]{% \small \raggedright %% \textbf{Study:Dataset:Sample}: <%=toLatex(studyName)%>:<%=toLatex(dataSet)%>:<%=toLatex(sampleName)%>:\chrLabel \hfill \thepage/\pageref{LastPage}\\ %% \textbf{Compiled} & <%=Sys.Date()%> \centering \resizebox{\headwidth}{!}{\includegraphics{<%= tags <- c("wg", fitClass, "tcn,c1,c2", getChecksum(fit)); toPNG(name=sampleNameEscDots, tags=tags, width=1024, aspectRatio=0.07, { par(oma=c(0,0,0,0), mar=c(0,0,0,0)); plotTracks(fit, tracks="tcn,c1,c2", scatter=NULL, calls=NULL, callTresholds=FALSE, lwd=5, Clim=c(0,4), xlab="", ylab="", subplots=FALSE); })%>}}% %% \vspace{0.2ex} %% \hline } <% } # reportHeaderSetup() %> <%--------------------------------------------------------------------- Usage: Add reportHeaderUpdate(fit) whenever subsetting 'fit' ---------------------------------------------------------------------%> <% reportHeaderUpdate <- function(fit, ...) { %> <% chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \renewcommand{\chrLabel}{<%=chrsTags%>} <% } # reportHeaderUpdate() %> <%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== HISTORY: 2012-11-03 o Replaced deprecated ggplot2 functions. 2012-09-16 o Added easy report configuration at the very top. 2012-05-30 o Removed ggplot2 warnings on missing values. 2012-02-28 o Now it is possible to turn off usage of the alpha channel in plots, e.g. setOption("PSCBS::report/useAlphaChannel", FALSE). This is useful for if the alpha channel is not supported. 2012-02-27 o First successful run with real data. o Now all of the report uses a PairedPSCBS object. o Now making more use of templates. o Now passing a data frame to segmentByPairedCBS(). 2011-09-30 o Created. ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> �����������������������������������������������������������PSCBS/inst/templates/rsp/includes/sessionInfo.tex.rsp�����������������������������������������������0000644�0001762�0000144�00000000652�14564051545�022351� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== SESSION INFORMATION ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> \section*{Session information} <%=paste(toLatex(sessionInfo()), collapse="\n")%> This report was generated via \code{report(fit)} which utilizes the R.rsp package. The template for this report was created by Henrik Bengtsson and last updated on March 21, 2013. ��������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/summaryOfAnnotationAndGenotypeCalls.tex.rsp�����������������������0000644�0001762�0000144�00000003405�14564051545�027203� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SUMMARY ANNOTATION AND GENOTYPE CALLS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% summaryOfAnnotationAndGenotypeCalls <- function(fit, ...) { %> \subsection{Summary of annotation and genotype calls} <% data <- getLocusData(fit, fields="full"); nbrOfLoci <- nrow(data); nbrOfSNPs <- sum(data$isSNP, na.rm=TRUE); nbrOfHets <- sum(data$isHet, na.rm=TRUE); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> <% reportHeaderUpdate(fit) %> \begin{table}[htbp] \begin{center} \begin{tabular}{lrr} Description & Count & Fraction \\ \hline Number of loci & <%=nbrOfLoci%> & 100.00\% \\ Number of SNPs & <%=nbrOfSNPs%> & <%=sprintf("%.2f", 100*nbrOfSNPs/nbrOfLoci)%>\% \\ Number of heterozygous SNPs* & <%=nbrOfHets%> & <%=sprintf("%.2f", 100*nbrOfHets/nbrOfSNPs)%>\% \\ Number of non-polymorphic loci & <%=nbrOfLoci-nbrOfSNPs%> & <%=sprintf("%.2f", 100*(1-nbrOfSNPs/nbrOfLoci))%>\% \\ Number of chromosomes & <%=nbrOfChromosomes%> & - \\ \end{tabular} \caption{ Summary of the locus-level data on <%=chromosomesH%>. A locus is considered to be a SNP if it has either a non-missing BAF for the tumor. (*) Heterozygous calls are based on (whole-genome) naive calling by thresholding \emph{tumor} DHs. } \label{tbl:LocusStats} \end{center} \end{table} <% } # summaryOfAnnotationAndGenotypeCalls() %> �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/references.tex.rsp������������������������������������������������0000644�0001762�0000144�00000000404�14564051545�022166� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== REFERENCES ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> \bibliography{bioinformatics-journals-abbr,PSCBS} %\bibliographystyle{plain} \bibliographystyle{natbib} ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/pscnSegmentationTracks.tex.rsp������������������������������������0000644�0001762�0000144�00000003312�14564051545�024537� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % PARENT-SPECIFIC COPY-NUMBER SEGMENTATION TRACKS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% pscnSegmentationTracks <- function(fit, ...) { %> \clearpage \subsection{Parent-specific copy-number segmentation tracks} \label{sec:PSCNSegmentationTracks} <% chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} <% for (track in c("tcn", "dh", "tcn,c1,c2")) { %> <%-- <% for (track in c("tcn*", "betaT", "betaTN*", "dh*", "tcn*,c1*,c2-*")) { %> --%> \resizebox{\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, fitClass, gsub("[*-]", "", track), getChecksum(fit)); toPNG(name=sampleNameEscDots, tags=tags, width=1024, aspectRatio=0.25, { par(mar=c(1.3,4,0.7,1.2)+0.1, cex=1.5); plotTracksManyChromosomes(fit, tracks=track, knownSegment=TRUE, Clim=Clim); }); }%>}% }% \\ <% } # for (track ...) %> \end{center} \caption{ Results of <%=fitClassLbl%> segmentation on <%=chromosomesH%> projected onto TCN (top), DH (middle), as well as TCN, $C_1$ and $C_2$ (bottom). PSCBS segmentation is always done on TCN and DH data. There are in total $S=<%=nbrOfSegments(fit, splitters=FALSE)%>$ segments. } \label{fig:PairedPSCBS} \end{figure} <% } # pscnSegmentationTracks() %> ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/reportSetupGraphics.tex.rsp���������������������������������������0000644�0001762�0000144�00000004057�14564051545�024072� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== GRAPHICS SETTINGS ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> <%-------------------------------------------------------------------- Where to save images files --------------------------------------------------------------------%> \usepackage{graphicx} <% setOption <- R.utils::setOption; # Don't assume 'R.utils' is attached. figPath <- getOption("devEval/args/path", "figures/"); oFigPath <- setOption("devEval/args/path", figPath); on.exit({ setOption("devEval/args/path", oFigPath); }, add=TRUE); oPar <- setOption("devNew/args/par", list(lwd=2)); on.exit({ setOption("devNew/args/par", oPar); }, add=TRUE); %> % Figure paths \graphicspath{{<%=figPath%>/} {../<%=figPath%>/}} <%-------------------------------------------------------------------- Required packages --------------------------------------------------------------------%> <% require("ggplot2") || throw("Package not loaded: ggplot2"); %> <%-------------------------------------------------------------------- Color schemes --------------------------------------------------------------------%> <% muNCols <- c("#999999", "#000000", "#999999"); # ggplot2 options xnbrOpts <- element_text(colour="grey50", size=20, hjust=1, lineheight=0.9); ynbrOpts <- element_text(colour="grey50", size=20, vjust=1, lineheight=0.9); xlabOpts <- element_text(colour="black", size=28, hjust=0.5); ylabOpts <- element_text(colour="black", size=28, vjust=0.5, angle=90); %> <%-------------------------------------------------------------------- Figure label schemes --------------------------------------------------------------------%> <% labList <- list( CT = expression(C[T]), betaN = expression(beta[N]), betaT = expression(beta[T]), betaTN = expression(tilde(beta)[T]), rho = expression(rho), rhoN = expression(tilde(rho)), c1 = expression(C[1]), c2 = expression(C[2]), c1N = expression(tilde(C)[1]), c2N = expression(tilde(C)[2]) ); %> ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/reportSetupMacros.tex.rsp�����������������������������������������0000644�0001762�0000144�00000002315�14564051545�023551� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<%--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--== LATEX SETTINGS ==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--==--%> <%-------------------------------------------------------------------- LaTeX commands --------------------------------------------------------------------%> \newcommand{\code}[1]{\texttt{#1}\xspace} <%-------------------------------------------------------------------- LaTeX acronyms --------------------------------------------------------------------%> \newcommand{\TCN}{TCN\xspace} \newcommand{\BAF}{\BAF\xspace} \newcommand{\BAFN}{BAF$_{N}$\xspace} \newcommand{\BAFT}{BAF$_{T}$\xspace} \newcommand{\BAFTN}{BAF$^*_{T}$\xspace} <%-------------------------------------------------------------------- R-to-LaTeX symbols --------------------------------------------------------------------%> <% symbolList <- list( CT = "$C_{T}$", tcn = "$\\bar{C_{T}}$", betaN = "$\\beta_{N}$", betaT = "$\\beta_{T}$", betaTN = "$\\tilde{\\beta}_{T}$", dh = "$\\bar{\\rho}$", rho = "$\\rho$", rhoN = "$\\tilde{\\rho}$", c1 = "$C_{1}$", c2 = "$C_{2}$", c1N = "$\\tilde{C}_{1}$", c2N = "$\\tilde{C}_{2}$" ); %> �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/pscnSegmentationTransitions.tex.rsp�������������������������������0000644�0001762�0000144�00000003533�14564051545�025632� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % PARENT-SPECIFIC COPY-NUMBER TRANSITIONS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% pscnSegmentationTransitions <- function(fit, ...) { %> \clearpage \subsection{Parent-specific copy-number transitions} \label{sec:PSCNSegmentationTransitions} <% # plotC1C2Grid() require("aroma.cn") || throw("Package not loaded: aroma.cn"); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} \resizebox{0.6\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, fitClass, "C1C2", getChecksum(fit)); toPNG(name=sampleNameEscDots, tags=tags, width=640, aspectRatio=1, par=list(mar=c(4,4,1,1)+0.1, cex=2), { plotC1C2Grid(fit, Clim=ClimX); linesC1C2(fit, lwd=2); }, force=FALSE); }%>}% }% \end{center} \caption{ A graph representation of the minor ($C_1$) and major ($C_2$) copy-number segmentation on <%=chromosomesH%>, where the nodes represent ($S=<%=nbrOfSegments(fit, splitters=FALSE)%>$) segments and the lines change points. The size of a node reflects the length of the corresponding segment. The marginal distributions (gray curves) of the minor and the major CNs are projected onto the horizontal and vertical axis, respectively. To easy a visual comparison, the latter is also projected onto the horizontal axis (light blue curve). } \label{fig:C1C2} \end{figure} <% } # pscnSegmentationTransitions() %> ���������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/levelDensities.tex.rsp��������������������������������������������0000644�0001762�0000144�00000006632�14564051545�023035� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % LEVEL DENSITIES % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% levelDensities <- function(fit, fields=c("tcn", "dh", "c1", "c2"), ...) { %> <% # Argument 'fields': fields <- match.arg(fields, several.ok=TRUE); %> \clearpage \section{Level densities} \label{sec:LevelDensities} <% require("ggplot2") || throw("Package not loaded: ggplot2"); data <- getSegments(fit); unknown <- setdiff(fields, gsub("Mean$", "", names(data))); if (length(unknown) > 0L) { throw("Unknown locus data fields: ", paste(sQuote(unknown), collapse=", ")); } w <- sqrt(data$dhNbrOfLoci) w <- w / sum(w, na.rm=TRUE); data <- cbind(data, weight=w); params <- fit$params; chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} <% for (ff in fields) { %> <% symbol <- symbolList[[ff]]; panelTitle <- switch(ff, tcn="\\TCN", "NNN"); lim <- switch(ff, tcn=ClimX, CT=ClimX, c1=ClimX, c2=ClimX, c1N=ClimX, c2N=ClimX, BlimX); column <- sprintf("%sMean", ff); %> \raisebox{4ex}{<%=symbol%>} <% tags <- c(chrsTags, "segments", ff); %> \resizebox{0.33\textwidth}{!}{% \includegraphics{<%={ toPNG(name=sampleNameEscDots, tags=tags, width=640, aspectRatio=0.3, { #### gg <- ggplot(dataT, aes_string(x=column, weights="weight", y="..count..")); gg <- ggplot(data, aes_string(x=column, weight="weight", y="..count..")); h <- NULL; if (ff == "tcn") { h <- params$ntcnRange; ## label <- expression(%+-%*Delta[CN]); col <- "purple"; } else if (ff == "dh") { h <- params$deltaAB; label <- expression(Delta[AB]); col <- "orange"; } else if (ff == "c1") { h <- params$deltaLowC1; label <- expression(Delta[LOH]); col <- "blue"; } if (!is.null(h)) { gg <- gg + geom_vline(xintercept=h, colour=col, size=1.5); } # See https://github.com/hadley/ggplot2/wiki/Legend-Attributes gg <- gg + theme(legend.position=c(0.97, 0.75), legend.justification = 1, legend.direction="vertical", legend.title=element_text(size=0), legend.text=element_text(size=16)); gg <- gg + geom_density(size=2, na.rm=TRUE); gg <- gg + xlab(NULL); gg <- gg + ylab(NULL); gg <- gg + xlim(lim); gg <- gg + theme(axis.text.x=xnbrOpts, axis.text.y=ynbrOpts); gg <- gg + theme(axis.title.x=xlabOpts, axis.title.y=ylabOpts); suppressWarnings({ print(gg); }); }) # toPNG() }%>}% }% \\ % <% } # for (ff ...) %> \end{center} \caption{ Density estimates of (weighted) \emph{segment-level} signals on <%=chromosomesH%> where weights are proportional to the square-root of the number of heterozygous SNPs in each segment. } \label{fig:LevelDensity} \end{figure} <% } # levelDensities() %> ������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/includes/signalDensities.tex.rsp�������������������������������������������0000644�0001762�0000144�00000007711�14564051545�023202� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SIGNAL DENSITIES % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% signalDensities <- function(fit, fields=c("CT", "betaN", "betaT", "rho", "c1", "c2", "betaTN", "rhoN", "c1N", "c2N"), ...) { %> <% # Argument 'fields': fields <- match.arg(fields, several.ok=TRUE); %> \clearpage \section{Signal densities} \label{sec:SignalDensities} <% require("ggplot2") || throw("Package not loaded: ggplot2"); data <- getLocusData(fit, fields="full"); unknown <- setdiff(fields, names(data)); if (length(unknown) > 0L) { throw("Unknown locus data fields: ", paste(sQuote(unknown), collapse=", ")); } params <- fit$params; chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> <% if (nrow(data) >= 2L) { %> \begin{figure}[htbp] \begin{center} <% for (ff in fields) { %> <% symbol <- symbolList[[ff]]; panelTitle <- switch(ff, CT="\\TCN", betaN="\\BAFN", betaT="\\BAFT", betaTN="\\BAFTN", "NNN"); lim <- switch(ff, CT=ClimX, c1=ClimX, c2=ClimX, c1N=ClimX, c2N=ClimX, BlimX); %> \raisebox{4ex}{<%=symbol%>} <% for (by in c("all", "muN")) { %> <% tags <- c(chrsTags, by, ff); %> \resizebox{0.33\textwidth}{!}{% \includegraphics{<%={ toPNG(name=sampleNameEscDots, tags=tags, width=640, aspectRatio=0.3, { gg <- ggplot(data, aes_string(x=ff, y="..count..")); if (by == "all") { if (ff == "CT" && any(!data$isSNP, na.rm=TRUE)) { gg <- gg + aes(group=type, colour=type); } h <- NULL; if (ff == "rho") { h <- params$deltaAB; label <- expression(Delta[AB]); col <- "orange"; } else if (ff == "c1") { h <- params$deltaLowC1; label <- expression(Delta[LOH]); col <- "blue"; } if (!is.null(h)) { gg <- gg + geom_vline(xintercept=h, colour=col, size=1.5); } } else if (by == "muN") { gg <- gg + aes_string(group="muNx", colour="muNx"); gg <- gg + scale_color_manual(values=muNCols); } # See https://github.com/hadley/ggplot2/wiki/Legend-Attributes gg <- gg + theme(legend.position=c(0.97, 0.75), legend.justification = 1, legend.direction="vertical", legend.title=element_text(size=0), legend.text=element_text(size=16)); gg <- gg + geom_density(size=2, na.rm=TRUE); gg <- gg + xlab(NULL); gg <- gg + ylab(NULL); gg <- gg + xlim(lim); gg <- gg + theme(axis.text.x=xnbrOpts, axis.text.y=ynbrOpts); gg <- gg + theme(axis.title.x=xlabOpts, axis.title.y=ylabOpts); suppressWarnings({ print(gg); }); }, force=FALSE); }%>}% }% <% } # for (by ...) %> \\ % <% } # for (ff ...) %> \end{center} \caption{ Density estimates of \emph{locus-level} signals on <%=chromosomesH%> with and without TumorBoost normalization. The signals in the left and right panels are without and with stratification on genotype calls (AA and BB in gray and AB in black). If there are no allelic imbalances in the tumor, then the density of the tumor should be similar to a normal sample, that is, three bands of signals corresponding to the three genotype groups. } \label{fig:SignalDensity} \end{figure} <% } else { %> NOTE: No density plots produced for <%= chromosomesH %> because there are fewer than two loci. <% } ## if (nrow(data) >= 2L) %> <% } # signalDensities() %> �������������������������������������������������������PSCBS/inst/templates/rsp/PairedPSCBS,report.tex.rsp�������������������������������������������������0000644�0001762�0000144�00000056710�14564051545�021561� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Authors: Henrik Bengtsson % Created on: 2011-09-30 % Last updated: See HISTORY below. % % Usage: (compiles *.tex.rsp => tex.rsp.R => *.tex => *.dvi) % R.rsp::rsp("PairedPSCBS.tex.rsp", path="reports,rsp/"); %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% <% library("PSCBS"); library("R.devices"); library("R.cache"); library("R.utils"); # setOption() stopifnot(exists("rspArgs", mode="list")); %> <% # = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = # REPORT CONFIGURATION # = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = REPORT_DENSITIES <- getOption("PSCBS::reports/densities", TRUE); REPORT_TUMORBOOST <- getOption("PSCBS::reports/TumorBoost", TRUE); REPORT_USE_ALPHA_CHANNEL <- getOption("PSCBS::report/useAlphaChannel", TRUE); REPORT_PER_CHROMOSOME <- getOption("PSCBS::reports/perChromosome", TRUE); REPORT_C1C2 <- getOption("PSCBS::reports/pscnSegmentationTransitions", FALSE); # To implement: REPORT_PER_GENOTYPE <- getOption("PSCBS::reports/perGenotype", TRUE); %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % LATEX STARTUP %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \documentclass[twoside,12pt]{report} \usepackage{fancyvrb} \usepackage{xspace} \usepackage{subfigure} % \subfigure[<title>]{} \usepackage[round]{natbib} \addtolength{\oddsidemargin}{-0.5in} \addtolength{\evensidemargin}{-0.5in} \addtolength{\textwidth}{1in} \addtolength{\topmargin}{-0.8in} \addtolength{\textheight}{1.3in} \renewcommand{\topfraction}{1.00} % max fraction of floats at top \renewcommand{\bottomfraction}{1.0} % max fraction of floats at bottom \renewcommand{\textfraction}{0.00} \usepackage{fancyhdr} \pagestyle{fancy} %% \fancyhead{} % clear all header fields %% \fancyfoot{} % clear all footer fields %% \fancyhead[LE,RO]{\slshape \rightmark} %% \fancyfoot[C]{\thepage} \fancyhf{} \fancyhead[LE,RO]{\thepage} \fancyhead[RE]{\textit{\nouppercase{\leftmark}}} \fancyhead[LO]{\textit{\nouppercase{\rightmark}}} \newcommand{\code}[1]{\texttt{#1}\xspace} \newcommand{\TCN}{TCN\xspace} \newcommand{\BAF}{\BAF\xspace} \newcommand{\BAFN}{BAF$_{N}$\xspace} \newcommand{\BAFT}{BAF$_{T}$\xspace} \newcommand{\BAFTN}{BAF$^*_{T}$\xspace} <% pairedPSCBSReport <- function(fit, sampleName=NULL, dataSet=NULL, studyName="PairedPSCBS", Clim=c(0,4), Blim=c(0,1), reportPath=file.path("reports", studyName), figPath=file.path(reportPath, "figures"), ..., figForce=FALSE) { %> <% # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': fit <- Arguments$getInstanceOf(fit, "PairedPSCBS"); # Argument 'sampleName': if (is.null(sampleName)) { sampleName <- sampleName(fit); } sampleName <- Arguments$getCharacter(sampleName); # Argument 'dataSet': if (!is.null(dataSet)) { dataSet <- Arguments$getCharacter(dataSet); } # Argument 'studyName': studyName <- Arguments$getCharacter(studyName); # Argument 'reportPath': reportPath <- Arguments$getWritablePath(reportPath); # Argument 'figPath': figPath <- Arguments$getWritablePath(figPath); # Argument 'figForce': figForce <- Arguments$getLogical(figForce); %> <% oFigPath <- setOption("devEval/args/path", figPath); on.exit({ setOption("devEval/args/path", oFigPath); }, add=TRUE); oPar <- setOption("devNew/args/par", list(lwd=2)); on.exit({ setOption("devNew/args/par", oPar); }, add=TRUE); %> <% studyLbl <- sprintf("Study: %s\\\\", toLatex(studyName)); if (!is.null(dataSet)) { dataSetLbl <- sprintf("Data set: %s\\\\", toLatex(dataSet)); } else { dataSetLbl <- ""; } %> \title{Paired PSCBS Report:\\<%=studyLbl%><%=dataSetLbl%>Sample: <%=toLatex(sampleName)%>} \author{Report template by Henrik Bengtsson} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % GRAPHICS SETTINGS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% setOption("devEval/args/force", figForce); %> \usepackage{graphicx} \graphicspath{{<%=figPath%>/} {../<%=figPath%>/}} <% # GGPLOT2 SETTINGS ClimX <- Clim + c(-1,1)*diff(Clim)*0.08; BlimX <- Blim + c(-1,1)*diff(Blim)*0.08; muNCols <- c("#999999", "#000000", "#999999"); require("ggplot2") || throw("Package not loaded: ggplot2"); xnbrOpts <- element_text(colour="grey50", size=20, hjust=1, lineheight=0.9); ynbrOpts <- element_text(colour="grey50", size=20, vjust=1, lineheight=0.9); xlabOpts <- element_text(colour="black", size=28, hjust=0.5); ylabOpts <- element_text(colour="black", size=28, vjust=0.5, angle=90); labList <- list( CT = expression(C[T]), betaN = expression(beta[N]), betaT = expression(beta[T]), betaTN = expression(tilde(beta)[T]), rho = expression(rho), rhoN = expression(tilde(rho)), c1 = expression(C[1]), c2 = expression(C[2]), c1N = expression(tilde(C)[1]), c2N = expression(tilde(C)[2]) ); symbolList <- list( CT = "$C_{T}$", betaN = "$\\beta_{N}$", betaT = "$\\beta_{T}$", betaTN = "$\\tilde{\\beta}_{T}$", rho = "$\\rho$", rhoN = "$\\tilde{\\rho}$", c1 = "$C_{1}$", c2 = "$C_{2}$", c1N = "$\\tilde{C}_{1}$", c2N = "$\\tilde{C}_{2}$" ); %> \begin{document} \maketitle \begin{abstract} This is a quality control (QC) report on the paired tumor-normal sample '<%=toLatex(sampleName)%>' in data set '<%=toLatex(dataSet)%>'. \end{abstract} \tableofcontents \clearpage %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % DATA %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \chapter{Introduction} \chapter{Data} \label{ch:Data} \section{Samples} \section{Microarray data} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % METHODS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \chapter{Methods} \label{ch:Methods} \section{Segmentation} \label{sec:Segmentation} We use the Paired PSCBS segmentation method~\citep{OlshenA_etal_2011} with TumorBoost normalization~\citep{BengtssonH_etal_2010} to partion the genome into segments such that all signals in a particular segment are likely to originate from the same underlying parent-specific copy-number state. Germline genotypes are called based on the normal allele B fractions (BAFs), cf.~\citet{BengtssonH_etal_2010}. <%-- \section{Post-segmentation pruning} \label{sec:PostSegmentationPruning} <% fitP <- pruneByHClust(fit, h=0.25); #print(fitP); %> --%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % RESULTS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % WHOLE-GENOME RESULTS % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \chapter{Whole-Genome Results} \label{ch:WholeGenomeResults} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SUMMARY ANNOTATION AND GENOTYPE CALLS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% summaryOfAnnotationAndGenotypeCalls <- function(fit, ...) { %> \section{Summary of annotation and genotype calls} <% data <- getLocusData(fit, fields="full"); nbrOfLoci <- nrow(data); nbrOfSNPs <- sum(data$isSNP, na.rm=TRUE); nbrOfHets <- sum(data$isHet, na.rm=TRUE); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{table}[htbp] \begin{center} \begin{tabular}{lrr} Description & Count & Fraction \\ \hline Number of loci & <%=nbrOfLoci%> & 100.00\% \\ Number of SNPs & <%=nbrOfSNPs%> & <%=sprintf("%.2f", 100*nbrOfSNPs/nbrOfLoci)%>\% \\ Number of heterozygous SNPs* & <%=nbrOfHets%> & <%=sprintf("%.2f", 100*nbrOfHets/nbrOfSNPs)%>\% \\ Number of non-polymorphic loci & <%=nbrOfLoci-nbrOfSNPs%> & <%=sprintf("%.2f", 100*(1-nbrOfSNPs/nbrOfLoci))%>\% \\ Number of chromosomes & <%=nbrOfChromosomes%> & - \\ \end{tabular} \caption{ Summary of the locus-level data on <%=chromosomesH%>. A locus is considered to be a SNP if it has either a non-missing BAF for either the tumor or the normal. (*) Genotype calls are based on (whole-genome) naive genotyping of the germline BAFs. } \label{tbl:LocusStats} \end{center} \end{table} <% } # summaryOfAnnotationAndGenotypeCalls() %> <%=summaryOfAnnotationAndGenotypeCalls(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SIGNAL DENSITIES % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% signalDensities <- function(fit, ...) { %> <% if (!REPORT_DENSITIES) return(); %> \clearpage \section{Signal densities} \label{sec:SignalDensities} <% require("ggplot2") || throw("Package not loaded: ggplot2"); data <- getLocusData(fit, fields="full"); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> <% if (nrow(data) >= 2L) { %> \begin{figure}[htbp] \begin{center} <% fields <- c("CT", "betaN", "betaT", "rho", "c1", "c2", "betaTN", "rhoN", "c1N", "c2N"); fields <- intersect(fields, colnames(data)) %> <% for (ff in fields) { %> <% symbol <- symbolList[[ff]]; panelTitle <- switch(ff, CT="\\TCN", betaN="\\BAFN", betaT="\\BAFT", betaTN="\\BAFTN", "NNN"); lim <- switch(ff, CT=ClimX, c1=ClimX, c2=ClimX, c1N=ClimX, c2N=ClimX, BlimX); nbrOfSNPs <- sum(data$isSNP, na.rm=TRUE) %> \raisebox{4ex}{<%=symbol%>} <% for (by in c("all", "muN")) { %> <% tags <- c(chrsTags, by, ff); %> \resizebox{0.33\textwidth}{!}{% \includegraphics{<%={ toPNG(name=sampleName, tags=tags, width=640, aspectRatio=0.3, { gg <- ggplot(data, aes_string(x=ff, y="..count..")); if (by == "all") { if (ff == "CT" && nbrOfSNPs > 0 && any(!data$isSNP, na.rm=TRUE)) { gg <- gg + aes(group=type, colour=type); } } else if (by == "muN") { gg <- gg + aes_string(group="muNx", colour="muNx"); gg <- gg + scale_color_manual(values=muNCols); } # See https://github.com/hadley/ggplot2/wiki/Legend-Attributes gg <- gg + theme(legend.position=c(0.97, 0.75), legend.justification = 1, legend.direction="vertical", legend.title=element_text(size=0), legend.text=element_text(size=16)); gg <- gg + geom_density(size=2, na.rm=TRUE); gg <- gg + xlab(NULL); gg <- gg + ylab(NULL); gg <- gg + xlim(lim); gg <- gg + theme(axis.text.x=xnbrOpts, axis.text.y=ynbrOpts); gg <- gg + theme(axis.title.x=xlabOpts, axis.title.y=ylabOpts); suppressWarnings({ print(gg); }); }, force=FALSE); }%>}% }% <% } # for (by ...) %> \\ % <% } # for (ff ...) %> \end{center} \caption{ Density estimates of locus-level signals on <%=chromosomesH%> with and without TumorBoost normalization. The signals in the left and right panels are without and with stratification on genotype calls (AA and BB in gray and AB in black). We expect to see three genotype groups for the normal BAFs ($\beta_{N}$). The tumor BAFs ($\beta_{T}$) should be more distinct after normalization ($\tilde{\beta}_{T}$), particularly for homozygous SNPs. If there are no allelic imbalances in the tumor, then the density of the tumor should be similar to that of the normal. } \label{fig:SignalDensity} \end{figure} <% } else { %> NOTE: No density plots produced for <%= chromosomesH %> because there are fewer than two loci. <% } ## if (nrow(data) >= 2L) %> <% } # signalDensities() %> <%=signalDensities(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % BEFORE AND AFTER TUMORBOOST % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% beforeAndAfterTumorBoost <- function(fit, ...) { %> <% data <- getLocusData(fit, fields="full"); ## Nothing to do? if (!all(is.element(c("betaN", "betaT", "type"), colnames(data)))) return() %> <% if (!REPORT_TUMORBOOST) return(); %> \clearpage \section{Before and after TumorBoost} \label{sec:BeforeAndAfterTumorBoost} \begin{figure}[htbp] \begin{center} <% require("ggplot2") || throw("Package not loaded: ggplot2"); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> <% dataT <- subset(data, type == "SNP"); %> <% for (ff in c("betaT", "betaTN")) { %> \resizebox{0.40\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, sprintf("%s-vs-betaN", ff)); toPNG(name=sampleName, tags=tags, width=640, aspectRatio=0.85, { gg <- ggplot(dataT, aes_string(x="betaN", y=ff)); gg <- gg + aes_string(group="muNx", colour="muNx"); gg <- gg + scale_color_manual(values=muNCols); # See https://github.com/hadley/ggplot2/wiki/Legend-Attributes gg <- gg + theme(#legend.position=c(0.97, 0.85), #legend.justification = 1, legend.direction="vertical", legend.title=element_text(size=0), legend.text=element_text(size=16)); if (REPORT_USE_ALPHA_CHANNEL) { gg <- gg + geom_point(alpha=min(10e3/nrow(dataT), 0.5), na.rm=TRUE); } else { gg <- gg + geom_point(na.rm=TRUE); } gg <- gg + xlab(labList[["betaN"]]) + ylab(labList[[ff]]); gg <- gg + xlim(BlimX) + ylim(BlimX); gg <- gg + theme(axis.text.x=xnbrOpts, axis.text.y=ynbrOpts); gg <- gg + theme(axis.title.x=xlabOpts, axis.title.y=ylabOpts); print(gg); }); }%>}% }% <% } # for (ff ...) %> \end{center} \caption{ Tumor-normal BAFs before (left) and after (right) TumorBoost normalization on <%=chromosomesH%>. We expect to see only two homozygote groups. If there are more, then the tumor and the normal BAFs are not from the same individual. If there are no allelic imbalances in the tumor, then there is also only one heterozygous group. } \label{fig:BAFBAF} \end{figure} <% } # beforeAndAfterTumorBoost() %> <%=beforeAndAfterTumorBoost(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % PARENT-SPECIFIC COPY-NUMBER SEGMENTATION TRACKS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% pscnSegmentationTracks <- function(fit, ...) { %> \clearpage \section{Parent-specific copy-number segmentation tracks} \label{sec:PSCNSegmentationTracks} <% chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} <% for (track in c("tcn", "dh", "tcn,c1,c2")) { %> <%-- <% for (track in c("tcn*", "betaT", "betaTN*", "dh*", "tcn*,c1*,c2-*")) { %> --%> \resizebox{\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, "PairedPSCBS", gsub("[*-]", "", track), getChecksum(fit)); toPNG(name=sampleName, tags=tags, width=1024, aspectRatio=0.25, par=list(mar=c(2.8,4,1,1)+0.1, cex=1.5), { plotTracks(fit, tracks=track, lwd=5, Clim=Clim); # plotTrack2(fit, panels=track, lwd=5, Clim=Clim); }, force=FALSE); }%>}% }% \\ <% } # for (track ...) %> \end{center} \caption{ Results of Paired PSCBS segmentation on <%=chromosomesH%> projected onto TCN (top), \BAFT (row 2), \BAFTN (row 3), DH (row 4), as well as TCN, $C_1$ and $C_2$ (bottom). Paired PSCBS segmentation is always done on TCN and DH data. There are in total $S=<%=nbrOfSegments(fit, splitters=FALSE)%>$ segments. } \label{fig:PairedPSCBS} \end{figure} <% } # pscnSegmentationTracks() %> <%=pscnSegmentationTracks(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % PARENT-SPECIFIC COPY-NUMBER TRANSITIONS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% pscnSegmentationTransitions <- function(fit, ...) { %> <% if (!REPORT_C1C2) return(); %> \clearpage \section{Parent-specific copy-number transitions} \label{sec:PSCNSegmentationTransitions} <% # plotC1C2Grid() require("aroma.cn") || throw("Package not loaded: aroma.cn"); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} \resizebox{0.6\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, "PairedPSCBS", "C1C2", getChecksum(fit)); toPNG(name=sampleName, tags=tags, width=640, aspectRatio=1, par=list(mar=c(4,4,1,1)+0.1, cex=2), { plotC1C2Grid(fit, Clim=ClimX); linesC1C2(fit, lwd=2); }, force=FALSE); }%>}% }% \end{center} \caption{ A graph representation of the minor ($C_1$) and major ($C_2$) copy-number segmentation on <%=chromosomesH%>, where the nodes represent ($S=<%=nbrOfSegments(fit, splitters=FALSE)%>$) segments and the lines change points. The size of a node reflects the length of the corresponding segment. The marginal distributions (gray curves) of the minor and the major CNs are projected onto the horizontal and vertical axis, respectively. To easy a visual comparison, the latter is also projected onto the horizontal axis (light blue curve). } \label{fig:C1C2} \end{figure} <% } # pscnSegmentationTransitions() %> <%=pscnSegmentationTransitions(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % NORMAL CONTAMINATION % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% pscnNormalContamination <- function(fit, ...) { %> \clearpage \section{Normal contamination} \label{sec:PSCNNormalContamination} <% ## Attempt to estimate kappa kappa <- tryCatch(estimateKappa(fit, ...), error = identity) if (inherits(kappa, "error")) { %> The estimation of normal contamination failed, which typically happens when the parent-specific copy numbers are too noisy or when there are too few parent-specific copy-number events occuring in the tumor. Details: The reason reported by \code{estimateKappa()} was: <%= conditionMessage(kappa) %>. <% } else { %> The estimated amount of normal contamination of this sample is <%= sprintf("%.1f", 100*kappa) %>\% ($\kappa = <%= sprintf("%.3f", kappa) %>$). This estimate, which is provided due to popular demand, is also affected by other types of background signals, which may be specific to sample or batch. Because of this, great care should be taken when interpreting this estimate and using it in downstream analysis. Being conservative, we recommend to \emph{not} to use it as an accurate estimate of the \emph{true} amount of normal contamination. However, if the sample and batch-specific effects are small, estimates from multiple samples may compared with each other, i.e. samples can be ranked by their \emph{relative amount of normal contamination} (which might be done also when the absolute values cannot be trusted). <% } %> <% } # pscnNormalContamination() %> <%=pscnNormalContamination(fit)%> % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = <% if (REPORT_PER_CHROMOSOME && nbrOfChromosomes(fit) > 1) { %> <% for (chr in getChromosomes(fit)) { %> \chapter{Chromosome <%=chr%> Results} \label{sec:Chromosome<%=chr%>Results} <% fitT <- extractChromosome(fit, chromosome=chr); %> <%=summaryOfAnnotationAndGenotypeCalls(fitT)%> <%=signalDensities(fitT)%> <%=beforeAndAfterTumorBoost(fitT)%> <%=pscnSegmentationTracks(fitT)%> <%=pscnSegmentationTransitions(fitT)%> <% } # for (chr ...) %> <% } # if (REPORT_PER_CHROMOSOME && nbrOfChromosomes(fit) > 1) %> <%-- % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: WHOLE-GENOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \section{Hierarchical pruning} \label{sec:HierarchicalPruning} % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = --%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % REFERENCES %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % \clearpage \bibliography{bioinformatics-journals-abbr,PSCBS} %\bibliographystyle{plain} \bibliographystyle{natbib} \appendix \chapter{Appendix} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Session information %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % \clearpage \section*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using \code{rsp()} of the R.rsp package. The template for this report was created by Henrik Bengtsson on April 20, 2012. \end{document} <% } # pairedPSCBSReport() %> <%=do.call("pairedPSCBSReport", args=rspArgs)%> <% ###################################################################### # RSP CLOSEUP ###################################################################### # Function for renaming report afterwards assign("renamePDF", function() { filename <- sprintf("%s,report.pdf", studyName); pathname <- file.path(reportPath, filename); file.rename("report.pdf", pathname); }, envir=globalenv()); %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % HISTORY: % 2016-05-11 % o Updated to handle PairedPSCBS objects with only 'rho' but no % 'betaN' and 'betaT'. % 2014-05-24 % o Replaced a deprecated opts() of ggplot2 with theme(). % 2013-10-18 % o BUG FIX: Report template assumed that R.utils was attached. % 2012-11-03 % o Replaced deprecated ggplot2 functions. % 2012-09-16 % o Added easy report configuration at the very top. % 2012-05-30 % o Removed ggplot2 warnings on missing values. % 2012-02-28 % o Now it is possible to turn off usage of the alpha channel in % plots, e.g. setOption("PSCBS::report/useAlphaChannel", FALSE). % This is useful for if the alpha channel is not supported. % 2012-02-27 % o First successful run with real data. % o Now all of the report uses a PairedPSCBS object. % o Now making more use of templates. % o Now passing a data frame to segmentByPairedCBS(). % 2011-09-30 % o Created. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% ��������������������������������������������������������PSCBS/inst/templates/rsp/natbib.bst�����������������������������������������������������������������0000644�0001762�0000144�00000063160�14564051545�016673� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%% %% This is file `natbib.bst', generated %% on <1994/9/16> with the docstrip utility (2.2h). %% %% The original source files were: %% %% genbst.mbs (with options: `ay,nat,seq-lab,nm-rev,dt-beg,yr-par,vol-bf, %% volp-com,etal-it') %% ---------------------------------------- %% *** Personal bib style, PWD *** %% %% (Here are the specifications of the source file) %% \ProvidesFile{genbst.mbs}[1994/09/16 1.5 (PWD)] %% For use with BibTeX version 0.99a or later %% and with LaTeX 2.09 or 2e %%------------------------------------------------------------------- %% NOTICE: %% This file may be used for non-profit purposes. %% It may not be distributed in exchange for money, %% other than distribution costs. %% %% The author provides it `as is' and does not guarantee it in any way. %% %% Copyright (C) 1994 Patrick W. Daly %% Max-Planck-Institut f\"ur Aeronomie %% Postfach 20 %% D-37189 Katlenburg-Lindau %% Germany %% %% E-mail: %% SPAN-- nsp::linmpi::daly (note nsp also known as ecd1) %% Internet-- daly@linmpi.dnet.gwdg.de %%----------------------------------------------------------- %% \CharacterTable %% {Upper-case \A\B\C\D\E\F\G\H\I\J\K\L\M\N\O\P\Q\R\S\T\U\V\W\X\Y\Z %% Lower-case \a\b\c\d\e\f\g\h\i\j\k\l\m\n\o\p\q\r\s\t\u\v\w\x\y\z %% Digits \0\1\2\3\4\5\6\7\8\9 %% Exclamation \! Double quote \" Hash (number) \# %% Dollar \$ Percent \% Ampersand \& %% Acute accent \' Left paren \( Right paren \) %% Asterisk \* Plus \+ Comma \, %% Minus \- Point \. Solidus \/ %% Colon \: Semicolon \; Less than \< %% Equals \= Greater than \> Question mark \? %% Commercial at \@ Left bracket \[ Backslash \\ %% Right bracket \] Circumflex \^ Underscore \_ %% Grave accent \` Left brace \{ Vertical bar \| %% Right brace \} Tilde \~} %%--------------------------------------------------------------------- % This is an author-year citation style bibliography. As such, it is % non-standard LaTeX, and requires a special package file to function properly. % Such a package is natbib.sty by Patrick W. Daly % The form of the \bibitem entries is % \bibitem[Jones et al.(1990)]{key}... % \bibitem[Jones et al.(1990)Jones, Baker, and Smith]{key}... % The essential feature is that the label (the part in brackets) consists % of the author names, as they should appear in the citation, with the year % in parentheses following. There must be no space before the opening % parenthesis! % With natbib v5.3, a full list of authors may also follow the year. % In natbib.sty, it is possible to define the type of enclosures that is % really wanted (brackets or parentheses), but in either case, there must % be parentheses in the label. % The \cite command functions as follows: % \cite{key} ==>> Jones et al. (1990) % \cite[]{key} ==>> (Jones et al., 1990) % \cite[chap. 2]{key} ==>> (Jones et al., 1990, chap. 2) % \cite[e.g.][]{key} ==>> (e.g. Jones et al., 1990) % \cite[e.g.][p. 32]{key} ==>> (e.g. Jones et al., p. 32) % \citeauthor{key} Jones et al. % \citefullauthor{key} Jones, Baker, and Smith % \citeyear{key} 1990 %%--------------------------------------------------------------------- ENTRY { address author booktitle chapter edition editor howpublished institution journal key month note number organization pages publisher school series title type volume year } {} { label extra.label sort.label } INTEGERS { output.state before.all mid.sentence after.sentence after.block } FUNCTION {init.state.consts} { #0 'before.all := #1 'mid.sentence := #2 'after.sentence := #3 'after.block := } STRINGS { s t } FUNCTION {output.nonnull} { 's := output.state mid.sentence = { ", " * write$ } { output.state after.block = { add.period$ write$ newline$ "\newblock " write$ } { output.state before.all = 'write$ { add.period$ " " * write$ } if$ } if$ mid.sentence 'output.state := } if$ s } FUNCTION {output} { duplicate$ empty$ 'pop$ 'output.nonnull if$ } FUNCTION {output.check} { 't := duplicate$ empty$ { pop$ "empty " t * " in " * cite$ * warning$ } 'output.nonnull if$ } FUNCTION {fin.entry} { add.period$ write$ newline$ } FUNCTION {new.block} { output.state before.all = 'skip$ { after.block 'output.state := } if$ } FUNCTION {new.sentence} { output.state after.block = 'skip$ { output.state before.all = 'skip$ { after.sentence 'output.state := } if$ } if$ } FUNCTION {not} { { #0 } { #1 } if$ } FUNCTION {and} { 'skip$ { pop$ #0 } if$ } FUNCTION {or} { { pop$ #1 } 'skip$ if$ } FUNCTION {non.stop} { duplicate$ "}" * add.period$ #-1 #1 substring$ "." = } FUNCTION {new.block.checkb} { empty$ swap$ empty$ and 'skip$ 'new.block if$ } FUNCTION {field.or.null} { duplicate$ empty$ { pop$ "" } 'skip$ if$ } FUNCTION {emphasize} { duplicate$ empty$ { pop$ "" } { "{\em " swap$ * non.stop { "\/}" * } { "}" * } if$ } if$ } FUNCTION {bolden} { duplicate$ empty$ { pop$ "" } { "{\bf " swap$ * "}" * } if$ } INTEGERS { nameptr namesleft numnames } FUNCTION {format.names} { 's := #1 'nameptr := s num.names$ 'numnames := numnames 'namesleft := { namesleft #0 > } { s nameptr "{vv~}{ll}{, jj}{, f.}" format.name$ 't := nameptr #1 > { namesleft #1 > { ", " * t * } { numnames #2 > { "," * } 'skip$ if$ t "others" = { " " * "et~al." emphasize * } { " and " * t * } if$ } if$ } 't if$ nameptr #1 + 'nameptr := namesleft #1 - 'namesleft := } while$ } FUNCTION {format.names.ed} { 's := #1 'nameptr := s num.names$ 'numnames := numnames 'namesleft := { namesleft #0 > } { s nameptr "{f.~}{vv~}{ll}{, jj}" format.name$ 't := nameptr #1 > { namesleft #1 > { ", " * t * } { numnames #2 > { "," * } 'skip$ if$ t "others" = { " " * "et~al." emphasize * } { " and " * t * } if$ } if$ } 't if$ nameptr #1 + 'nameptr := namesleft #1 - 'namesleft := } while$ } FUNCTION {format.key} { empty$ { key field.or.null } { "" } if$ } FUNCTION {format.authors} { author empty$ { "" } { author format.names } if$ } FUNCTION {format.editors} { editor empty$ { "" } { editor format.names editor num.names$ #1 > { ", editors" * } { ", editor" * } if$ } if$ } FUNCTION {format.in.editors} { editor empty$ { "" } { editor format.names.ed editor num.names$ #1 > { ", editors" * } { ", editor" * } if$ } if$ } FUNCTION {format.title} { title empty$ { "" } { title "t" change.case$ } if$ } FUNCTION {format.full.names} {'s := #1 'nameptr := s num.names$ 'numnames := numnames 'namesleft := { namesleft #0 > } { s nameptr "{vv~}{ll}" format.name$ 't := nameptr #1 > { namesleft #1 > { ", " * t * } { numnames #2 > { "," * } 'skip$ if$ t "others" = { " " * "et~al." emphasize * } { " and " * t * } if$ } if$ } 't if$ nameptr #1 + 'nameptr := namesleft #1 - 'namesleft := } while$ } FUNCTION {author.editor.key.full} { author empty$ { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.full.names } if$ } { author format.full.names } if$ } FUNCTION {author.key.full} { author empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { author format.full.names } if$ } FUNCTION {editor.key.full} { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.full.names } if$ } FUNCTION {make.full.names} { type$ "book" = type$ "inbook" = or 'author.editor.key.full { type$ "proceedings" = 'editor.key.full 'author.key.full if$ } if$ } FUNCTION {output.bibitem} { newline$ "\bibitem[" write$ label write$ ")" make.full.names * "]{" * write$ cite$ write$ "}" write$ newline$ "" before.all 'output.state := } FUNCTION {n.dashify} { 't := "" { t empty$ not } { t #1 #1 substring$ "-" = { t #1 #2 substring$ "--" = not { "--" * t #2 global.max$ substring$ 't := } { { t #1 #1 substring$ "-" = } { "-" * t #2 global.max$ substring$ 't := } while$ } if$ } { t #1 #1 substring$ * t #2 global.max$ substring$ 't := } if$ } while$ } FUNCTION {word.in} { "In " } FUNCTION {format.date} { year duplicate$ empty$ { "empty year in " cite$ * "; set to ????" * warning$ pop$ "????" } 'skip$ if$ before.all 'output.state := " (" swap$ * extra.label * ")" * } FUNCTION {format.btitle} { title emphasize } FUNCTION {tie.or.space.connect} { duplicate$ text.length$ #3 < { "~" } { " " } if$ swap$ * * } FUNCTION {either.or.check} { empty$ 'pop$ { "can't use both " swap$ * " fields in " * cite$ * warning$ } if$ } FUNCTION {format.bvolume} { volume empty$ { "" } { "volume" volume tie.or.space.connect series empty$ 'skip$ { " of " * series emphasize * } if$ "volume and number" number either.or.check } if$ } FUNCTION {format.number.series} { volume empty$ { number empty$ { series field.or.null } { output.state mid.sentence = { "number" } { "Number" } if$ number tie.or.space.connect series empty$ { "there's a number but no series in " cite$ * warning$ } { " in " * series * } if$ } if$ } { "" } if$ } FUNCTION {format.edition} { edition empty$ { "" } { output.state mid.sentence = { edition "l" change.case$ " edition" * } { edition "t" change.case$ " edition" * } if$ } if$ } INTEGERS { multiresult } FUNCTION {multi.page.check} { 't := #0 'multiresult := { multiresult not t empty$ not and } { t #1 #1 substring$ duplicate$ "-" = swap$ duplicate$ "," = swap$ "+" = or or { #1 'multiresult := } { t #2 global.max$ substring$ 't := } if$ } while$ multiresult } FUNCTION {format.pages} { pages empty$ { "" } { pages multi.page.check { "pages" pages n.dashify tie.or.space.connect } { "page" pages tie.or.space.connect } if$ } if$ } FUNCTION {format.vol.num.pages} { volume field.or.null bolden number empty$ 'skip$ { "(" number * ")" * * volume empty$ { "there's a number but no volume in " cite$ * warning$ } 'skip$ if$ } if$ pages empty$ 'skip$ { duplicate$ empty$ { pop$ format.pages } { ", " * pages n.dashify * } if$ } if$ } FUNCTION {format.chapter.pages} { chapter empty$ 'format.pages { type empty$ { "chapter" } { type "l" change.case$ } if$ chapter tie.or.space.connect pages empty$ 'skip$ { ", " * format.pages * } if$ } if$ } FUNCTION {format.in.ed.booktitle} { booktitle empty$ { "" } { editor empty$ { word.in booktitle emphasize * } { word.in format.in.editors * ", " * booktitle emphasize * } if$ } if$ } FUNCTION {format.thesis.type} { type empty$ 'skip$ { pop$ type "t" change.case$ } if$ } FUNCTION {format.tr.number} { type empty$ { "Technical Report" } 'type if$ number empty$ { "t" change.case$ } { number tie.or.space.connect } if$ } FUNCTION {format.article.crossref} { word.in "\cite{" * crossref * "}" * } FUNCTION {format.book.crossref} { volume empty$ { "empty volume in " cite$ * "'s crossref of " * crossref * warning$ word.in } { "Volume" volume tie.or.space.connect " of " * } if$ "\cite{" * crossref * "}" * } FUNCTION {format.incoll.inproc.crossref} { word.in "\cite{" * crossref * "}" * } FUNCTION {article} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { journal emphasize "journal" output.check format.vol.num.pages output } { format.article.crossref output.nonnull format.pages output } if$ new.block note output fin.entry } FUNCTION {book} { output.bibitem author empty$ { format.editors "author and editor" output.check editor format.key output } { format.authors output.nonnull crossref missing$ { "author and editor" editor either.or.check } 'skip$ if$ } if$ format.date "year" output.check new.block format.btitle "title" output.check crossref missing$ { format.bvolume output new.block format.number.series output new.sentence publisher "publisher" output.check address output } { new.block format.book.crossref output.nonnull } if$ format.edition output new.block note output fin.entry } FUNCTION {booklet} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.title "title" output.check new.block howpublished output address output new.block note output fin.entry } FUNCTION {inbook} { output.bibitem author empty$ { format.editors "author and editor" output.check editor format.key output } { format.authors output.nonnull crossref missing$ { "author and editor" editor either.or.check } 'skip$ if$ } if$ format.date "year" output.check new.block format.btitle "title" output.check crossref missing$ { format.bvolume output format.chapter.pages "chapter and pages" output.check new.block format.number.series output new.sentence publisher "publisher" output.check address output } { format.chapter.pages "chapter and pages" output.check new.block format.book.crossref output.nonnull } if$ format.edition output new.block note output fin.entry } FUNCTION {incollection} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { format.in.ed.booktitle "booktitle" output.check format.bvolume output format.number.series output format.chapter.pages output new.sentence publisher "publisher" output.check address output format.edition output } { format.incoll.inproc.crossref output.nonnull format.chapter.pages output } if$ new.block note output fin.entry } FUNCTION {inproceedings} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block crossref missing$ { format.in.ed.booktitle "booktitle" output.check format.bvolume output format.number.series output format.pages output address output new.sentence organization output publisher output } { format.incoll.inproc.crossref output.nonnull format.pages output } if$ new.block note output fin.entry } FUNCTION {conference} { inproceedings } FUNCTION {manual} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.btitle "title" output.check organization address new.block.checkb organization output address output format.edition output new.block note output fin.entry } FUNCTION {mastersthesis} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.btitle "title" output.check new.block "Master's thesis" format.thesis.type output.nonnull school "school" output.check address output new.block note output fin.entry } FUNCTION {misc} { output.bibitem format.authors output author format.key output format.date "year" output.check new.block format.title output new.block howpublished output new.block note output fin.entry } FUNCTION {phdthesis} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.btitle "title" output.check new.block "Ph.D. thesis" format.thesis.type output.nonnull school "school" output.check address output new.block note output fin.entry } FUNCTION {proceedings} { output.bibitem format.editors output editor format.key output format.date "year" output.check new.block format.btitle "title" output.check format.bvolume output format.number.series output address output new.sentence organization output publisher output new.block note output fin.entry } FUNCTION {techreport} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block format.tr.number output.nonnull institution "institution" output.check address output new.block note output fin.entry } FUNCTION {unpublished} { output.bibitem format.authors "author" output.check author format.key output format.date "year" output.check new.block format.title "title" output.check new.block note "note" output.check fin.entry } FUNCTION {default.type} { misc } MACRO {jan} {"January"} MACRO {feb} {"February"} MACRO {mar} {"March"} MACRO {apr} {"April"} MACRO {may} {"May"} MACRO {jun} {"June"} MACRO {jul} {"July"} MACRO {aug} {"August"} MACRO {sep} {"September"} MACRO {oct} {"October"} MACRO {nov} {"November"} MACRO {dec} {"December"} MACRO {acmcs} {"ACM Computing Surveys"} MACRO {acta} {"Acta Informatica"} MACRO {cacm} {"Communications of the ACM"} MACRO {ibmjrd} {"IBM Journal of Research and Development"} MACRO {ibmsj} {"IBM Systems Journal"} MACRO {ieeese} {"IEEE Transactions on Software Engineering"} MACRO {ieeetc} {"IEEE Transactions on Computers"} MACRO {ieeetcad} {"IEEE Transactions on Computer-Aided Design of Integrated Circuits"} MACRO {ipl} {"Information Processing Letters"} MACRO {jacm} {"Journal of the ACM"} MACRO {jcss} {"Journal of Computer and System Sciences"} MACRO {scp} {"Science of Computer Programming"} MACRO {sicomp} {"SIAM Journal on Computing"} MACRO {tocs} {"ACM Transactions on Computer Systems"} MACRO {tods} {"ACM Transactions on Database Systems"} MACRO {tog} {"ACM Transactions on Graphics"} MACRO {toms} {"ACM Transactions on Mathematical Software"} MACRO {toois} {"ACM Transactions on Office Information Systems"} MACRO {toplas} {"ACM Transactions on Programming Languages and Systems"} MACRO {tcs} {"Theoretical Computer Science"} READ FUNCTION {sortify} { purify$ "l" change.case$ } INTEGERS { len } FUNCTION {chop.word} { 's := 'len := s #1 len substring$ = { s len #1 + global.max$ substring$ } 's if$ } FUNCTION {format.lab.names} { 's := s #1 "{vv~}{ll}" format.name$ s num.names$ duplicate$ #2 > { pop$ " " * "et~al." emphasize * } { #2 < 'skip$ { s #2 "{ff }{vv }{ll}{ jj}" format.name$ "others" = { " " * "et~al." emphasize * } { " and " * s #2 "{vv~}{ll}" format.name$ * } if$ } if$ } if$ } FUNCTION {author.key.label} { author empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { author format.lab.names } if$ } FUNCTION {author.editor.key.label} { author empty$ { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.lab.names } if$ } { author format.lab.names } if$ } FUNCTION {editor.key.label} { editor empty$ { key empty$ { cite$ #1 #3 substring$ } 'key if$ } { editor format.lab.names } if$ } FUNCTION {calc.label} { type$ "book" = type$ "inbook" = or 'author.editor.key.label { type$ "proceedings" = 'editor.key.label 'author.key.label if$ } if$ "(" * year duplicate$ empty$ { pop$ "????" } { purify$ #-1 #4 substring$ } if$ * 'label := } FUNCTION {sort.format.names} { 's := #1 'nameptr := "" s num.names$ 'numnames := numnames 'namesleft := { namesleft #0 > } { nameptr #1 > { " " * } 'skip$ if$ s nameptr "{vv{ } }{ll{ }}{ f{ }}{ jj{ }}" format.name$ 't := nameptr numnames = t "others" = and { "et al" * } { numnames #2 > nameptr #2 = and { "zzzzzz" * #1 'namesleft := } { t sortify * } if$ } if$ nameptr #1 + 'nameptr := namesleft #1 - 'namesleft := } while$ } FUNCTION {sort.format.title} { 't := "A " #2 "An " #3 "The " #4 t chop.word chop.word chop.word sortify #1 global.max$ substring$ } FUNCTION {author.sort} { author empty$ { key empty$ { "to sort, need author or key in " cite$ * warning$ "" } { key sortify } if$ } { author sort.format.names } if$ } FUNCTION {author.editor.sort} { author empty$ { editor empty$ { key empty$ { "to sort, need author, editor, or key in " cite$ * warning$ "" } { key sortify } if$ } { editor sort.format.names } if$ } { author sort.format.names } if$ } FUNCTION {editor.sort} { editor empty$ { key empty$ { "to sort, need editor or key in " cite$ * warning$ "" } { key sortify } if$ } { editor sort.format.names } if$ } FUNCTION {presort} { calc.label label sortify " " * type$ "book" = type$ "inbook" = or 'author.editor.sort { type$ "proceedings" = 'editor.sort 'author.sort if$ } if$ #1 entry.max$ substring$ 'sort.label := sort.label * " " * title field.or.null sort.format.title * #1 entry.max$ substring$ 'sort.key$ := } ITERATE {presort} SORT STRINGS { last.label next.extra } INTEGERS { last.extra.num } FUNCTION {initialize.extra.label.stuff} { #0 int.to.chr$ 'last.label := "" 'next.extra := #0 'last.extra.num := } FUNCTION {forward.pass} { last.label label = { last.extra.num #1 + 'last.extra.num := last.extra.num int.to.chr$ 'extra.label := } { "a" chr.to.int$ 'last.extra.num := "" 'extra.label := label 'last.label := } if$ } FUNCTION {reverse.pass} { next.extra "b" = { "a" 'extra.label := } 'skip$ if$ extra.label 'next.extra := label extra.label * 'label := } EXECUTE {initialize.extra.label.stuff} ITERATE {forward.pass} REVERSE {reverse.pass} FUNCTION {bib.sort.order} { sort.label " " * year field.or.null sortify * " " * title field.or.null sort.format.title * #1 entry.max$ substring$ 'sort.key$ := } ITERATE {bib.sort.order} SORT FUNCTION {begin.bib} { preamble$ empty$ 'skip$ { preamble$ write$ newline$ } if$ "\begin{thebibliography}{}" write$ newline$ } EXECUTE {begin.bib} EXECUTE {init.state.consts} ITERATE {call.type$} FUNCTION {end.bib} { newline$ "\end{thebibliography}" write$ newline$ } EXECUTE {end.bib} %% End of customized bst file ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/CBS,report.tex.rsp���������������������������������������������������������0000644�0001762�0000144�00000033643�14564051545�020171� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Authors: Henrik Bengtsson % Created on: 2011-09-30 % Last updated: 2012-02-27 % % Usage: (compiles *.tex.rsp => tex.rsp.R => *.tex => *.dvi) % R.rsp::rsp("CBS.tex.rsp", path="reports,rsp/"); %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% <% library("PSCBS"); library("R.devices"); library("R.cache"); library("R.utils"); # setOption() stopifnot(exists("rspArgs", mode="list")); %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % LATEX STARTUP %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \documentclass[twoside,12pt]{report} \usepackage{fancyvrb} \usepackage{xspace} \usepackage{subfigure} % \subfigure[<title>]{} \usepackage[round]{natbib} \addtolength{\oddsidemargin}{-0.5in} \addtolength{\evensidemargin}{-0.5in} \addtolength{\textwidth}{1in} \addtolength{\topmargin}{-0.8in} \addtolength{\textheight}{1.3in} \renewcommand{\topfraction}{1.00} % max fraction of floats at top \renewcommand{\bottomfraction}{1.0} % max fraction of floats at bottom \renewcommand{\textfraction}{0.00} \usepackage{fancyhdr} \pagestyle{fancy} %% \fancyhead{} % clear all header fields %% \fancyfoot{} % clear all footer fields %% \fancyhead[LE,RO]{\slshape \rightmark} %% \fancyfoot[C]{\thepage} \fancyhf{} \fancyhead[LE,RO]{\thepage} \fancyhead[RE]{\textit{\nouppercase{\leftmark}}} \fancyhead[LO]{\textit{\nouppercase{\rightmark}}} \newcommand{\code}[1]{\texttt{#1}\xspace} \newcommand{\TCN}{TCN\xspace} \newcommand{\BAF}{\BAF\xspace} \newcommand{\BAFN}{BAF$_{N}$\xspace} \newcommand{\BAFT}{BAF$_{T}$\xspace} \newcommand{\BAFTN}{BAF$^*_{T}$\xspace} <% cbsReport <- function(fit, sampleName=NULL, dataSet=NULL, studyName="CBS", Clim=c(0,4), reportPath=file.path("reports", studyName), figPath=file.path(reportPath, "figures"), ..., figForce=FALSE) { %> <% # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Validate arguments # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Argument 'fit': fit <- Arguments$getInstanceOf(fit, "CBS"); # Argument 'sampleName': if (is.null(sampleName)) { sampleName <- sampleName(fit); } sampleName <- Arguments$getCharacter(sampleName); # Argument 'dataSet': if (!is.null(dataSet)) { dataSet <- Arguments$getCharacter(dataSet); } # Argument 'studyName': studyName <- Arguments$getCharacter(studyName); # Argument 'reportPath': reportPath <- Arguments$getWritablePath(reportPath); # Argument 'figPath': figPath <- Arguments$getWritablePath(figPath); # Argument 'figForce': figForce <- Arguments$getLogical(figForce); %> <% oFigPath <- setOption("devEval/args/path", figPath); on.exit({ setOption("devEval/args/path", oFigPath); }, add=TRUE); oPar <- setOption("devNew/args/par", list(lwd=2)); on.exit({ setOption("devNew/args/par", oPar); }, add=TRUE); %> <% studyLbl <- sprintf("Study: %s\\\\", toLatex(studyName)); if (!is.null(dataSet)) { dataSetLbl <- sprintf("Data set: %s\\\\", toLatex(dataSet)); } else { dataSetLbl <- ""; } %> \title{CBS Report:\\<%=studyLbl%><%=dataSetLbl%>Sample: <%=toLatex(sampleName)%>} \author{Report template by Henrik Bengtsson} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % GRAPHICS SETTINGS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% setOption("devEval/args/force", figForce); %> \usepackage{graphicx} \graphicspath{{<%=figPath%>/} {../<%=figPath%>/}} <% # GGPLOT2 SETTINGS ClimX <- Clim + c(-1,1)*diff(Clim)*0.08; muNCols <- c("#999999", "#000000", "#999999"); require("ggplot2") || throw("Package not loaded: ggplot2"); xnbrOpts <- element_text(colour="grey50", size=20, hjust=1, lineheight=0.9); ynbrOpts <- element_text(colour="grey50", size=20, vjust=1, lineheight=0.9); xlabOpts <- element_text(colour="black", size=28, hjust=0.5); ylabOpts <- element_text(colour="black", size=28, vjust=0.5, angle=90); labList <- list( CT = expression(C[T]), betaN = expression(beta[N]), betaT = expression(beta[T]), betaTN = expression(tilde(beta)[T]), rho = expression(rho), rhoN = expression(tilde(rho)), c1 = expression(C[1]), c2 = expression(C[2]), c1N = expression(tilde(C)[1]), c2N = expression(tilde(C)[2]) ); symbolList <- list( CT = "$C_{T}$", betaN = "$\\beta_{N}$", betaT = "$\\beta_{T}$", betaTN = "$\\tilde{\\beta}_{T}$", rho = "$\\rho$", rhoN = "$\\tilde{\\rho}$", c1 = "$C_{1}$", c2 = "$C_{2}$", c1N = "$\\tilde{C}_{1}$", c2N = "$\\tilde{C}_{2}$" ); %> \begin{document} \maketitle \begin{abstract} This is a quality control (QC) report on the sample '<%=toLatex(sampleName)%>' in data set '<%=toLatex(dataSet)%>'. \end{abstract} \tableofcontents \clearpage %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % DATA %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \chapter{Introduction} \chapter{Data} \label{ch:Data} \section{Samples} \section{Microarray data} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % METHODS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \chapter{Methods} \label{ch:Methods} \section{Segmentation} \label{sec:Segmentation} We use the CBS segmentation method~\citep{OlshenA_etal_2007} to partion the genome into segments such that all signals in a particular segment are likely to originate from the same underlying total copy-number state. <%-- \section{Post-segmentation pruning} \label{sec:PostSegmentationPruning} <% fitP <- pruneByHClust(fit, h=0.25); #print(fitP); %> --%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % RESULTS %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % WHOLE-GENOME RESULTS % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \chapter{Whole-Genome Results} \label{ch:WholeGenomeResults} % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SUMMARY ANNOTATION % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% summaryOfAnnotation <- function(fit, ...) { %> \section{Summary of annotation} <% data <- getLocusData(fit, fields="full"); nbrOfLoci <- nrow(data); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{table}[htbp] \begin{center} \begin{tabular}{lrr} Description & Count & Fraction \\ \hline Number of loci & <%=nbrOfLoci%> & 100.00\% \\ Number of chromosomes & <%=nbrOfChromosomes%> & - \\ \end{tabular} \caption{ Summary of the locus-level data on <%=chromosomesH%>. } \label{tbl:LocusStats} \end{center} \end{table} <% } # summaryOfAnnotation() %> <%=summaryOfAnnotation(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % SIGNAL DENSITIES % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% signalDensities <- function(fit, ...) { %> \clearpage \section{Signal densities} \label{sec:SignalDensities} <% require("ggplot2") || throw("Package not loaded: ggplot2"); data <- getLocusData(fit, fields="full"); chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> <% if (nrow(data) >= 2L) { %> \begin{figure}[htbp] \begin{center} <% fields <- c("y"); %> <% for (ff in fields) { %> <% symbol <- symbolList[[ff]]; panelTitle <- switch(ff, y="\\TCN", CT="\\TCN", betaN="\\BAFN", betaT="\\BAFT", betaTN="\\BAFTN", "NNN"); lim <- switch(ff, y=ClimX, CT=ClimX, c1=ClimX, c2=ClimX, c1N=ClimX, c2N=ClimX); %> \raisebox{4ex}{<%=symbol%>} <% for (by in c("all")) { %> <% tags <- c(chrsTags, by, ff); %> \resizebox{0.33\textwidth}{!}{% \includegraphics{<%={ toPNG(name=sampleName, tags=tags, width=640, aspectRatio=0.3, { gg <- ggplot(data, aes_string(x=ff, y="..count..")); if (by == "all") { if (ff == "CT" && any(!data$isSNP, na.rm=TRUE)) { gg <- gg + aes(group=type, colour=type); } } # See https://github.com/hadley/ggplot2/wiki/Legend-Attributes gg <- gg + theme(legend.position=c(0.97, 0.75), legend.justification = 1, legend.direction="vertical", legend.title=element_text(size=0), legend.text=element_text(size=16)); gg <- gg + geom_density(size=2, na.rm=TRUE); gg <- gg + xlab(NULL); gg <- gg + ylab(NULL); gg <- gg + xlim(lim); gg <- gg + theme(axis.text.x=xnbrOpts, axis.text.y=ynbrOpts); gg <- gg + theme(axis.title.x=xlabOpts, axis.title.y=ylabOpts); suppressWarnings({ print(gg); }); }, force=FALSE); }%>}% }% <% } # for (by ...) %> \\ % <% } # for (ff ...) %> \end{center} \caption{ Density estimates of locus-level signals on <%=chromosomesH%>. } \label{fig:SignalDensity} \end{figure} <% } else { %> NOTE: No density plots produced for <%= chromosomesH %> because there are fewer than two loci. <% } ## if (nrow(data) >= 2L) %> <% } # signalDensities() %> <%=signalDensities(fit)%> % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - % TOTAL COPY-NUMBER SEGMENTATION TRACKS % - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - <% tcnSegmentationTracks <- function(fit, ...) { %> \clearpage \section{Total copy-number segmentation tracks} \label{sec:TCNSegmentationTracks} <% chromosomes <- getChromosomes(fit); nbrOfChromosomes <- length(chromosomes); chromosomesH <- seqToHumanReadable(chromosomes); chromosomesH <- if (nbrOfChromosomes == 1) { sprintf("Chr %s", chromosomesH); } else { sprintf("Chrs %s", chromosomesH); } chrsTags <- if (nbrOfChromosomes == 1) { sprintf("chr%02d", chromosomes[1]); } else { sprintf("chrs%02d-%02d", min(chromosomes), max(chromosomes)); } %> \begin{figure}[htbp] \begin{center} <% for (track in c("tcn")) { %> \resizebox{\textwidth}{!}{% \includegraphics{<%={ tags <- c(chrsTags, "CBS", gsub("[*-]", "", track), getChecksum(fit)); toPNG(name=sampleName, tags=tags, width=1024, aspectRatio=0.25, par=list(mar=c(2.8,4,1,1)+0.1, cex=1.5), { plotTracks(fit, tracks=track, lwd=5, Clim=Clim); }, force=FALSE); }%>}% }% \\ <% } # for (track ...) %> \end{center} \caption{ Results of CBS segmentation on <%=chromosomesH%> projected onto TCN. There are in total $S=<%=nbrOfSegments(fit, splitters=FALSE)%>$ segments. } \label{fig:CBS} \end{figure} <% } # tcnSegmentationTracks() %> <%=tcnSegmentationTracks(fit)%> % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = <% if (nbrOfChromosomes(fit) > 1) { %> <% for (chr in getChromosomes(fit)) { %> \chapter{Chromosome <%=chr%> Results} \label{sec:Chromosome<%=chr%>Results} <% fitT <- extractChromosome(fit, chromosome=chr); %> <%=summaryOfAnnotation(fitT)%> <%=signalDensities(fitT)%> <%=tcnSegmentationTracks(fitT)%> <% } # for (chr ...) %> <% } # if (nbrOfChromosomes(fit) > 1) %> <%-- % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: WHOLE-GENOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = \section{Hierarchical pruning} \label{sec:HierarchicalPruning} % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = % PRUNED: PER CHROMOSOME SEGMENTATION % = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = --%> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % REFERENCES %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % \clearpage \bibliography{bioinformatics-journals-abbr,PSCBS} %\bibliographystyle{plain} \bibliographystyle{natbib} \appendix \chapter{Appendix} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Session information %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % \clearpage \section*{Session information} <%=toLatex(sessionInfo())%> This report was automatically generated using the R.rsp package. The template for this report was created by Henrik Bengtsson. \end{document} <% } # cbsReport() %> <%=do.call("cbsReport", args=rspArgs)%> <% ###################################################################### # RSP CLOSEUP ###################################################################### # Function for renaming report afterwards assign("renamePDF", function() { filename <- sprintf("%s,report.pdf", studyName); pathname <- file.path(reportPath, filename); file.rename("report.pdf", pathname); }, envir=globalenv()); %> %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % HISTORY: % 2013-10-18 % o BUG FIX: Report template assumed that R.utils was attached. % 2012-11-03 % o Replaced deprecated ggplot2 functions. % 2012-02-28 % o Now it is possible to turn off usage of the alpha channel in % plots, e.g. setOption("PSCBS::report/useAlphaChannel", FALSE). % This is useful for if the alpha channel is not supported. % 2012-02-27 % o First successful run with real data. % o Now all of the report uses a PairedPSCBS object. % o Now making more use of templates. % o Now passing a data frame to segmentByPairedCBS(). % 2011-09-30 % o Created. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% ���������������������������������������������������������������������������������������������PSCBS/inst/templates/rsp/PSCBS.bib������������������������������������������������������������������0000644�0001762�0000144�00000015413�14564051545�016250� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������@ARTICLE{BengtssonH_etal_2010, author = {Henrik Bengtsson and Pierre Neuvial and Terence P Speed}, title = {{TumorBoost}: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays}, journal = {BMC Bioinformatics}, year = {2010}, volume = {11}, pages = {245}, number = {1}, month = {May}, abstract = {ABSTRACT: BACKGROUND: High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH) analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses. RESULTS: We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances. CONCLUSIONS: TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH) in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific) CRMA v2 for Affymetrix or BeadStudio's (proprietary) XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package aroma.cn, which is part of the Aroma Project (http://www.aroma-project.org/).}, doi = {10.1186/1471-2105-11-245}, file = {:BengtssonH_etal_2010-TumorBoost.pdf:PDF}, language = {eng}, medline-pst = {aheadofprint}, owner = {hb}, pii = {1471-2105-11-245}, pmid = {20462408}, timestamp = {2010.05.15}, url = {http://dx.doi.org/10.1186/1471-2105-11-245} } @ARTICLE{OlshenA_etal_2011, author = {Adam B. Olshen and Henrik Bengtsson and Pierre Neuvial and Paul Spellman and Richard A. Olshen and Venkatraman E. Seshan}, title = {Parent-specific copy number in paired tumor-normal studies using circular binary segmentation}, journal = {Bioinformatics}, year = {2011}, volume = {27}, pages = {2038-2046}, number = {15}, doi = {10.1093/bioinformatics/btr329}, pmid = {21666266}, url = {http://bioinformatics.oxfordjournals.org/content/27/15/2038} } @ARTICLE{VenkatramanOlshen_2007, author = {E. S. Venkatraman and Adam B Olshen}, title = {{A} faster circular binary segmentation algorithm for the analysis of array {CGH} data.}, journal = {Bioinformatics}, year = {2007}, volume = {23}, pages = {657--663}, number = {6}, month = {Mar}, abstract = {MOTIVATION: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number. The algorithm tests for change-points using a maximal t-statistic with a permutation reference distribution to obtain the corresponding P-value. The number of computations required for the maximal test statistic is O(N2), where N is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the need for a faster algorithm. RESULTS: We present a hybrid approach to obtain the P-value of the test statistic in linear time. We also introduce a rule for stopping early when there is strong evidence for the presence of a change. We show through simulations that the hybrid approach provides a substantial gain in speed with only a negligible loss in accuracy and that the stopping rule further increases speed. We also present the analyses of array CGH data from breast cancer cell lines to show the impact of the new approaches on the analysis of real data. AVAILABILITY: An R version of the CBS algorithm has been implemented in the "DNAcopy" package of the Bioconductor project. The proposed hybrid method for the P-value is available in version 1.2.1 or higher and the stopping rule for declaring a change early is available in version 1.5.1 or higher.}, doi = {10.1093/bioinformatics/btl646}, file = {VenkatramanOlshen_2007-A faster circular binary segmentation algorithm for the analysis of array CGH data.pdf:VenkatramanOlshen_2007-A faster circular binary segmentation algorithm for the analysis of array CGH data.pdf:PDF}, keywords = {Algorithms; Chromosome Mapping, methods; Gene Dosage, genetics; Oligonucleotide Array Sequence Analysis, methods; Programming Languages; Sequence Alignment, methods; Sequence Analysis, DNA, methods; Software; Time Factors}, owner = {hb}, pii = {btl646}, pmid = {17234643}, timestamp = {2007.02.02}, url = {http://dx.doi.org/10.1093/bioinformatics/btl646} } @ARTICLE{OlshenA_etal_2004, author = {Adam B Olshen and E. S. Venkatraman and Robert Lucito and Michael Wigler}, title = {Circular binary segmentation for the analysis of array-based DNA copy number data.}, journal = {Biostatistics}, year = {2004}, volume = {5}, pages = {557--572}, number = {4}, month = {Oct}, abstract = {DNA sequence copy number is the number of copies of DNA at a region of a genome. Cancer progression often involves alterations in DNA copy number. Newly developed microarray technologies enable simultaneous measurement of copy number at thousands of sites in a genome. We have developed a modification of binary segmentation, which we call circular binary segmentation, to translate noisy intensity measurements into regions of equal copy number. The method is evaluated by simulation and is demonstrated on cell line data with known copy number alterations and on a breast cancer cell line data set.}, doi = {10.1093/biostatistics/kxh008}, file = {OlshenA_etal_2004-Circular binary segmentation for the analysis of array-based DNA copy number data.pdf:OlshenA_etal_2004-Circular binary segmentation for the analysis of array-based DNA copy number data.pdf:PDF}, keywords = {Breast Neoplasms; Cell Line, Tumor; Computer Simulation; Female; Gene Dosage; Genome, Human; Humans; Olig; e Analysis; onucleotide Array Sequence; CBS}, owner = {hb}, pii = {5/4/557}, pmid = {15475419}, timestamp = {2007.07.09}, url = {http://dx.doi.org/10.1093/biostatistics/kxh008} } 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0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������AbstractCBS AppVeyor BAF BAFs BMC Bioinformatics Biostatistics CGH CMD CN Chr CxK DHs DNAcopy Fridlyand Homozygosity JxL LOH Lucito NTCN NonPairedPSCBS PSCN PairedPSCBS Pre ROH RSP Reproducibility SxK TCN TCNs TumorBoost UCSF Venkatraman Wigler abIndex adjustPloidyScale al allelic amplificationCall attachLocally averageQuantile callHooks changepoints clearCalls dgCMatrix drawChangePoints drawKnownSegments dropChangePoint dropChangePoints dropRegion dropRegions dsCMatrix et extractCNs extractChromosome extractChromosomes extractRegions extractSegments extractWIG gainCall genomewide germline getChangePoints getChromosomeOffsets getChromosomeRanges getChromosomes getLocusData getLocusSignalNames getMeanEstimators getSampleName getSegmentSizes getSegmentTrackPrefixes getSegments ggplot hclust heterozygosity heterozygous homozygosity homozygous indMatrix isLocallyPhased isSegmentSplitter lossCall macOS mergeThreeSegments mergeTwoSegments minDensity nbrOfChangePoints nbrOfChromosomes nbrOfLoci nbrOfSegments negOutlierCall nonStructure normalizeAverage normalizeDifferencesToAverage normalizeQuantileRank normalizeQuantileSpline normalizeTotalCNs normals phenotypes ploidy plotDensity plotTracks posOutlierCall pre pruneByDP pruneByHClust renameChromosomes rescaling resegment resetSegments sampleCNs sampleName segements segmentions seperately seqOfSegmentsByDP setLocusData setMeanEstimators setPloidy setSampleName setSegments shiftTCN sparseVector splitters subclasses th tileChromosomes updateMeans writeSegments writeWIG abCall ABO AbstractPSCBS addCalls addtolength adjustFor alltt alphaAB alphaDH alphaHighAI alphaTCN anyMissing appendVarArgs applyByRegion args arrowsC arrowsDeltaC asMissing aspectRatio AtNonAB attr avgDH avgTCN Bengtsson BengtssonH betaN betaT betaTN bibliographystyle BioC biocViews bionomial Blim bootstrapDHByRegion bootstrapSegmentsAndChangepoints bootstrapTCNandDHByRegion bottomfraction bottomnumber bs bst ByC calcStatsForCopyNeutralABs callAB callABandHighAI callABandLowC callAllelicBalance callAllelicBalanceByDH callAmplifications callArms callCopyNeutral callCopyNeutralByTCNofAB callExtremeAllelicImbalance callExtremeAllelicImbalanceByDH callGainNeutralLoss callGainsAndLosses callGLAO callGNL callLoci callLOH callLowC callNaiveGenotypes callNaiveHeterzygotes callNnn callNTCN callROH callSegmentationOutliers callSegments camelCase centromere centromeres cex chr ciRange citep citet className clearBootstrapSummaries clearpage Clim CMRG cn CNA columnNamesFlavor cran csN datapoint deltaAB deltaCN deltaLOH DeltaLOH deltaROH dev devEval devOptions dh dhNbrOfLoci dhSegRows dmad documentclass downsampled drawChromosomes drawConfidenceBands drawLevels dropGaps dropMissingCT dropSegmentationOutliers dt emph encodeCalls ensuremath escapeRspVerbatim estimateDeltaAB estimateDeltaCN estimateDeltaLOH estimateDeltaLOHByMinC estimateHighDHQuantileAtAB estimateKappa estimateKappaByC estimateStandardDeviation estimateTauAB estimateTauABBySmallDH estimateTauLOH estimateTauLOHByMinC etal evensidemargin exampleData exData extractByChromosome extractByChromosomes extractByRegions extractMinorMajorCNs extractSegment extractSegmentDataByLocus extractTCNAndDHs extractTotalCNs exts figTracks figTracksPruned findheterozygous findLargeGaps findNeutralCopyNumberState findPeaksAndValleys fitP fixLocations floatpagefraction footnotesize ForNonAB fullname gapsToSegments GC genomeData GenomeWideSNP getbdry getBootstrapLocusSets getCallStatistics getCallStatisticsByArms getSmoothLocusData graphicspath graphicx hclustCNs heterozygotes heterozyous hidelinks highlightArmCalls Hmisc homozygote homozygotes hrmode htp https hyperref hypersetup Ilari Illumina includegraphics installDNAcopy jj joinSegments Junsong Kirill knownCPs knownSegments listenv loadMethod loadObject lociNotPartOfSegment loh lohCall magnitutes Makefile maketitle maploc matchings matrixStats maxC meanCol memoization methodsS minLength minSize Minya multipage multisession muN MySample na NaN natbib nbrOfUnits neglectable newcommand newenvironment NextMethod nnn nnstedt normalizeTumorBoost nperm nrow nucleotides num oddsidemargin OlshenA oma onAttach oo PairedPSCNSegments parskip pdfauthor pdfborder pdfkeywords pdfproducer pdfsubject pdftitle plotTrack plotTracksManyChromosomes png postsegmentTCN preserveOrder preserveScale priorly probs pruneBySdUndo psCBS PSCBS psSegment psSegmentPaired renewcommand resegmentation resizebox rfile Rinstignore Ritu rowAlls rsp rspTags rspVerbatim Rueda sanityChecks saveObject Scheinin sdundo secBackground secData secGaps secTCNOutliers segJJ segmentations segmentByCBS segmentByNonPairedPSCBS segmentByPairedPSCBS segs sessionInfo setcounter setMethodS setOption signalType Similarily splitter startupMessage stopifnot str strOptions studyName subsetBySegments subsubsection Sys tableofcontents Talevich tauA tauAB tauB tauTCN tbn tcn tcnNbrOfHets tcnnbrOfLoci tcnNbrOfLoci tcnNbrOfSNPs tcnNbrOr tcnSegRows testROH tex textbf textfraction textheight textnormal textsl texttt textwidth thetaN thetaT tiledChromosomes tmp toLatex topfraction topmargin toPNG Tsukanov TumorBoosted TumorBoostNormalization typeOfWeights UC ucsf undoDH undoTCN unlist unTumorBoost updateBoundaries updateMeansC updateMeansTogether useAlphaChannel usepackage VenkatramanOlshen VignetteAuthor VignetteBuilder VignetteEngine VignetteIndexEntry VignetteKeyword vspace VUMC WEHI weightedMedian weightedQuantile whichVector withCapture writeLocusData xBEEF xcolor xlim xorCalls xspace Zhao L'Ecuyer NaN's psCNA segmentByNnn segRows ����������������������������������������������������������������������PSCBS/README.md�������������������������������������������������������������������������������������0000644�0001762�0000144�00000013320�15000516577�012410� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������ <div id="badges"><!-- pkgdown markup --> <a href="https://CRAN.R-project.org/web/checks/check_results_PSCBS.html"><img border="0" src="https://www.r-pkg.org/badges/version/PSCBS" alt="CRAN check status"/></a> <a href="https://github.com/HenrikBengtsson/PSCBS/actions?query=workflow%3AR-CMD-check"><img border="0" src="https://github.com/HenrikBengtsson/PSCBS/actions/workflows/R-CMD-check.yaml/badge.svg?branch=develop" alt="R CMD check status"/></a> <a href="https://github.com/HenrikBengtsson/PSCBS/actions?query=workflow%3Arevdepcheck-top"><img border="0" src="https://github.com/HenrikBengtsson/PSCBS/actions/workflows/revdepcheck-top.yaml/badge.svg?branch=develop" alt="Top reverse-dependency checks status"/></a> </div> # PSCBS: Analysis of Parent-Specific DNA Copy Numbers The PSCBS package implements the parent-specific copy-number segmentation presented in Olshen et al. (2011). Package vignette ['Parent-specific copy-number segmentation using Paired PSCBS'](https://CRAN.R-project.org/package=PSCBS/vignettes/PairedPSCBS.pdf) provides a detailed introduction for running PSCBS segmentation. It's available as: ```r vignette("PairedPSCBS", package = "PSCBS") ``` Below is an excerpt of the example found in that vignette: ```r library(PSCBS) ## Get single-chromosome example data data <- exampleData("paired.chr01") str(data) # ’data.frame’: 73346 obs. of 6 variables: # $ chromosome: int 1 1 1 1 1 1 1 1 1 1 ... # $ x : int 1145994 2224111 2319424 2543484 2926730 2941694 3084986 3155127.. # $ CT : num 1.625 1.071 1.406 1.18 0.856 ... # $ betaT : num 0.757 0.771 0.834 0.778 0.229 ... # $ CN : num 2.36 2.13 2.59 1.93 1.71 ... # $ betaN : num 0.827 0.875 0.887 0.884 0.103 ... ## Drop total copy-number outliers data <- dropSegmentationOutliers(data) ## Identify chromosome arms from data gaps <- findLargeGaps(data, minLength = 1e+06) knownSegments <- gapsToSegments(gaps) ## Parent-specific copy-number segmentation fit <- segmentByPairedPSCBS(data, knownSegments = knownSegments) ## Get segments as a data.frame segments <- getSegments(fit, simplify = TRUE) segments # chromosome tcnId dhId start end tcnNbrOfLoci tcnMean # 1 1 1 1 554484 33414619 9413 1.381375 # 2 1 1 2 33414619 86993745 17433 1.378570 # 3 1 2 1 86993745 87005243 2 3.185100 # 4 1 3 1 87005243 119796080 10404 1.389763 # 5 1 3 2 119796080 119932126 72 1.470789 # 6 1 3 3 119932126 120992603 171 1.439620 # 7 1 4 1 120992604 141510002 0 NA # 8 1 5 1 141510003 185527989 13434 2.065400 # 9 1 6 1 185527989 199122066 4018 2.707400 # 10 1 7 1 199122066 206512702 2755 2.586100 # 11 1 8 1 206512702 206521352 14 3.871900 # 12 1 9 1 206521352 247165315 15581 2.637500 # tcnNbrOfSNPs tcnNbrOfHets dhNbrOfLoci dhMean c1Mean c2Mean # 1 2765 2765 2765 0.4868 0.3544608 1.0269140 # 2 4544 4544 4544 0.5185 0.3318907 1.0466792 # 3 0 0 0 NA NA NA # 4 2777 2777 2777 0.5203 0.3333347 1.0564285 # 5 8 8 8 0.0767 0.6789900 0.7917995 # 6 52 52 52 0.5123 0.3510514 1.0885688 # 7 0 0 NA NA NA NA # 8 3770 3770 3770 0.0943 0.9353164 1.1300836 # 9 1271 1271 1271 0.2563 1.0067467 1.7006533 # 10 784 784 784 0.2197 1.0089669 1.5771331 # 11 9 9 9 0.2769 1.3998854 2.4720146 # 12 4492 4492 4492 0.2290 1.0167563 1.6207438 ## Plot copy-number tracks plotTracks(fit) ``` ![](man/figures/ex-PSCBS-paired.chr01.png) ## Parallel processing The package supports segmentation of the chromosomes in parallel (asynchronously) via [futures](https://cran.r-project.org/package=future) by adding the following ```r future::plan("multisession") ``` to the beginning of the PSCBS script. Everything else will work the same. To reset to non-parallel processing, use `future::plan("sequential")`. To configure this automatically whenever the package is loaded, see future vignette '[A Future for R: Controlling Default Future Strategy](https://CRAN.R-project.org/package=future/vignettes/future-5-startup.html)'. ## References * Bengtsson H, Neuvial P, Speed TP. TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays, BMC Bioinformatics, 2010. DOI: [10.1186/1471-2105-11-245](https://doi.org/10.1186%2F1471-2105-11-245). PMID: [20462408](https://europepmc.org/article/MED/20462408), PMCID: PMC2894037 * Olshen AB, Bengtsson H, Neuvial P, Spellman PT, Olshen RA, Seshan VA. Parent-specific copy number in paired tumor-normal studies using circular binary segmentation, Bioinformatics, 2011. DOI: [10.1093/bioinformatics/btr329](https://doi.org/10.1093%2Fbioinformatics%2Fbtr329). PMID: [21666266](https://europepmc.org/article/MED/21666266). PMCID: PMC3137217 ## Installation R package PSCBS is available on [CRAN](https://cran.r-project.org/package=PSCBS) and can be installed in R as: ```r # install.packages("BiocManager") BiocManager::install(c("aroma.light", "DNAcopy")) install.packages("PSCBS") ``` ### Pre-release version To install the pre-release version that is available in Git branch `develop` on GitHub, use: ```r remotes::install_github("HenrikBengtsson/PSCBS", ref="develop") ``` This will install the package from source. <!-- pkgdown-drop-below --> ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/build/����������������������������������������������������������������������������������������0000755�0001762�0000144�00000000000�15000517067�012224� 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g%ËÿSvHka0zê]©¢ í²oÖ÷챇w¡Yô¹;¿iËìQïìãø§Go™t– &Uµ[‡:P· ˜ Kþ-)çÀ`«6¤!üûÄûá–‚Ö€“'L¶ŒÌþ4q¶Ù†ë£™n@(Ðáý;\ÎRÃA3-Ï)[øt¾\išæ:t”sjЂó‚Zš–Úé]wý…¸x~ �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/������������������������������������������������������������������������������������������0000755�0001762�0000144�00000000000�15000477031�011674� 5����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/Non-documented_objects.Rd�����������������������������������������������������������������0000644�0001762�0000144�00000022276�15000477031�016564� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % 999.NonDocumentedObjects.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{Non-documented objects} \alias{Non-documented objects} \title{Non-documented objects} % Other missing docs \alias{extractWIG} \alias{extractWIG.AbstractCBS} \alias{extractWIG.CBS} \alias{extractWIG.PSCBS} \alias{all.equal.AbstractCBS} \alias{all.equal.CBS} \alias{applyByRegion} \alias{applyByRegion.PairedPSCBS} \alias{arrowsC1C2} \alias{arrowsC1C2.PairedPSCBS} \alias{arrowsDeltaC1C2} \alias{arrowsDeltaC1C2.PairedPSCBS} \alias{as.CBS} \alias{as.DNAcopy} \alias{as.character.CBS} \alias{as.data.frame.PSCBS} \alias{bootstrapCIs} \alias{bootstrapCIs.PairedPSCBS} \alias{bootstrapDHByRegion} \alias{bootstrapDHByRegion.PairedPSCBS} \alias{bootstrapTCNandDHByRegion} \alias{callAB} \alias{callABandHighAI} \alias{callABandHighAI.PairedPSCBS} \alias{callABandLowC1} \alias{callABandLowC1.PairedPSCBS} \alias{callAllelicBalance} \alias{callAllelicBalance.default} \alias{callAllelicBalanceByDH} \alias{callAmplifications} \alias{callArms} \alias{callArms.CBS} \alias{callExtremeAllelicImbalanceByDH} \alias{callExtremeAllelicImbalanceByDH.PairedPSCBS} \alias{callGainsAndLosses} \alias{callLOH} \alias{callLowC1ByC1} \alias{callLowC1ByC1.PairedPSCBS} \alias{callOutliers} \alias{drawCentromeres} \alias{drawCentromeres.CBS} \alias{drawChromosomes} \alias{drawChromosomes.CBS} \alias{drawConfidenceBands} \alias{drawConfidenceBands.PairedPSCBS} \alias{drawLevels} \alias{drawLevels.CBS} \alias{drawLevels.DNAcopy} \alias{drawLevels.PairedPSCBS} \alias{dropChangePoint} \alias{dropRegion} \alias{dropRegions} \alias{estimateDeltaAB} \alias{estimateDeltaABBySmallDH} \alias{estimateDeltaLOH} \alias{estimateDeltaLOHByMinC1ForNonAB} \alias{estimateHighDHQuantileAtAB} \alias{estimateHighDHQuantileAtAB.PairedPSCBS} \alias{estimateKappa} \alias{estimateKappaByC1Density} \alias{estimateMeanForDH} \alias{estimateMeanForDH.PairedPSCBS} \alias{estimateStandardDeviation} \alias{estimateStandardDeviation.DNAcopy} \alias{estimateStdDevForHeterozygousBAF} \alias{estimateStdDevForHeterozygousBAF.PairedPSCBS} \alias{extractC1C2} \alias{extractCallsByLocus} \alias{extractCallsByLocus.PairedPSCBS} \alias{extractCallsByLocus.CBS} \alias{extractChromosome} \alias{extractChromosome.AbstractCBS} \alias{extractChromosomes} \alias{extractChromosomes.AbstractCBS} \alias{extractChromosomes.CBS} \alias{extractChromosomes.PSCBS} \alias{extractDeltaC1C2} \alias{extractDeltaC1C2.PairedPSCBS} \alias{extractLocusLevelC1C2} \alias{extractLocusLevelC1C2.PairedPSCBS} \alias{extractLocusLevelTCN} \alias{extractLocusLevelTCN.PairedPSCBS} \alias{extractMinorMajorCNs} \alias{extractRegion} \alias{extractRegion.AbstractCBS} \alias{extractRegions} \alias{extractRegions.AbstractCBS} \alias{extractSegmentMeansByLocus} \alias{extractSegmentMeansByLocus.DNAcopy} \alias{extractTCNAndDHs} \alias{getCallStatistics} \alias{getCallStatisticsByArms} \alias{getCallStatisticsByArms.CBS} \alias{getChromosomeOffsets} \alias{getChromosomeRanges} \alias{getChromosomeRanges.CBS} \alias{getChromosomes} \alias{getChromosomes.DNAcopy} \alias{getFGA} \alias{getFGG} \alias{getFGL} \alias{getFractionOfGenomeAltered} \alias{getFractionOfGenomeGained} \alias{getFractionOfGenomeLost} \alias{getLocusData} \alias{getLocusData.CBS} \alias{getLocusData.PSCBS} \alias{getSampleName} \alias{getSampleNames} \alias{getSampleNames.DNAcopy} \alias{getSegments} \alias{getSegments.CBS} \alias{getSignalType} \alias{getSignalType.CBS} \alias{highlightArmCalls} \alias{highlightArmCalls.CBS} \alias{highlightCalls} \alias{highlightCalls.CBS} \alias{highlightLocusCalls} \alias{highlightLocusCalls.CBS} \alias{isWholeChromosomeGained} \alias{isWholeChromosomeGained.CBS} \alias{isWholeChromosomeLost} \alias{isWholeChromosomeLost.CBS} \alias{joinSegments} \alias{linesC1C2} \alias{linesC1C2.PairedPSCBS} \alias{linesDeltaC1C2} \alias{linesDeltaC1C2.PairedPSCBS} \alias{mergeNonCalledSegments} \alias{mergeTwoSegments} \alias{mergeTwoSegments.CBS} \alias{nbrOfAmplifications} \alias{nbrOfAmplifications.CBS} \alias{nbrOfChangePoints} \alias{nbrOfChromosomes} \alias{nbrOfGains} \alias{nbrOfGains.CBS} \alias{nbrOfLoci} \alias{nbrOfLoci.DNAcopy} \alias{nbrOfLosses} \alias{nbrOfLosses.CBS} \alias{nbrOfSamples} \alias{nbrOfSamples.DNAcopy} \alias{nbrOfSegments} \alias{nbrOfSegments.DNAcopy} \alias{plot.CBS} \alias{plot.PairedPSCBS} \alias{plotC1C2} \alias{plotC1C2.PairedPSCBS} \alias{plotDeltaC1C2} \alias{plotDeltaC1C2.PairedPSCBS} \alias{plotTracksManyChromosomes.CBS} \alias{pointsC1C2} \alias{pointsC1C2.PairedPSCBS} \alias{pointsDeltaC1C2} \alias{pointsDeltaC1C2.PairedPSCBS} \alias{postsegmentTCN} \alias{postsegmentTCN.PairedPSCBS} \alias{print.AbstractCBS} \alias{sampleName} \alias{sampleName<-} \alias{setLocusData} \alias{setSampleName} \alias{setSegments} \alias{signalType} \alias{signalType.CBS} \alias{signalType<-} \alias{signalType<-.CBS} \alias{subset.CBS} \alias{tileChromosomes} \alias{tileChromosomes.AbstractCBS} \alias{tileChromosomes.CBS} \alias{tileChromosomes.PairedPSCBS} \alias{writeLocusData} \alias{writeLocusData.CBS} \alias{writeSegments} \alias{extractSegments.AbstractCBS} \alias{extractSegment.AbstractCBS} \alias{extractSegment} \alias{extractSegments} \alias{extractSegments.CBS} \alias{extractSegments.PairedPSCBS} \alias{isSegmentSplitter} \alias{isSegmentSplitter.CBS} \alias{isSegmentSplitter.PSCBS} \alias{extractCNs} \alias{extractCNs.AbstractCBS} \alias{extractCNs.CBS} \alias{extractCNs.PairedPSCBS} \alias{extractTotalCNs} \alias{extractTotalCNs.CBS} \alias{getSegmentSizes} \alias{getSegmentSizes.AbstractCBS} \alias{getSegmentSizes.CBS} \alias{getSegmentSizes.PSCBS} \alias{sampleCNs} \alias{sampleCNs.AbstractCBS} \alias{mergeThreeSegments} \alias{callROH} \alias{callROHOneSegment} \alias{callROHOneSegment.PairedPSCBS} \alias{testROH} \alias{pruneBySdUndo} \alias{updateBoundaries} \alias{updateBoundaries.CBS} \alias{resegment} \alias{resegment.AbstractCBS} \alias{resegment.CBS} \alias{resegment.PairedPSCBS} \alias{hclustCNs} \alias{pruneByHClust} \alias{updateMeansTogether} \alias{updateMeans} \alias{drawChangePoints} \alias{drawChangePoints.AbstractCBS} \alias{drawKnownSegments} \alias{drawKnownSegments.AbstractCBS} \alias{drawChangePoints.CBS} \alias{drawChangePoints.PSCBS} \alias{drawChangePointsC1C2} \alias{drawChangePointsC1C2.PairedPSCBS} \alias{extractDhSegment} \alias{extractDhSegment.PairedPSCBS} \alias{callNTCN} \alias{callCopyNeutral} \alias{callCopyNeutralByTCNofAB} \alias{dropChangePoints} \alias{calcStatsForCopyNeutralABs} \alias{calcStatsForCopyNeutralABs.PairedPSCBS} \alias{callGainNeutralLoss} \alias{callGNL} \alias{renameChromosomes} \alias{renameChromosomes.AbstractCBS} \alias{report} \alias{writeSegments.DNAcopy} \alias{shiftTCN} \alias{shiftTCN.AbstractCBS} \alias{shiftTCN.CBS} \alias{shiftTCN.PairedPSCBS} \alias{getChromosomeOffsets.AbstractCBS} \alias{getChromosomeRanges.PairedPSCBS} \alias{getChromosomeRanges.AbstractCBS} \alias{seqOfSegmentsByDP} \alias{seqOfSegmentsByDP.AbstractCBS} \alias{seqOfSegmentsByDP.CBS} \alias{seqOfSegmentsByDP.PairedPSCBS} \alias{seqOfSegmentsByDP.matrix} \alias{getChromosomeOffsets.PairedPSCBS} \alias{getLocusSignalNames} \alias{getLocusSignalNames.AbstractCBS} \alias{getLocusSignalNames.CBS} \alias{getLocusSignalNames.PSCBS} \alias{getSegmentTrackPrefixes} \alias{getSegmentTrackPrefixes.AbstractCBS} \alias{getSegmentTrackPrefixes.CBS} \alias{getSegmentTrackPrefixes.PSCBS} \alias{pruneByDP} \alias{getMeanEstimators} \alias{getMeanEstimators.AbstractCBS} \alias{resegment.NonPairedPSCBS} \alias{setMeanEstimators} \alias{setMeanEstimators.AbstractCBS} \alias{resetSegments} \alias{getLocusData.NonPairedPSCBS} \alias{getLocusData.PairedPSCBS} \alias{plotTracks} \alias{plotTracks1} \alias{plotTracks2} \alias{plotTracksManyChromosomes} \alias{getSmoothLocusData} \alias{bootstrapSegmentsAndChangepoints} \alias{bootstrapSegmentsAndChangepoints.PairedPSCBS} \alias{getChangePoints} \alias{getChangePoints.AbstractCBS} \alias{getChangePoints.CBS} \alias{getChangePoints.PSCBS} \alias{clearBootstrapSummaries} \alias{clearBootstrapSummaries.PairedPSCBS} \alias{findBootstrapSummaries} \alias{findBootstrapSummaries.PairedPSCBS} \alias{hasBootstrapSummaries} \alias{hasBootstrapSummaries.PairedPSCBS} \alias{clearCalls} \alias{clearCalls.AbstractCBS} \alias{extractSegmentDataByLocus} \alias{extractSegmentDataByLocus.PairedPSCBS} \alias{updateMeansC1C2} \alias{updateMeansC1C2.PairedPSCBS} \alias{encodeCalls} \alias{encodeCalls.data.frame} \alias{callGLAO} \alias{callGLAO.CBS} \alias{unTumorBoost} \alias{unTumorBoost.PairedPSCBS} \alias{isLocallyPhased} \alias{isLocallyPhased.PSCBS} \description{ This page contains aliases for all "non-documented" objects that \code{R CMD check} detects in this package. Almost all of them are \emph{generic} functions that have specific document for the corresponding method coupled to a specific class. Other functions are re-defined by \code{setMethodS3()} to \emph{default} methods. Neither of these two classes are non-documented in reality. The rest are deprecated methods. } \author{Henrik Bengtsson} \keyword{documentation} \keyword{internal} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/extractSegmentMeansByLocus.CBS.Rd���������������������������������������������������������0000644�0001762�0000144�00000001671�15000477031�020060� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{extractSegmentMeansByLocus.CBS} \alias{extractSegmentMeansByLocus.CBS} \alias{CBS.extractSegmentMeansByLocus} \alias{extractSegmentMeansByLocus,CBS-method} \title{Extracts segments means at each locus} \description{ Extracts segments means at each locus. } \usage{ \method{extractSegmentMeansByLocus}{CBS}(fit, ...) } \arguments{ \item{...}{Arguments passed to \code{\link[PSCBS:getLocusData.CBS]{*getLocusData}()}.} } \value{ Returns a \code{\link[base]{numeric}} \code{\link[base]{vector}} of length \code{nbrOfLoci()}. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������PSCBS/man/callAB.PairedPSCBS.Rd���������������������������������������������������������������������0000644�0001762�0000144�00000005203�15000477031�015277� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callAB.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callAB.PairedPSCBS} \alias{callAB.PairedPSCBS} \alias{PairedPSCBS.callAB} \alias{callAB,PairedPSCBS-method} \alias{PairedPSCBS.callAllelicBalance} \alias{callAllelicBalance.PairedPSCBS} \alias{callAllelicBalance,PairedPSCBS-method} \title{Calls segments that are in allelic balance} \description{ Calls segments that are in allelic balance, i.e. that have equal minor and major copy numbers. } \usage{ \method{callAB}{PairedPSCBS}(fit, flavor=c("DeltaAB*"), ..., minSize=1, xorCalls=TRUE, force=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of call to use.} \item{...}{Additional arguments passed to the caller.} \item{minSize}{An optional \code{\link[base]{integer}} specifying the minimum number of data points in order to call a segments. If fewer data points, then the call is set to \code{\link[base]{NA}} regardless.} \item{xorCalls}{If \code{\link[base:logical]{TRUE}}, a region already called LOH, will for consistency never be called AB, resulting in either an AB call set to \code{\link[base:logical]{FALSE}} or \code{\link[base]{NA}} (as explained below).} \item{force}{If \code{\link[base:logical]{FALSE}}, and allelic-balance calls already exits, then nothing is done, otherwise the calls are done.} } \value{ Returns a \code{\link{PairedPSCBS}} object with allelic-balance calls. } \section{AB and LOH consistency}{ Biologically, a segment can not be both in allelic balance (AB) and in loss-of-heterozygosity (LOH) at the same time. To avoid reporting such inconsistencies, the LOH caller will, if argument \code{xorCalls=TRUE}, never report a segment to be in LOH if it is already called to be in AB. However, regardless of of the AB call, a segment is still always tested for LOH, to check weather the LOH caller is consistent with the AB caller or not. Thus, in order to distinguish the case where the AB caller and LOH caller agree from when they disagree, we report either (AB,LOH)=(TRUE,FALSE) or (TRUE,NA). The former is reported when they are consistent, and the latter when they are not, or when the AB caller could not call it. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:callAllelicBalanceByDH.PairedPSCBS]{*callAllelicBalanceByDH}()}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/dropRegions.AbstractCBS.Rd����������������������������������������������������������������0000644�0001762�0000144�00000004106�15000477031�016551� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{dropRegions.AbstractCBS} \alias{dropRegions.AbstractCBS} \alias{AbstractCBS.dropRegions} \alias{dropRegions,AbstractCBS-method} \alias{AbstractCBS.dropRegion} \alias{dropRegion.AbstractCBS} \alias{dropRegion,AbstractCBS-method} \title{Drops chromosomal regions (a connected set of segments)} \description{ Drops chromosomal regions (a connected set of segments) each of a certain size (number of segments). \emph{None of the statistics are recalculated}. } \usage{ \method{dropRegions}{AbstractCBS}(this, regions, H=1, ..., asMissing=FALSE, verbose=FALSE) } \arguments{ \item{regions}{An \code{\link[base]{integer}} \code{\link[base]{vector}} of length R specifying the indices of the left most segment in each of the R regions to be dropped.} \item{H}{A non-negative \code{\link[base]{integer}} specifying the size of each region, i.e. the number of segments per region.} \item{...}{Additional arguments passed to \code{\link[PSCBS:extractRegions.AbstractCBS]{*extractRegions}()}.} \item{asMissing}{If \code{\link[base:logical]{TRUE}}, dropped segments are replaced by missing values, otherwise they are truly dropped.} \item{verbose}{A \code{\link[base]{logical}} or a \code{\link[R.utils]{Verbose}} object.} } \value{ Returns an \code{\link{AbstractCBS}} object of the same class with (at most) R*H segments dropped. If some regions overlap (share segments), then fewer than R*H segments are dropped. } \author{Henrik Bengtsson} \seealso{ Internally \code{\link[PSCBS:extractRegions.AbstractCBS]{*extractRegions}()} is used. See also \code{\link[PSCBS:dropChangePoint.AbstractCBS]{*dropChangePoint}()} and \code{\link[PSCBS:mergeTwoSegments.AbstractCBS]{*mergeTwoSegments}()}. For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/segmentByPairedPSCBS.Rd�������������������������������������������������������������������0000644�0001762�0000144�00000026077�15000477031�016054� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % segmentByPairedPSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{segmentByPairedPSCBS} \alias{segmentByPairedPSCBS.default} \alias{segmentByPairedPSCBS} \alias{segmentByPairedPSCBS.data.frame} \alias{segmentByPairedPSCBS.PairedPSCBS} \alias{segmentByPairedPSCBS} \title{Segment total copy numbers and allele B fractions using the Paired PSCBS method} \description{ Segment total copy numbers and allele B fractions using the Paired PSCBS method [1]. This method requires matched normals. This is a low-level segmentation method. It is intended to be applied to one tumor-normal sample at the time. } \usage{ \method{segmentByPairedPSCBS}{default}(CT, thetaT=NULL, thetaN=NULL, betaT=NULL, betaN=NULL, muN=NULL, rho=NULL, chromosome=0, x=NULL, alphaTCN=0.009, alphaDH=0.001, undoTCN=0, undoDH=0, ..., avgTCN=c("mean", "median"), avgDH=c("mean", "median"), flavor=c("tcn&dh", "tcn,dh", "sqrt(tcn),dh", "sqrt(tcn)&dh", "tcn"), tbn=is.null(rho), joinSegments=TRUE, knownSegments=NULL, dropMissingCT=TRUE, seed=NULL, verbose=FALSE, preserveScale=FALSE) } \arguments{ \item{CT}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J tumor total copy number (TCN) ratios in [0,+\code{\link[base:is.finite]{Inf}}) (due to noise, small negative values are also allowed). The TCN ratios are typically scaled such that copy-neutral diploid loci have a mean of two.} \item{thetaT, thetaN}{(alternative) As an alternative to specifying tumor TCN \emph{ratios} relative to the match normal by argument \code{CT}, on may specify total tumor and normal signals seperately, in which case the TCN ratios \code{CT} are calculated as \eqn{CT = 2*thetaT/thetaN}.} \item{betaT}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J tumor allele B fractions (BAFs) in [0,1] (due to noise, values may be slightly outside as well) or \code{\link[base]{NA}} for non-polymorphic loci.} \item{betaN}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J matched normal BAFs in [0,1] (due to noise, values may be slightly outside as well) or \code{\link[base]{NA}} for non-polymorphic loci.} \item{muN}{An optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genotype calls in \{0,1/2,1\} for AA, AB, and BB, respectively, and \code{\link[base]{NA}} for non-polymorphic loci. If not given, they are estimated from the normal BAFs using \code{\link[aroma.light]{callNaiveGenotypes}} as described in [2].} \item{rho}{(alternative to \code{betaT} and \code{betaN}/\code{muN}) A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J decrease-of-heterozygosity signals (DHs) in [0,1] (due to noise, values may be slightly larger than one as well). By definition, DH should be \code{\link[base]{NA}} for homozygous loci and for non-polymorphic loci.} \item{chromosome}{(Optional) An \code{\link[base]{integer}} scalar (or a \code{\link[base]{vector}} of length J), which can be used to specify which chromosome each locus belongs to in case multiple chromosomes are segments. This argument is also used for annotation purposes.} \item{x}{Optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genomic locations. If \code{\link[base]{NULL}}, index locations \code{1:J} are used.} \item{alphaTCN, alphaDH}{The significance levels for segmenting total copy numbers (TCNs) and decrease-in-heterozygosity signals (DHs), respectively.} \item{undoTCN, undoDH}{Non-negative \code{\link[base]{numeric}}s. If greater than 0, then a cleanup of segmentions post segmentation is done. See argument \code{undo} of \code{\link{segmentByCBS}}() for more details.} \item{avgTCN, avgDH}{A \code{\link[base]{character}} string specifying how to calculating segment mean levels \emph{after} change points have been identified.} \item{...}{Additional arguments passed to \code{\link{segmentByCBS}}().} \item{flavor}{A \code{\link[base]{character}} specifying what type of segmentation and calling algorithm to be used.} \item{tbn}{If \code{\link[base:logical]{TRUE}}, \code{betaT} is normalized before segmentation using the TumorBoost method [2], otherwise not.} \item{joinSegments}{If \code{\link[base:logical]{TRUE}}, there are no gaps between neighboring segments. If \code{\link[base:logical]{FALSE}}, the boundaries of a segment are defined by the support that the loci in the segments provides, i.e. there exist a locus at each end point of each segment. This also means that there is a gap between any neighboring segments, unless the change point is in the middle of multiple loci with the same position. The latter is what \code{DNAcopy::segment()} returns. } \item{knownSegments}{Optional \code{\link[base]{data.frame}} specifying \emph{non-overlapping} known segments. These segments must not share loci. See \code{\link{findLargeGaps}}() and \code{\link{gapsToSegments}}().} \item{dropMissingCT}{If \code{\link[base:logical]{TRUE}}, loci for which 'CT' is missing are dropped, otherwise not.} \item{seed}{An (optional) \code{\link[base]{integer}} specifying the random seed to be set before calling the segmentation method. The random seed is set to its original state when exiting. If \code{\link[base]{NULL}}, it is not set.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} \item{preserveScale}{\emph{Defunct - gives an error is specified.}} } \value{ Returns the segmentation results as a \code{\link{PairedPSCBS}} object. } \details{ Internally \code{\link{segmentByCBS}}() is used for segmentation. The Paired PSCBS segmentation method does \emph{not} support weights. } \section{Reproducibility}{ The "DNAcopy::segment" implementation of CBS uses approximation through random sampling for some estimates. Because of this, repeated calls using the same signals may result in slightly different results, unless the random seed is set/fixed. } \section{Whole-genome segmentation is preferred}{ Although it is possible to segment each chromosome independently using Paired PSCBS, we strongly recommend to segment whole-genome (TCN,BAF) data at once. The reason for this is that downstream CN-state calling methods, such as the AB and the LOH callers, performs much better on whole-genome data. In fact, they may fail to provide valid calls if done chromosome by chromosome. } \section{Missing and non-finite values}{ The total copy number signals as well as any optional positions must not contain missing values, i.e. \code{\link[base]{NA}}s or \code{\link[base:is.finite]{NaN}}s. If there are any, an informative error is thrown. Allele B fractions may contain missing values, because such are interpreted as representing non-polymorphic loci. None of the input signals may have infinite values, i.e. -\code{\link[base:is.finite]{Inf}} or +\code{\link[base:is.finite]{Inf}}. If so, an informative error is thrown. } \section{Paired PSCBS with only genotypes}{ If allele B fractions for the matched normal (\code{betaN}) are not available, but genotypes (\code{muN}) are, then it is possible to run a version of Paired PSCBS where TumorBoost normalization of the tumor allele B fractions is skipped. In order for this to work, argument \code{tbn} must be set to \code{\link[base:logical]{FALSE}}. } \examples{ verbose <- R.utils::Arguments$getVerbose(-10*interactive(), timestamp=TRUE) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=10),] str(dataS) R.oo::attachLocally(dataS) # Paired PSCBS segmentation fit <- segmentByPairedPSCBS(CT, betaT=betaT, betaN=betaN, chromosome=chromosome, x=x, seed=0xBEEF, verbose=verbose) print(fit) # Plot results plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=100, verbose=verbose) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance (AB) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in DH for calling AB # (which be done by default by the caller, if skipped here) deltaAB <- estimateDeltaAB(fit, flavor="qq(DH)", verbose=verbose) print(deltaAB) ## [1] 0.1657131 fit <- callAB(fit, delta=deltaAB, verbose=verbose) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaAB == deltaAB) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in loss-of-heterozygosity (LOH) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in C1 for calling LOH # (which be done by default by the caller, if skipped here) deltaLOH <- estimateDeltaLOH(fit, flavor="minC1|nonAB", verbose=verbose) print(deltaLOH) ## [1] 0.625175 fit <- callLOH(fit, delta=deltaLOH, verbose=verbose) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaLOH == deltaLOH) } \author{Henrik Bengtsson} \references{ [1] A.B. Olshen, H. Bengtsson, P. Neuvial, P.T. Spellman, R.A. Olshen, V.E. Seshan, \emph{Parent-specific copy number in paired tumor-normal studies using circular binary segmentation}, Bioinformatics, 2011 \cr [2] H. Bengtsson, P. Neuvial and T.P. Speed, \emph{TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays}, BMC Bioinformatics, 2010 \cr } \seealso{ Internally, \code{\link[aroma.light]{callNaiveGenotypes}} is used to call naive genotypes, \code{\link[aroma.light]{normalizeTumorBoost}} is used for TumorBoost normalization, and \code{\link{segmentByCBS}}() is used to segment TCN and DH separately. To segment tumor total copy numbers and allele B fractions \emph{without} a matched normal, see \code{\link{segmentByNonPairedPSCBS}}(). To segment total copy-numbers, or any other unimodal signals, see \code{\link{segmentByCBS}}(). } \keyword{IO} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/hclustCNs.AbstractCBS.Rd������������������������������������������������������������������0000644�0001762�0000144�00000002357�15000477031�016172� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.HCLUST.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{hclustCNs.AbstractCBS} \alias{hclustCNs.AbstractCBS} \alias{AbstractCBS.hclustCNs} \alias{hclustCNs,AbstractCBS-method} \title{Performs a hierarchical clustering of the CN mean levels} \description{ Performs a hierarchical clustering of the CN mean levels. } \usage{ \method{hclustCNs}{AbstractCBS}(fit, size=NULL, distMethod="euclidean", hclustMethod="ward.D", ..., verbose=FALSE) } \arguments{ \item{size}{Argument passed to \code{\link[PSCBS:sampleCNs.AbstractCBS]{*sampleCNs}()}.} \item{distMethod, hclustMethod}{Argument \code{method} for \code{\link[stats]{dist}} and "stats::hclust", respectively.} \item{...}{Not used.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{hclust} object as returned by \code{\link[stats]{hclust}}. } \author{Henrik Bengtsson} \seealso{ This method is utilized by \code{\link[PSCBS:pruneByHClust.AbstractCBS]{*pruneByHClust}()}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/findNeutralCopyNumberState.Rd�������������������������������������������������������������0000644�0001762�0000144�00000003241�15000477031�017443� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % findNeutralCopyNumberState.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{findNeutralCopyNumberState} \alias{findNeutralCopyNumberState.default} \alias{findNeutralCopyNumberState} \title{Call segments to be copy neutral based on allelic imbalance calls and total copy number estimates} \description{ Call segments to be copy neutral based on allelic imbalance calls and total copy number estimates. } \usage{ \method{findNeutralCopyNumberState}{default}(C, isAI, weights=NULL, ..., minDensity=1e-10, flavor=c("firstPeak", "maxPeak"), verbose=FALSE) } \arguments{ \item{C}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of region-level total copy number estimates.} \item{isAI}{A \code{\link[base]{logical}} \code{\link[base]{vector}} of "allelic imbalance" calls.} \item{weights}{An optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of non-negative weights.} \item{...}{Further arguments to be passed to the density estimation function.} \item{minDensity}{A \code{\link[base]{numeric}} value, below which density peaks are discarded.} \item{flavor}{A \code{\link[base]{character}} string specifying how to identify the mode of the AB segments.} \item{verbose}{If \code{\link[base:logical]{TRUE}}, extra information is output.} } \value{ A \code{\link[base]{logical}} \code{\link[base]{vector}} of "neutral copy number state" calls. } \author{Pierre Neuvial, Henrik Bengtsson} \keyword{internal} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/extractTCNAndDHs.PairedPSCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000001704�15000477031�017224� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{extractTCNAndDHs.PairedPSCBS} \alias{extractTCNAndDHs.PairedPSCBS} \alias{PairedPSCBS.extractTCNAndDHs} \alias{extractTCNAndDHs,PairedPSCBS-method} \title{Extract TCN and DH mean levels per segment} \description{ Extract TCN and DH mean levels per segment. } \usage{ \method{extractTCNAndDHs}{PairedPSCBS}(fit, ...) } \arguments{ \item{...}{Arguments passed to \code{getSegments()}.} } \value{ Returns a \code{\link[base]{data.frame}}. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:extractMinorMajorCNs.PairedPSCBS]{*extractMinorMajorCNs}()}. For more information see \code{\link{PairedPSCBS}}. } \keyword{internal} \keyword{methods} ������������������������������������������������������������PSCBS/man/callAmplifications.CBS.Rd�����������������������������������������������������������������0000644�0001762�0000144�00000003602�15000477031�016370� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callAmplifications.CBS} \alias{callAmplifications.CBS} \alias{CBS.callAmplifications} \alias{callAmplifications,CBS-method} \title{Calls (focal) amplifications} \description{ Calls (focal) amplifications. } \usage{ \method{callAmplifications}{CBS}(fit, adjust=1, maxLength=2e+07, method=c("ucsf-exp"), ..., verbose=FALSE) } \arguments{ \item{adjust}{A positive scale factor adjusting the sensitivity of the caller, where a value less (greater) than 1.0 makes the caller less (more) sensitive.} \item{maxLength}{A \code{\link[base]{double}} scalar specifying the maximum length of a segment in order for it to be considered a focal amplification.} \item{method}{A \code{\link[base]{character}} string specifying the calling algorithm to use.} \item{...}{Additional/optional arguments used to override the default parameters used by the caller.} \item{verbose}{\code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link[PSCBS]{CBS}} object where \code{\link[base]{logical}} column 'amplificationCall' has been appended to the segmentation table. } \section{The UCSF caller}{ If \code{method == "ucsf-exp"}, then segments are called using [1], i.e. a segment is called an amplification if ... } \author{Henrik Bengtsson} \references{ [1] Fridlyand et al. \emph{Breast tumor copy number aberration phenotypes and genomic instability}, BMC Cancer, 2006. \cr } \seealso{ \code{\link[PSCBS:callGainsAndLosses.CBS]{*callGainsAndLosses}()}. \code{\link[PSCBS:callOutliers.CBS]{*callOutliers}()}. For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ������������������������������������������������������������������������������������������������������������������������������PSCBS/man/installDNAcopy.Rd�������������������������������������������������������������������������0000644�0001762�0000144�00000002176�15000477031�015055� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % installDNAcopy.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{installDNAcopy} \alias{installDNAcopy.default} \alias{installDNAcopy} \title{Install the DNAcopy package} \usage{ \method{installDNAcopy}{default}(..., force=FALSE) } \description{ Install the DNAcopy package, if missing. } \arguments{ \item{...}{Arguments passed to the install function.} \item{force}{If \code{\link[base:logical]{FALSE}} and the \pkg{DNAcopy} package is already installed, then it will not be re-install. If \code{\link[base:logical]{TRUE}}, it will be installed.} } \value{ Returns nothing. } \details{ This function is will download and call the \code{biocLite()} installation function from the Bioconductor Project website. This function will also make sure that \pkg{DNAcopy} is loaded so that it is reported by \code{\link[utils]{sessionInfo}}. } \author{Henrik Bengtsson} \keyword{internal} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getBootstrapLocusSets.PairedPSCBS.Rd������������������������������������������������������0000644�0001762�0000144�00000003352�15000477031�020506� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.BOOT.sets.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getBootstrapLocusSets.PairedPSCBS} \alias{getBootstrapLocusSets.PairedPSCBS} \alias{PairedPSCBS.getBootstrapLocusSets} \alias{getBootstrapLocusSets,PairedPSCBS-method} \alias{getBootstrapLocusSets} \title{Generates original and bootstrapped segment-specific index sets} \description{ Generates original and bootstrapped segment-specific index sets, which can be used to calculate various bootstrap summaries, e.g. segment mean levels. } \usage{ \method{getBootstrapLocusSets}{PairedPSCBS}(fit, B=1000L, by=c("betaTN", "betaT"), seed=NULL, verbose=FALSE, .validate=FALSE, ...) } \arguments{ \item{B}{A non-negative \code{\link[base]{integer}} specifying the number of bootstrap samples.} \item{by}{Should \code{betaTN} or \code{betaT} be used?} \item{seed}{An (optional) \code{\link[base]{integer}} specifying the random seed to be set before sampling indices. The random seed is set to its original state when exiting. If \code{\link[base]{NULL}}, it is not set.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} \item{.validate}{If \code{\link[base:logical]{TRUE}}, additional sanity checks are performed to validate the correctness. This is only needed for troubleshooting if it is suspected there is a bug.} \item{...}{Not used.} } \value{ Returns a \code{\link[base]{list}}. } \author{Henrik Bengtsson} \seealso{ This is used internally by various bootstrap methods. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/dropChangePoints.AbstractCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000002763�15000477031�017534� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{dropChangePoints.AbstractCBS} \alias{dropChangePoints.AbstractCBS} \alias{AbstractCBS.dropChangePoints} \alias{dropChangePoints,AbstractCBS-method} \title{Drops zero or more change points} \description{ Drops zero or more change points, which is done by dropping one change point at the time using \code{\link[PSCBS:dropChangePoint.AbstractCBS]{*dropChangePoint}()} and recalculating the segment statistics at the end. \emph{NOTE: This method only works if there is only one chromosome.} } \usage{ \method{dropChangePoints}{AbstractCBS}(fit, idxs, update=TRUE, ...) } \arguments{ \item{idxs}{An \code{\link[base]{integer}} \code{\link[base]{vector}} specifying the change points to be dropped.} \item{update}{If \code{\link[base:logical]{TRUE}}, segment statistics are updated.} \item{...}{Other arguments passed to \code{\link[PSCBS:dropChangePoint.AbstractCBS]{*dropChangePoint}()} and \code{\link[PSCBS:updateMeans.AbstractCBS]{*updateMeans}()}.} } \value{ Returns an \code{\link{AbstractCBS}} of the same class with \code{length(idxs)} segments. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} �������������PSCBS/man/mergeNonCalledSegments.CBS.Rd�������������������������������������������������������������0000644�0001762�0000144�00000001650�15000477031�017160� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{mergeNonCalledSegments.CBS} \alias{mergeNonCalledSegments.CBS} \alias{CBS.mergeNonCalledSegments} \alias{mergeNonCalledSegments,CBS-method} \title{Merge neighboring segments that are not called} \description{ Merge neighboring segments that are not called } \usage{ \method{mergeNonCalledSegments}{CBS}(fit, ..., verbose=FALSE) } \arguments{ \item{...}{Not used.} \item{verbose}{\code{\link[R.utils]{Verbose}}.} } \value{ Returns an object of the same class with the same of fewer number of segments. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������PSCBS/man/resetSegments.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000002123�15000477031�017103� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{resetSegments.AbstractCBS} \alias{resetSegments.AbstractCBS} \alias{AbstractCBS.resetSegments} \alias{resetSegments,AbstractCBS-method} \title{Reset the segments} \description{ Reset the segments. More precisely, it removes columns in the segmentation result table that have been added by methods after the actual segmentation method, e.g. bootstrap estimated mean level quantiles and various calls. It leave the basic segmentation results untouched, i.e. the partitioning and the segment means. } \usage{ \method{resetSegments}{AbstractCBS}(fit, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns an object if the same class as the input result. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getSmoothLocusData.CBS.Rd�����������������������������������������������������������������0000644�0001762�0000144�00000002107�15000477031�016342� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.SMOOTH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getSmoothLocusData.CBS} \alias{getSmoothLocusData.CBS} \alias{CBS.getSmoothLocusData} \alias{getSmoothLocusData,CBS-method} \title{Gets smoothed locus-level data} \description{ Gets smoothed locus-level data. } \usage{ \method{getSmoothLocusData}{CBS}(fit, by, ...) } \arguments{ \item{fit}{An \code{\link{CBS}} object.} \item{by}{A \code{\link[base]{numeric}} scalar specifying the bin size.} \item{...}{Not used.} } \value{ Returns a \code{\link[base]{data.frame}} where the first three columns are 'chromosome', 'x' (position), and 'count' (number of loci average over for the given bin), and the remaining ones are the smoothed locus-level data. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/AbstractCBS.Rd����������������������������������������������������������������������������0000644�0001762�0000144�00000006072�15000477031�014263� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{AbstractCBS} \docType{class} \alias{AbstractCBS} \title{The AbstractCBS class} \description{ Package: PSCBS \cr \bold{Class AbstractCBS}\cr \code{list}\cr \code{~~|}\cr \code{~~+--}\emph{\code{AbstractCBS}}\cr \bold{Directly known subclasses:}\cr \emph{\link[PSCBS]{CBS}}, \emph{\link[PSCBS]{NonPairedPSCBS}}, \emph{\link[PSCBS]{PSCBS}}, \emph{\link[PSCBS]{PairedPSCBS}}\cr public abstract class \bold{AbstractCBS}\cr extends list\cr All CBS-style segmentation results extend this class, e.g. \code{\link{CBS}} and \code{\link{PairedPSCBS}}. } \usage{ AbstractCBS(fit=list(), sampleName=fit$sampleName, ...) } \arguments{ \item{fit}{A \code{\link[base]{list}} structure containing the segmentation results.} \item{sampleName}{A \code{\link[base]{character}} string.} \item{...}{Not used.} } \section{Fields and Methods}{ \bold{Methods:}\cr \tabular{rll}{ \tab \code{adjustPloidyScale} \tab -\cr \tab \code{extractCNs} \tab -\cr \tab \code{getChangePoints} \tab -\cr \tab \code{\link[PSCBS:getChromosomes.AbstractCBS]{getChromosomes}} \tab Gets the set of chromosomes.\cr \tab \code{\link[PSCBS:getLocusData.AbstractCBS]{getLocusData}} \tab Gets the locus-level data.\cr \tab \code{getSegmentSizes} \tab -\cr \tab \code{\link[PSCBS:getSegments.AbstractCBS]{getSegments}} \tab Gets the segments.\cr \tab \code{\link[PSCBS:mergeThreeSegments.AbstractCBS]{mergeThreeSegments}} \tab Merge a segment and its two flanking segments.\cr \tab \code{\link[PSCBS:nbrOfChangePoints.AbstractCBS]{nbrOfChangePoints}} \tab Gets the number of change points.\cr \tab \code{\link[PSCBS:nbrOfChromosomes.AbstractCBS]{nbrOfChromosomes}} \tab Gets the number of chromosomes.\cr \tab \code{\link[PSCBS:nbrOfLoci.AbstractCBS]{nbrOfLoci}} \tab Gets the number of loci.\cr \tab \code{\link[PSCBS:nbrOfSegments.AbstractCBS]{nbrOfSegments}} \tab Gets the number of segments.\cr \tab \code{\link[PSCBS:normalizeTotalCNs.AbstractCBS]{normalizeTotalCNs}} \tab Normalizes copy numbers such that the whole-genome average total copy number is two.\cr \tab \code{\link[PSCBS:ploidy.AbstractCBS]{ploidy}} \tab Gets and sets ploidy.\cr \tab \code{ploidy<-} \tab -\cr \tab \code{\link[PSCBS:plotTracks.AbstractCBS]{plotTracks}} \tab Plots the segmentation result along the genome.\cr \tab \code{sampleCNs} \tab -\cr \tab \code{writeWIG} \tab -\cr } \bold{Methods inherited from list}:\cr Ops,nonStructure,vector-method, Ops,structure,vector-method, Ops,vector,nonStructure-method, Ops,vector,structure-method, all.equal, as.data.frame, attachLocally, averageQuantile, callHooks, coerce,ANY,list-method, normalizeAverage, normalizeDifferencesToAverage, normalizeQuantileRank, normalizeQuantileSpline, plotDensity, relist, reset, type.convert, within } \author{Henrik Bengtsson} \keyword{classes} \keyword{internal} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/PSCBS.Rd����������������������������������������������������������������������������������0000644�0001762�0000144�00000005211�15000477031�013034� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{PSCBS} \docType{class} \alias{PSCBS} \title{The PSCBS class} \description{ Package: PSCBS \cr \bold{Class PSCBS}\cr \code{list}\cr \code{~~|}\cr \code{~~+--}\code{\link[PSCBS]{AbstractCBS}}\cr \code{~~~~~~~|}\cr \code{~~~~~~~+--}\emph{\code{PSCBS}}\cr \bold{Directly known subclasses:}\cr \emph{\link[PSCBS]{NonPairedPSCBS}}, \emph{\link[PSCBS]{PairedPSCBS}}\cr public abstract class \bold{PSCBS}\cr extends \emph{\link[PSCBS]{AbstractCBS}}\cr A PSCBS is an object containing results from parent-specific copy-number (PSCN) segmentation. } \usage{PSCBS(fit=list(), ...)} \arguments{ \item{fit}{A \code{\link[base]{list}} structure containing the PSCN segmentation results.} \item{...}{Not used.} } \section{Fields and Methods}{ \bold{Methods:}\cr \tabular{rll}{ \tab \code{c} \tab -\cr \tab \code{isLocallyPhased} \tab -\cr \tab \code{normalizeTotalCNs} \tab -\cr \tab \code{\link[PSCBS:writeSegments.PSCBS]{writeSegments}} \tab Writes the table of segments to file.\cr } \bold{Methods inherited from AbstractCBS}:\cr adjustPloidyScale, all.equal, as.data.frame, clearCalls, drawChangePoints, drawKnownSegments, dropChangePoint, dropChangePoints, dropRegion, dropRegions, extractCNs, extractChromosome, extractChromosomes, extractRegions, extractSegments, extractWIG, getChangePoints, getChromosomeOffsets, getChromosomeRanges, getChromosomes, getLocusData, getLocusSignalNames, getMeanEstimators, getSampleName, getSegmentSizes, getSegmentTrackPrefixes, getSegments, mergeThreeSegments, mergeTwoSegments, nbrOfChangePoints, nbrOfChromosomes, nbrOfLoci, nbrOfSegments, normalizeTotalCNs, ploidy, ploidy<-, plotTracks, print, pruneByDP, pruneByHClust, renameChromosomes, report, resegment, resetSegments, sampleCNs, sampleName, sampleName<-, seqOfSegmentsByDP, setLocusData, setMeanEstimators, setPloidy, setSampleName, setSegments, shiftTCN, tileChromosomes, updateMeans, writeWIG \bold{Methods inherited from list}:\cr Ops,nonStructure,vector-method, Ops,structure,vector-method, Ops,vector,nonStructure-method, Ops,vector,structure-method, all.equal, as.data.frame, attachLocally, averageQuantile, callHooks, coerce,ANY,list-method, normalizeAverage, normalizeDifferencesToAverage, normalizeQuantileRank, normalizeQuantileSpline, plotDensity, relist, reset, type.convert, within } \author{Henrik Bengtsson} \seealso{ \code{\link{PairedPSCBS}}. } \keyword{classes} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/joinSegments.CBS.Rd�����������������������������������������������������������������������0000644�0001762�0000144�00000002341�15000477031�015236� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.joinSegments.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{joinSegments.CBS} \alias{joinSegments.CBS} \alias{CBS.joinSegments} \alias{joinSegments,CBS-method} \title{Joins neighboring segments such that there is no gap in between them} \description{ Joins neighboring segments such that there is no gap in between them. For instance, consider two neighboring segments [x1,x2] and [x3,x4] with x1 < x2 < x3 < x4. After join the segments, they are [x1,x23] and [x23,x4] where x23 = (x2 + x3)/2. } \usage{ \method{joinSegments}{CBS}(fit, range=NULL, verbose=FALSE, ...) } \arguments{ \item{range}{(optional) A \code{\link[base]{numeric}} \code{\link[base]{vector}} of length two.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} \item{...}{Not used.} } \value{ Returns an updated \code{\link{CBS}} object. } \details{ This function assumes only chromosome exists. If more, an error will be thrown. } \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} \keyword{IO} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/extractMinorMajorCNs.PairedPSCBS.Rd�������������������������������������������������������0000644�0001762�0000144�00000002071�15000477031�020235� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{extractMinorMajorCNs.PairedPSCBS} \alias{extractMinorMajorCNs.PairedPSCBS} \alias{PairedPSCBS.extractMinorMajorCNs} \alias{extractMinorMajorCNs,PairedPSCBS-method} \alias{PairedPSCBS.extractC1C2} \alias{extractC1C2.PairedPSCBS} \alias{extractC1C2,PairedPSCBS-method} \title{Extract minor and major copy-number mean levels per segment} \description{ Extract minor and major copy-number mean levels per segment. } \usage{ \method{extractMinorMajorCNs}{PairedPSCBS}(fit, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns a \code{\link[base]{data.frame}}. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:extractTCNAndDHs.PairedPSCBS]{*extractTCNAndDHs}()} For more information see \code{\link{PairedPSCBS}}. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/as.data.frame.CBS.Rd����������������������������������������������������������������������0000644�0001762�0000144�00000001531�15000477031�015175� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{as.data.frame.CBS} \alias{as.data.frame.CBS} \alias{CBS.as.data.frame} \alias{as.data.frame,CBS-method} \title{Gets the table of segments} \description{ Gets the table of segments. } \usage{ \method{as.data.frame}{CBS}(x, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns a \code{\link[base]{data.frame}}, where each row corresponds to a unique segment. } \author{Henrik Bengtsson} \seealso{ Utilizes \code{\link[PSCBS:getSegments.CBS]{*getSegments}()}. For more information see \code{\link{CBS}}.. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getSegments.AbstractCBS.Rd����������������������������������������������������������������0000644�0001762�0000144�00000001736�15000477031�016551� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getSegments.AbstractCBS} \alias{getSegments.AbstractCBS} \alias{AbstractCBS.getSegments} \alias{getSegments,AbstractCBS-method} \alias{AbstractCBS.setSegments} \alias{setSegments.AbstractCBS} \alias{setSegments,AbstractCBS-method} \alias{setSegments.AbstractCBS} \title{Gets the segments} \description{ Gets the segments. } \usage{ \method{getSegments}{AbstractCBS}(...) } \arguments{ \item{...}{Not used.} } \value{ Returns a SxK \code{\link[base]{data.frame}}, where S in the number of segments, and K is the number of segment-specific fields. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ����������������������������������PSCBS/man/weightedQuantile.Rd�����������������������������������������������������������������������0000644�0001762�0000144�00000003715�15000477031�015474� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % weightedQuantile.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{weightedQuantile} \alias{weightedQuantile.default} \alias{weightedQuantile} \title{Weighted Quantile Value} \usage{ \method{weightedQuantile}{default}(x, w, probs=c(0, 0.25, 0.5, 0.75, 1), na.rm=TRUE, method=c("wtd.quantile"), ...) } \description{ Computes a weighted quantile of a numeric vector. } \arguments{ \item{x}{a \code{\link[base]{numeric}} \code{\link[base]{vector}} containing the values whose weighted quantile is to be computed.} \item{w}{a numeric \code{\link[base]{vector}} of weights the same length as \code{x} giving the weights to use for each element of \code{x}. Negative weights are treated as zero weights. Default value is equal weight to all values.} \item{probs}{a \code{\link[base]{numeric}} \code{\link[base]{vector}} of quantiles in [0,1] to be retrieved.} \item{na.rm}{a \code{\link[base]{logical}} value indicating whether \code{\link[base]{NA}} values in \code{x} should be stripped before the computation proceeds, or not.} \item{method}{If \code{"wtd.quantile"}, then an internal copy of \code{Hmisc::wtd.quantile()} is used. No other methods are currently supported.} \item{...}{Additional arguments passed to the estimator.} } \value{ Returns the weighted quantile. } \author{Henrik Bengtsson} \seealso{ Internally the following functions may be used: \code{\link[stats]{quantile}} (if no weights are specified), or an internal copy of \code{Hmisc::wtd.quantile()}. For a weighted median estimator, \code{\link[matrixStats]{weightedMedian}} of the \pkg{matrixStats} package. } \keyword{univar} \keyword{robust} \keyword{internal} ���������������������������������������������������PSCBS/man/exampleData.Rd����������������������������������������������������������������������������0000644�0001762�0000144�00000001400�15000477031�014403� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % exampleData.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{exampleData} \alias{exampleData.default} \alias{exampleData} \title{Gets an example data set} \description{ Gets an example data set. } \usage{ \method{exampleData}{default}(name=c("paired.chr01"), ...) } \arguments{ \item{name}{A \code{\link[base]{character}} string specifying the name of the data set.} \item{...}{Not used.} } \value{ Returns \code{\link[base]{data.frame}}. } \author{Henrik Bengtsson} \keyword{IO} \keyword{data} \keyword{internal} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateKappa.PairedPSCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000002417�15000477031�016755� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateKappa.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateKappa.PairedPSCBS} \alias{estimateKappa.PairedPSCBS} \alias{PairedPSCBS.estimateKappa} \alias{estimateKappa,PairedPSCBS-method} \title{Estimate global background in segmented copy numbers} \description{ Estimate global background in segmented copy numbers. The global background, here called \eqn{\kappa}, may have multiple origins where normal contamination is one, but not necessarily the only one. } \usage{ \method{estimateKappa}{PairedPSCBS}(this, flavor=c("density(C1)"), ...) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of estimator to use.} \item{...}{Additional arguments passed to the estimator.} } \value{ Returns the background estimate as a \code{\link[base]{numeric}} scalar. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:estimateKappaByC1Density.PairedPSCBS]{*estimateKappaByC1Density}()}. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/nbrOfLoci.AbstractCBS.Rd������������������������������������������������������������������0000644�0001762�0000144�00000001547�15000477031�016141� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{nbrOfLoci.AbstractCBS} \alias{nbrOfLoci.AbstractCBS} \alias{AbstractCBS.nbrOfLoci} \alias{nbrOfLoci,AbstractCBS-method} \title{Gets the number of loci} \description{ Gets the number of loci. } \usage{ \method{nbrOfLoci}{AbstractCBS}(fit, splitters=FALSE, ...) } \arguments{ \item{splitters, ...}{Arguments passed to \code{\link[PSCBS:getLocusData.AbstractCBS]{*getLocusData}()}.} } \value{ Returns an \code{\link[base]{integer}}. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateDeltaLOHByMinC1ForNonAB.PairedPSCBS.Rd��������������������������������������������0000644�0001762�0000144�00000004460�15000477031�021765� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateDeltaLOH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateDeltaLOHByMinC1ForNonAB.PairedPSCBS} \alias{estimateDeltaLOHByMinC1ForNonAB.PairedPSCBS} \alias{PairedPSCBS.estimateDeltaLOHByMinC1ForNonAB} \alias{estimateDeltaLOHByMinC1ForNonAB,PairedPSCBS-method} \title{Estimate a threshold for calling LOH from DH} \description{ Estimate a threshold for calling LOH from DH based on the location of guessed C1=0 and C1=1 peaks. } \usage{ \method{estimateDeltaLOHByMinC1ForNonAB}{PairedPSCBS}(this, midpoint=1/2, maxC=3 * (ploidy(this)/2), ..., verbose=FALSE) } \arguments{ \item{midpoint}{A \code{\link[base]{numeric}} scalar in [0,1] specifying the relative position of the midpoint between the estimated locations of C1=0 and C1=1 mean parameters.} \item{maxC}{Maximum total copy number of a segment in order to be included in the initial set of segments.} \item{...}{Not used.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the estimated LOH threshold as a \code{\link[base]{numeric}} scalar or -\code{\link[base:is.finite]{Inf}}. In case it is not possible to estimate the LOH threshold, then -\code{\link[base:is.finite]{Inf}} is returned. } \details{ This method requires that calls for allelic balances already have been me made, cf. \code{\link[PSCBS:callAllelicBalance.PairedPSCBS]{*callAllelicBalance}()}. } \section{Algorithm}{ \itemize{ \item Grabs the segment-level C1 estimates. \item Calculate segment weights proportional to the number of heterozygous SNPs. \item Estimate the C1=1 location as the weighted median C1 for segments that have been called to be in allelic balance. \item Estimate the C1=0 location as the smallest C1 among segments that are not in allelic balance. \item Let the LOH threshold be the midpoint of the estimates C1=0 and C1=1 locations. } } \author{Henrik Bengtsson} \seealso{ Instead of calling this method explicitly, it is recommended to use the \code{\link[PSCBS:estimateDeltaLOH.PairedPSCBS]{*estimateDeltaLOH}()} method. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/mergeTwoSegments.PairedPSCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000002366�15000477031�017467� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{mergeTwoSegments.PairedPSCBS} \alias{mergeTwoSegments.PairedPSCBS} \alias{PairedPSCBS.mergeTwoSegments} \alias{mergeTwoSegments,PairedPSCBS-method} \title{Merge two neighboring segments} \description{ Merge two neighboring segments by recalculating segment statistics. } \usage{ \method{mergeTwoSegments}{PairedPSCBS}(this, left, update=TRUE, verbose=FALSE, ...) } \arguments{ \item{left}{An \code{\link[base]{integer}} specifying the segments (left, left+1) to be merged.} \item{update}{If \code{\link[base:logical]{TRUE}}, segment statistics are updated.} \item{verbose}{A \code{\link[base]{logical}} or a \code{\link[R.utils]{Verbose}} object.} \item{...}{Not used.} } \value{ Returns a \code{\link{PairedPSCBS}} with one less segment. } \author{Henrik Bengtsson} \seealso{ To drop regions (a connected set of segments) see \code{dropRegions()}. For more information see \code{\link{PairedPSCBS}}. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/plotTracks.AbstractCBS.Rd�����������������������������������������������������������������0000644�0001762�0000144�00000001431�15000477031�016402� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.PLOT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{plotTracks.AbstractCBS} \alias{plotTracks.AbstractCBS} \alias{AbstractCBS.plotTracks} \alias{plotTracks,AbstractCBS-method} \title{Plots the segmentation result along the genome} \description{ Plots the segmentation result along the genome. } \usage{ \method{plotTracks}{AbstractCBS}(...) } \arguments{ \item{...}{...} } \value{ Returns nothing. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/PSCBS-package.Rd��������������������������������������������������������������������������0000644�0001762�0000144�00000005170�15000477031�014431� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % 999.package.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{PSCBS-package} \alias{PSCBS-package} \docType{package} \title{Package PSCBS} \description{ Segmentation of allele-specific DNA copy number data and detection of regions with abnormal copy number within each parental chromosome. Both tumor-normal paired and tumor-only analyses are supported.. This package should be considered to be in an alpha or beta phase. You should expect the API to be changing over time. } \section{Installation and updates}{ To install this package, use \code{install.packages("PSCBS")}. } \section{To get started}{ To get started, see: \enumerate{ \item Vignettes '\href{../doc/index.html}{Parent-specific copy-number segmentation using Paired PSCBS}' and '\href{../doc/index.html}{Total copy-number segmentation using CBS}'. \item \code{\link{segmentByCBS}}() - segments total copy-numbers, or any other unimodal genomic signals, using the CBS method [3,4]. \item \code{\link{segmentByPairedPSCBS}}() - segments allele-specific tumor signal from a tumor \emph{with} a matched normal using the Paired PSCBS method [1,2]. \item \code{\link{segmentByNonPairedPSCBS}}() - segments allele-specific tumor signal from a tumor \emph{without} a matched normal using the Non-Paired PSCBS method adopted from [1,2]. } } \section{How to cite}{ Please use [1] and [2] to cite when using Paired PSCBS, and [3] and [4] when using CBS. When using Non-Paired PSCBS, please cite [1] and [2] as well. } \author{Henrik Bengtsson} \section{License}{ GPL (>= 2). } \references{ [1] A.B. Olshen, H. Bengtsson, P. Neuvial, P.T. Spellman, R.A. Olshen, V.E. Seshan, \emph{Parent-specific copy number in paired tumor-normal studies using circular binary segmentation}, Bioinformatics, 2011 \cr [2] H. Bengtsson, P. Neuvial and T.P. Speed, \emph{TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays}, BMC Bioinformatics, 2010 \cr [3] A.B. Olshen, E.S. Venkatraman (aka Venkatraman E. Seshan), R. Lucito and M. Wigler, \emph{Circular binary segmentation for the analysis of array-based DNA copy number data}, Biostatistics, 2004 \cr [4] E.S. Venkatraman and A.B. Olshen, \emph{A faster circular binary segmentation algorithm for the analysis of array CGH data}, Bioinformatics, 2007 \cr } \keyword{package} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getFractionOfGenomeLost.CBS.Rd������������������������������������������������������������0000644�0001762�0000144�00000003204�15000477031�017317� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getFractionOfGenomeLost.CBS} \alias{getFractionOfGenomeLost.CBS} \alias{CBS.getFractionOfGenomeLost} \alias{getFractionOfGenomeLost,CBS-method} \alias{CBS.getFractionOfGenomeGained} \alias{getFractionOfGenomeGained.CBS} \alias{getFractionOfGenomeGained,CBS-method} \alias{CBS.getFractionOfGenomeAltered} \alias{getFractionOfGenomeAltered.CBS} \alias{getFractionOfGenomeAltered,CBS-method} \alias{CBS.getFGL} \alias{getFGL.CBS} \alias{getFGL,CBS-method} \alias{CBS.getFGG} \alias{getFGG.CBS} \alias{getFGG,CBS-method} \alias{CBS.getFGA} \alias{getFGA.CBS} \alias{getFGA,CBS-method} \title{Calculates the fraction of the genome lost, gained, or aberrant either way} \description{ Calculates the fraction of the genome lost, gained, or aberrant either way (in sense of total copy numbers), using definitions closely related to those presented in [1]. } \usage{ \method{getFractionOfGenomeLost}{CBS}(fit, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns a \code{\link[base]{double}} in [0,1]. } \author{Henrik Bengtsson} \references{ [1] Fridlyand et al. \emph{Breast tumor copy number aberration phenotypes and genomic instability}, BMC Cancer, 2006. \cr } \seealso{ Internally, \code{\link[PSCBS:getCallStatistics.CBS]{*getCallStatistics}()} is used. For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/bootstrapTCNandDHByRegion.PairedPSCBS.Rd��������������������������������������������������0000644�0001762�0000144�00000003773�15000477031�021113� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.BOOT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{bootstrapTCNandDHByRegion.PairedPSCBS} \alias{bootstrapTCNandDHByRegion.PairedPSCBS} \alias{PairedPSCBS.bootstrapTCNandDHByRegion} \alias{bootstrapTCNandDHByRegion,PairedPSCBS-method} \title{Estimate confidence intervals of TCN and DH segment levels} \description{ Estimate confidence intervals of TCN and DH segment levels using bootstrap. } \usage{ \method{bootstrapTCNandDHByRegion}{PairedPSCBS}(fit, B=1000L, boot=NULL, ..., probs=c(0.025, 0.05, 0.95, 0.975), statsFcn=NULL, what=c("segment", "changepoint"), force=FALSE, verbose=FALSE, .debug=FALSE) } \arguments{ \item{B}{A positive \code{\link[base]{integer}} specifying the number of bootstrap samples.} \item{boot}{Alternatively, to generating \code{B} bootstrap samples, this specifies a pre-generated set of bootstrap samples as returned by \code{bootstrapSegmentsAndChangepoints()}.} \item{...}{Additional arguments passed to \code{bootstrapSegmentsAndChangepoints()}.} \item{probs}{The default quantiles to be estimated.} \item{statsFcn}{A (optional) \code{\link[base]{function}} that estimates confidence intervals given locus-level data. If \code{\link[base]{NULL}}, the \code{\link[stats]{quantile}} function is used.} \item{what}{A \code{\link[base]{character}} \code{\link[base]{vector}} specifying what to bootstrap.} \item{force}{If \code{\link[base:logical]{TRUE}}, already existing estimates are ignored, otherwise not.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} \item{.debug}{(internal) If \code{\link[base:logical]{TRUE}}, additional sanity checks are performed internally.} } \value{ Returns a \code{\link{PairedPSCBS}} object. } \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} �����PSCBS/man/segmentByCBS.Rd���������������������������������������������������������������������������0000644�0001762�0000144�00000021767�15000477031�014465� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % segmentByCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{segmentByCBS} \alias{segmentByCBS.default} \alias{segmentByCBS} \alias{segmentByCBS.data.frame} \alias{segmentByCBS.CBS} \alias{segmentByCBS.CNA} \alias{segmentByCBS} \title{Segment genomic signals using the CBS method} \description{ Segment genomic signals using the CBS method of the \pkg{DNAcopy} package. This is a convenient low-level wrapper for the \code{DNAcopy::segment()} method. It is intended to be applied to a sample at the time. For more details on the Circular Binary Segmentation (CBS) method see [1,2]. } \usage{ \method{segmentByCBS}{default}(y, chromosome=0L, x=NULL, index=seq_along(y), w=NULL, undo=0, avg=c("mean", "median"), ..., joinSegments=TRUE, knownSegments=NULL, seed=NULL, verbose=FALSE) } \arguments{ \item{y}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genomic signals to be segmented.} \item{chromosome}{Optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of length J, specifying the chromosome of each loci. If a scalar, it is expanded to a vector of length J.} \item{x}{Optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genomic locations. If \code{\link[base]{NULL}}, index locations \code{1:J} are used.} \item{index}{An optional \code{\link[base]{integer}} \code{\link[base]{vector}} of length J specifying the genomewide indices of the loci.} \item{w}{Optional \code{\link[base]{numeric}} \code{\link[base]{vector}} in [0,1] of J weights.} \item{undo}{A non-negative \code{\link[base]{numeric}}. If greater than zero, then arguments \code{undo.splits="sdundo"} and \code{undo.SD=undo} are passed to \code{DNAcopy::segment()}. In the special case when \code{undo} is +\code{\link[base:is.finite]{Inf}}, the segmentation result will not contain any changepoints (in addition to what is specified by argument \code{knownSegments}).} \item{avg}{A \code{\link[base]{character}} string specifying how to calculating segment mean levels \emph{after} change points have been identified.} \item{...}{Additional arguments passed to the \code{DNAcopy::segment()} segmentation function.} \item{joinSegments}{If \code{\link[base:logical]{TRUE}}, there are no gaps between neighboring segments. If \code{\link[base:logical]{FALSE}}, the boundaries of a segment are defined by the support that the loci in the segments provides, i.e. there exist a locus at each end point of each segment. This also means that there is a gap between any neighboring segments, unless the change point is in the middle of multiple loci with the same position. The latter is what \code{DNAcopy::segment()} returns. } \item{knownSegments}{Optional \code{\link[base]{data.frame}} specifying \emph{non-overlapping} known segments. These segments must not share loci. See \code{\link{findLargeGaps}}() and \code{\link{gapsToSegments}}().} \item{seed}{An (optional) \code{\link[base]{integer}} specifying the random seed to be set before calling the segmentation method. The random seed is set to its original state when exiting. If \code{\link[base]{NULL}}, it is not set.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link{CBS}} object. } \details{ Internally \code{\link[DNAcopy]{segment}} of \pkg{DNAcopy} is used to segment the signals. This segmentation method support weighted segmentation. } \section{Reproducibility}{ The \code{DNAcopy::segment()} implementation of CBS uses approximation through random sampling for some estimates. Because of this, repeated calls using the same signals may result in slightly different results, unless the random seed is set/fixed. } \section{Missing and non-finite values}{ Signals may contain missing values (\code{\link[base]{NA}} or \code{\link[base:is.finite]{NaN}}), but not infinite values (+/-\code{\link[base:is.finite]{Inf}}). Loci with missing-value signals are preserved and keep in the result. Likewise, genomic positions may contain missing values. However, if they do, such loci are silently excluded before performing the segmentation, and are not kept in the results. The mapping between the input locus-level data and ditto of the result can be inferred from the \code{index} column of the locus-level data of the result. None of the input data may have infinite values, i.e. -\code{\link[base:is.finite]{Inf}} or +\code{\link[base:is.finite]{Inf}}. If so, an informative error is thrown. } \examples{ # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x) print(fit) plotTracks(fit) xlab <- "Position (Mb)" ylim <- c(-3,3) xMb <- x/1e6 plot(xMb,y, pch=20, col="#aaaaaa", xlab=xlab, ylim=ylim) drawLevels(fit, col="red", lwd=2, xScale=1e-6) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # TESTS # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x, seed=0xBEEF) print(fit) ## id chromosome start end nbrOfLoci mean ## 1 y 0 55167.82 20774251 201 0.0164 ## 2 y 0 20774250.85 29320105 99 1.0474 ## 3 y 0 29320104.86 65874675 349 -0.0227 ## 4 y 0 65874675.06 81348129 151 -1.0813 ## 5 y 0 81348129.20 99910827 200 -0.0612 # Test #1: Reverse the ordering and segment fitR <- segmentByCBS(rev(y), x=rev(x), seed=0xBEEF) # Sanity check stopifnot(all.equal(getSegments(fitR), getSegments(fit))) # Sanity check stopifnot(all.equal(rev(getLocusData(fitR)$index), getLocusData(fit)$index)) # Test #2: Reverse, but preserve ordering of 'data' object fitRP <- segmentByCBS(rev(y), x=rev(x), preserveOrder=TRUE) stopifnot(all.equal(getSegments(fitRP), getSegments(fit))) # (Test #3: Change points inbetween data points at the same locus) x[650:654] <- x[649] fitC <- segmentByCBS(rev(y), x=rev(x), preserveOrder=TRUE, seed=0xBEEF) # Test #4: Allow for some missing values in signals y[450] <- NA fitD <- segmentByCBS(y, x=x, seed=0xBEEF) # Test #5: Allow for some missing genomic annotations x[495] <- NA fitE <- segmentByCBS(y, x=x, seed=0xBEEF) # Test #6: Undo all change points found fitF <- segmentByCBS(y, x=x, undo=Inf, seed=0xBEEF) print(fitF) stopifnot(nbrOfSegments(fitF) == 1L) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # MISC. # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Emulate a centromere x[650:699] <- NA fit <- segmentByCBS(y, x=x, seed=0xBEEF) xMb <- x/1e6 plot(xMb,y, pch=20, col="#aaaaaa", xlab=xlab, ylim=ylim) drawLevels(fit, col="red", lwd=2, xScale=1e-6) fitC <- segmentByCBS(y, x=x, joinSegments=FALSE, seed=0xBEEF) drawLevels(fitC, col="blue", lwd=2, xScale=1e-6) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Multiple chromosomes # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Appending CBS results fit1 <- segmentByCBS(y, chromosome=1, x=x) fit2 <- segmentByCBS(y, chromosome=2, x=x) fit <- c(fit1, fit2) print(fit) plotTracks(fit, subset=NULL, lwd=2, Clim=c(-3,3)) # Segmenting multiple chromosomes at once chromosomeWG <- rep(1:2, each=J) xWG <- rep(x, times=2) yWG <- rep(y, times=2) fitWG <- segmentByCBS(yWG, chromosome=chromosomeWG, x=xWG) print(fitWG) plotTracks(fitWG, subset=NULL, lwd=2, Clim=c(-3,3)) # Assert same results fit$data[,"index"] <- getLocusData(fitWG)[,"index"] # Ignore 'index' stopifnot(all.equal(getLocusData(fitWG), getLocusData(fit))) stopifnot(all.equal(getSegments(fitWG), getSegments(fit))) } \author{Henrik Bengtsson} \references{ [1] A.B. Olshen, E.S. Venkatraman (aka Venkatraman E. Seshan), R. Lucito and M. Wigler, \emph{Circular binary segmentation for the analysis of array-based DNA copy number data}, Biostatistics, 2004 \cr [2] E.S. Venkatraman and A.B. Olshen, \emph{A faster circular binary segmentation algorithm for the analysis of array CGH data}, Bioinformatics, 2007 \cr } \seealso{ To segment allele-specific tumor copy-number signals from a tumor \emph{with} a matched normal, see \code{\link{segmentByPairedPSCBS}}(). For the same \emph{without} a matched normal, see \code{\link{segmentByNonPairedPSCBS}}(). It is also possible to prune change points after segmentation (with identical results) using \code{\link[PSCBS:pruneBySdUndo.CBS]{pruneBySdUndo}()}. } \keyword{IO} ���������PSCBS/man/callROH.PairedPSCBS.Rd��������������������������������������������������������������������0000644�0001762�0000144�00000003072�15000477031�015447� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callROH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callROH.PairedPSCBS} \alias{callROH.PairedPSCBS} \alias{PairedPSCBS.callROH} \alias{callROH,PairedPSCBS-method} \alias{callROH.NonPairedPSCBS} \title{Calls segments that are in ROH} \description{ Calls segments that are in ROH, i.e. that have no (true) heterozygous genotypes. Run of homozygosity (ROH) is a property of the normal (germline) sample. } \usage{ \method{callROH}{PairedPSCBS}(fit, ..., updateMeans=TRUE, force=FALSE, verbose=FALSE) } \arguments{ \item{...}{Additional arguments passed to \code{\link{testROH}}().} \item{updateMeans}{If \code{\link[base:logical]{TRUE}}, DH and (C1,C2) mean levels are set to \code{\link[base]{NA}} for segments called ROH, otherwise not.} \item{force}{If \code{\link[base:logical]{FALSE}}, and ROH calls already exits, then nothing is done, otherwise the calls are done.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link{PairedPSCBS}} object with ROH calls. } \author{Pierre Neuvial, Henrik Bengtsson} \seealso{ Internally, \code{\link{testROH}}() is used. To call allelic balance (AB) see \code{\link[PSCBS:callAB.PairedPSCBS]{*callAB}()}. To call loss of heterozygosity (LOH) see \code{\link[PSCBS:callLOH.PairedPSCBS]{*callLOH}()}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/Restructuring_AbstractCBS_objects.Rd������������������������������������������������������0000644�0001762�0000144�00000005305�15000477031�020732� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{Restructuring AbstractCBS objects} \alias{Restructuring AbstractCBS objects} \title{Restructuring AbstractCBS objects} \alias{RestructPSCBS} \description{ This page describes available methods for restructuring an \code{\link{AbstractCBS}} object. \itemize{ \item \code{\link[PSCBS:extractChromosomes.AbstractCBS]{*extractChromosomes}()} / \code{\link[PSCBS:extractChromosome.AbstractCBS]{*extractChromosome}()} - Extracts an \code{\link{AbstractCBS}} with the specified chromosomes. \item \code{\link[PSCBS:extractSegments.AbstractCBS]{*extractSegments}()} / \code{\link[PSCBS:extractSegment.AbstractCBS]{*extractSegment}()} - Extracts an \code{\link{AbstractCBS}} with the specified segments. \item \code{\link[PSCBS:extractRegions.AbstractCBS]{*extractRegions}()} / \code{\link[PSCBS:extractRegion.AbstractCBS]{*extractRegion}()} - Extracts an \code{\link{AbstractCBS}} with the specified regions each of a certain size, where a region is defined as a connected set of segments. \item \code{\link[PSCBS:dropRegions.AbstractCBS]{*dropRegions}()} / \code{\link[PSCBS:dropRegion.AbstractCBS]{*dropRegion}()} - Drops specified regions and returns an \code{\link{AbstractCBS}} without them. \item \code{\link[PSCBS:dropChangePoint.AbstractCBS]{*dropChangePoint}()} / \code{\link[PSCBS:mergeTwoSegments.AbstractCBS]{*mergeTwoSegments}()} - Drops a change point by merging two neighboring segments and recalculates the statistics for the merged segment before returning an \code{\link{AbstractCBS}}. \item \code{\link[PSCBS:dropChangePoints.AbstractCBS]{*dropChangePoints}()} - Drops zero or more change points and recalculates the segment statistics before returning an \code{\link{AbstractCBS}}. \item \code{\link[PSCBS:mergeThreeSegments.AbstractCBS]{*mergeThreeSegments}()} - Merges a segment with its two flanking segments and recalculates the statistics for the merged segment before returning an \code{\link{AbstractCBS}}. } All of the above methods are implemented for \code{\link{CBS}} and \code{\link{PairedPSCBS}} objects. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{documentation} \keyword{internal} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callSegmentationOutliers.Rd���������������������������������������������������������������0000644�0001762�0000144�00000004712�15000477031�017207� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % callSegmentationOutliers.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callSegmentationOutliers} \alias{callSegmentationOutliers} \alias{callSegmentationOutliers.default} \alias{callSegmentationOutliers.data.frame} \alias{dropSegmentationOutliers} \alias{dropSegmentationOutliers.default} \alias{dropSegmentationOutliers.data.frame} \title{Calls/drops single-locus outliers along the genome} \description{ Calls/drops single-locus outliers along the genome that have a signal that differ significantly from the neighboring loci. } \usage{ \method{callSegmentationOutliers}{default}(y, chromosome=0, x=NULL, method="DNAcopy::smooth.CNA", ..., verbose=FALSE) \method{callSegmentationOutliers}{data.frame}(y, ...) \method{dropSegmentationOutliers}{default}(y, ...) \method{dropSegmentationOutliers}{data.frame}(y, ...) } \arguments{ \item{y}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genomic signals to be segmented.} \item{chromosome}{(Optional) An \code{\link[base]{integer}} scalar (or a \code{\link[base]{vector}} of length J contain a unique value). Only used for annotation purposes.} \item{x}{Optional \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genomic locations. If \code{\link[base]{NULL}}, index locations \code{1:J} are used.} \item{method}{A \code{\link[base]{character}} string specifying the method used for calling outliers.} \item{...}{Additional arguments passed to internal outlier detection method.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ \code{callSegmentationOutliers()} returns a \code{\link[base]{logical}} \code{\link[base]{vector}} of length J. \code{dropSegmentationOutliers()} returns an object of the same type as argument \code{y}, where the signals for which outliers were called have been set to \code{\link[base]{NA}}. } \section{Missing and non-finite values}{ Signals as well as genomic positions may contain missing values, i.e. \code{\link[base]{NA}}s or \code{\link[base:is.finite]{NaN}}s. By definition, these cannot be outliers. } \author{Henrik Bengtsson} \seealso{ Internally \code{\link[DNAcopy]{smooth.CNA}} is utilized to identify the outliers. } \keyword{methods} \keyword{IO} ������������������������������������������������������PSCBS/man/plotTracks.CBS.Rd�������������������������������������������������������������������������0000644�0001762�0000144�00000002355�15000477031�014724� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.PLOT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{plotTracks.CBS} \alias{plotTracks.CBS} \alias{CBS.plotTracks} \alias{plotTracks,CBS-method} \title{Plots copy numbers along the genome} \description{ Plots copy numbers along the genome for one or more chromosomes. Each type of track is plotted in its own panel. } \usage{ \method{plotTracks}{CBS}(x, scatter=TRUE, pch=20, col="gray", meanCol="purple", cex=1, grid=FALSE, Clim="auto", xScale=1e-06, Clab="auto", ..., byIndex=FALSE, mar=NULL, add=FALSE) } \arguments{ \item{x}{A result object returned by \code{\link{segmentByCBS}}().} \item{pch}{The type of points to use.} \item{Clim}{The range of copy numbers.} \item{xScale}{The scale factor used for genomic positions.} \item{...}{Not used.} \item{add}{If \code{\link[base:logical]{TRUE}}, the panels plotted are added to the existing plot, otherwise a new plot is created.} } \value{ Returns nothing. } \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} \keyword{IO} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/mergeTwoSegments.AbstractCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000002472�15000477031�017561� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{mergeTwoSegments.AbstractCBS} \alias{mergeTwoSegments.AbstractCBS} \alias{AbstractCBS.mergeTwoSegments} \alias{mergeTwoSegments,AbstractCBS-method} \alias{AbstractCBS.dropChangePoint} \alias{dropChangePoint.AbstractCBS} \alias{dropChangePoint,AbstractCBS-method} \title{Merge two neighboring segments} \description{ Merge two neighboring segments into one segment, which is done by dropping their common change point and recalculating the segment statistics. } \usage{ \method{mergeTwoSegments}{AbstractCBS}(...) } \arguments{ \item{...}{Not used.} } \value{ Returns an \code{\link{AbstractCBS}} of the same class with one less segment. } \author{Henrik Bengtsson} \seealso{ To merge a segment and its two flanking segments, see \code{\link[PSCBS:mergeThreeSegments.AbstractCBS]{*mergeThreeSegments}()}. To drop regions (a connected set of segments) see \code{\link[PSCBS:dropRegions.AbstractCBS]{*dropRegions}()}. For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/as.data.frame.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000001627�15000477031�016667� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{as.data.frame.AbstractCBS} \alias{as.data.frame.AbstractCBS} \alias{AbstractCBS.as.data.frame} \alias{as.data.frame,AbstractCBS-method} \title{Gets the table of segments} \description{ Gets the table of segments. } \usage{ \method{as.data.frame}{AbstractCBS}(x, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns a \code{\link[base]{data.frame}}, where each row corresponds to a unique segment. } \author{Henrik Bengtsson} \seealso{ Utilizes \code{\link[PSCBS:getSegments.AbstractCBS]{*getSegments}()}. For more information see \code{\link{AbstractCBS}}.. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������PSCBS/man/writeSegments.PSCBS.Rd��������������������������������������������������������������������0000644�0001762�0000144�00000003067�15000477031�015702� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PSCBS.IO.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{writeSegments.PSCBS} \alias{writeSegments.PSCBS} \alias{PSCBS.writeSegments} \alias{writeSegments,PSCBS-method} \title{Writes the table of segments to file} \description{ Writes the table of segments to file. } \usage{ \method{writeSegments}{PSCBS}(fit, name=getSampleName(fit), tags=NULL, ext="tsv", path=NULL, addHeader=TRUE, createdBy=NULL, sep="\t", nbrOfDecimals=4L, splitters=FALSE, overwrite=FALSE, skip=FALSE, ...) } \arguments{ \item{name, tags}{Name and optional tags part of the filename}. \item{path}{The directory where the file will be written.} \item{addHeader}{If \code{\link[base:logical]{TRUE}}, header comments are written.} \item{createdBy}{A header comment of whom created the file.} \item{splitters}{If \code{\link[base:logical]{TRUE}}, each chromosome is separated by a row of missing values.} \item{overwrite, skip}{If an output file already exists, these arguments specifies what should happen.} \item{...}{Additional arguments pass to \code{getSegments()}.} } \value{ Returns the pathname of the the file written. } \author{Henrik Bengtsson} \seealso{ Utilizes \code{\link[PSCBS:getSegments.PSCBS]{*getSegments}()}. For more information see \code{\link{PSCBS}}.. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/setSampleName.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000001734�15000477031�017020� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{setSampleName.AbstractCBS} \alias{setSampleName.AbstractCBS} \alias{AbstractCBS.setSampleName} \alias{setSampleName,AbstractCBS-method} \alias{AbstractCBS.sampleName<-} \alias{sampleName<-.AbstractCBS} \alias{sampleName<-,AbstractCBS-method} \title{Sets the name of the sample segmented} \description{ Sets the name of the sample segmented. } \usage{ \method{setSampleName}{AbstractCBS}(fit, name, ...) } \arguments{ \item{name}{A \code{\link[base]{character}} string.} \item{...}{Not used.} } \value{ Returns (invisibly) an updated object. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}.. } \keyword{internal} \keyword{methods} ������������������������������������PSCBS/man/callLOH.PairedPSCBS.Rd��������������������������������������������������������������������0000644�0001762�0000144�00000005077�15000477031�015450� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callLOH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callLOH.PairedPSCBS} \alias{callLOH.PairedPSCBS} \alias{PairedPSCBS.callLOH} \alias{callLOH,PairedPSCBS-method} \title{Calls segments that are in LOH} \description{ Calls segments that are in LOH, i.e. that have "zero" minor copy number. } \usage{ \method{callLOH}{PairedPSCBS}(fit, flavor=c("SmallC1", "LargeDH"), ..., minSize=1, xorCalls=TRUE, force=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of call to use.} \item{...}{Additional arguments passed to the caller.} \item{minSize}{An optional \code{\link[base]{integer}} specifying the minimum number of data points in order to call a segments. If fewer data points, then the call is set to \code{\link[base]{NA}} regardless.} \item{xorCalls}{If \code{\link[base:logical]{TRUE}}, a region already called AB, will for consistency never be called LOH, resulting in either an LOH call set to \code{\link[base:logical]{FALSE}} or \code{\link[base]{NA}} (as explained below).} \item{force}{If \code{\link[base:logical]{FALSE}}, and allelic-balance calls already exits, then nothing is done, otherwise the calls are done.} } \value{ Returns a \code{\link{PairedPSCBS}} object with LOH calls. } \section{AB and LOH consistency}{ Biologically, a segment can not be both in allelic balance (AB) and in loss-of-heterozygosity (LOH) at the same time. To avoid reporting such inconsistencies, the LOH caller will, if argument \code{xorCalls=TRUE}, never report a segment to be in LOH if it is already called to be in AB. However, regardless of of the AB call, a segment is still always tested for LOH, to check weather the LOH caller is consistent with the AB caller or not. Thus, in order to distinguish the case where the AB caller and LOH caller agree from when they disagree, we report either (AB,LOH)=(TRUE,FALSE) or (TRUE,NA). The former is reported when they are consistent, and the latter when they are not, or when the LOH caller could not call it. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:callLowC1ByC1.PairedPSCBS]{*callLowC1ByC1}()}, \code{\link[PSCBS:callExtremeAllelicImbalanceByDH.PairedPSCBS]{*callExtremeAllelicImbalanceByDH}()}. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getCallStatistics.CBS.Rd������������������������������������������������������������������0000644�0001762�0000144�00000004441�15000477031�016222� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getCallStatistics.CBS} \alias{getCallStatistics.CBS} \alias{CBS.getCallStatistics} \alias{getCallStatistics,CBS-method} \title{Calculates various call statistics per chromosome} \description{ Calculates various call statistics per chromosome. } \usage{ \method{getCallStatistics}{CBS}(fit, regions=NULL, shrinkRegions=TRUE, ..., verbose=FALSE) } \arguments{ \item{regions}{An optional \code{\link[base]{data.frame}} with columns "chromosome", "start", and "end" specifying the regions of interest to calculate statistics for. If \code{\link[base]{NULL}}, all of the genome is used.} \item{shrinkRegions}{If \code{\link[base:logical]{TRUE}}, regions are shrunk to the support of the data.} \item{...}{Not used.} \item{verbose}{\code{\link[R.utils]{Verbose}}.} } \value{ Returns a CxK \code{\link[base]{data.frame}}, where C is the number of regions that meet the criteria setup by argument \code{regions} and (K-4)/2 is the number of call types. The first column is the chromosome index, the second and the third are the first and last position, and the fourth the length (=last-first+1) of the chromosome. The following columns contains call summaries per chromosome. For each chromosome and call type, the total length of such calls on that chromosome is reported together how large of a fraction of the chromosome such calls occupy. } \details{ The estimators implemented here are based solely on the segmentation results, which is very fast. In the original proposal by Fridlyand et al. [1], the authors estimates the parameters by converting segment-level calls back to locus-level calls and there do the calculations. The difference between the two approaches should be minor, particularly for large density arrays. } \author{Henrik Bengtsson} \references{ [1] Fridlyand et al. \emph{Breast tumor copy number aberration phenotypes and genomic instability}, BMC Cancer, 2006. \cr } \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/mergeThreeSegments.AbstractCBS.Rd���������������������������������������������������������0000644�0001762�0000144�00000002400�15000477031�020046� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{mergeThreeSegments.AbstractCBS} \alias{mergeThreeSegments.AbstractCBS} \alias{AbstractCBS.mergeThreeSegments} \alias{mergeThreeSegments,AbstractCBS-method} \title{Merge a segment and its two flanking segments} \description{ Merge a segment and its two flanking segments into one segment, and recalculating the segment statistics. } \usage{ \method{mergeThreeSegments}{AbstractCBS}(fit, middle, ...) } \arguments{ \item{middle}{An \code{\link[base]{integer}} specifying the three segments (middle-1, middle, middle+1) to be merged.} \item{...}{Additional arguments passed to \code{\link[PSCBS:mergeTwoSegments.AbstractCBS]{*mergeTwoSegments}()}.} } \value{ Returns an \code{\link{AbstractCBS}} of the same class with two less segment. } \author{Henrik Bengtsson} \seealso{ Internally \code{\link[PSCBS:mergeTwoSegments.AbstractCBS]{*mergeTwoSegments}()} is used. For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/pruneByHClust.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000003031�15000477031�017021� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.HCLUST.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{pruneByHClust.AbstractCBS} \alias{pruneByHClust.AbstractCBS} \alias{AbstractCBS.pruneByHClust} \alias{pruneByHClust,AbstractCBS-method} \title{Prunes the CN profile by pruning and merging through hierarchical clustering} \description{ Prunes the CN profile by pruning and merging through hierarchical clustering. } \usage{ \method{pruneByHClust}{AbstractCBS}(fit, ..., size=NULL, distMethod="euclidean", hclustMethod="ward.D", merge=TRUE, update=TRUE, verbose=FALSE) } \arguments{ \item{...}{Arguments passed to \code{\link[stats]{cutree}}, particularly either of thresholds \code{h} or \code{k}.} \item{size, distMethod, hclustMethod}{Arguments (as well as some of \code{...}) passed to \code{\link[PSCBS:hclustCNs.AbstractCBS]{*hclustCNs}()}.} \item{merge}{If \code{\link[base:logical]{TRUE}}, consecutive segments that belong to the same PSCN cluster will be merged into one large segment.} \item{update}{If \code{\link[base:logical]{TRUE}}, segment means are updated afterwards, otherwise not.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a pruned object of the same class. } \examples{\dontrun{ fitP <- pruneByHClust(fit, h=0.25) }} \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/as.DNAcopy.CBS.Rd�������������������������������������������������������������������������0000644�0001762�0000144�00000003422�15000477031�014471� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % DNAcopy.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{as.DNAcopy.CBS} \alias{as.DNAcopy.CBS} \alias{CBS.as.DNAcopy} \alias{as.DNAcopy,CBS-method} \title{Coerces a CBS object to a DNAcopy object} \description{ Coerces a CBS object to a DNAcopy object. } \usage{ \method{as.DNAcopy}{CBS}(fit, ...) } \arguments{ \item{fit}{A \code{\link{CBS}} object."} \item{...}{Not used.} } \value{ Returns a \code{\link[DNAcopy:DNAcopy]{DNAcopy}} object (of the \pkg{DNAcopy} package). } \examples{ # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x) print(fit) plotTracks(fit) # Coerce an CBS object to a DNAcopy object fitD <- as.DNAcopy(fit) # Coerce an DNAcopy object to a CBS object fitC <- as.CBS(fitD) # Sanity check fitD2 <- as.DNAcopy(fit) stopifnot(all.equal(fitD2, fitD)) fitC2 <- as.CBS(fitD2) stopifnot(all.equal(fitC2, fitC)) } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:as.CBS.DNAcopy]{as.CBS()}}. For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/report.AbstractCBS.Rd���������������������������������������������������������������������0000644�0001762�0000144�00000003143�15000477031�015571� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.REPORT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{report.AbstractCBS} \alias{report.AbstractCBS} \alias{AbstractCBS.report} \alias{report,AbstractCBS-method} \title{Generates a report of the segmentation results} \description{ Generates a report of the segmentation results. Currently reports can be generated for segmentation results of class \code{\link{CBS}} and \code{\link{PairedPSCBS}}. } \usage{ \method{report}{AbstractCBS}(fit, sampleName=getSampleName(fit), studyName, ..., rspTags=NULL, rootPath="reports/", .filename="*", skip=TRUE, envir=new.env(), verbose=FALSE) } \arguments{ \item{fit}{An \code{\link{AbstractCBS}} object.} \item{sampleName}{A \code{\link[base]{character}} string specifying the name of the sample segmented.} \item{studyName}{A \code{\link[base]{character}} string specifying the name of study/project.} \item{...}{Optional arguments passed to the RSP template.} \item{rspTags}{Optional \code{\link[base]{character}} \code{\link[base]{vector}} of tags for further specifying which RSP report to generate.} \item{rootPath}{The root directory where to write the report.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the pathname of the generated PDF. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/figures/����������������������������������������������������������������������������������0000755�0001762�0000144�00000000000�14564051545�013354� 5����������������������������������������������������������������������������������������������������ustar 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For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ��������PSCBS/man/estimateDeltaABBySmallDH.PairedPSCBS.Rd���������������������������������������������������0000644�0001762�0000144�00000004300�15000477031�020646� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateDeltaAB.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateDeltaABBySmallDH.PairedPSCBS} \alias{estimateDeltaABBySmallDH.PairedPSCBS} \alias{PairedPSCBS.estimateDeltaABBySmallDH} \alias{estimateDeltaABBySmallDH,PairedPSCBS-method} \title{Estimate a threshold for calling allelic balance from DH} \description{ Estimate a threshold for calling allelic balance from DH. } \usage{ \method{estimateDeltaABBySmallDH}{PairedPSCBS}(fit, q1=0.05, q2=0.9, ..., verbose=FALSE) } \arguments{ \item{q1}{A \code{\link[base]{numeric}} value specifying the weighted quantile of the segment-level DHs used to identify segments with small DH means.} \item{q2}{A \code{\link[base]{numeric}} value specifying the quantile of the locus-level DH signals for those segments with small DH mean levels.} \item{...}{Not used.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the threshold estimate as a \code{\link[base]{numeric}} scalar. } \section{Algorithm}{ \itemize{ \item Grabs the segment-level DH estimates. \item Calculate segment weights proportional to the number of heterozygous SNPs. \item Calculate \eqn{\Delta} as the 5\% quantile of the weighted DH means. \item Choose the segments with means less than \eqn{\Delta}. \item Calculate threshold \eqn{\Delta_{AB}} as the 90\% "symmetric" quantile of the observed locus-level DHs from the selected segments in Step 4. The q:th "symmetric" quantile is estimated by estimating the ((1-q), 50\%) quantiles, calculating their distance as "50\%-(1-q)" and add to the median (50\%), i.e. "median + (median-(1-q))" = "2*median-1 + q", which should equal q if the distribution is symmetric. } } \author{Henrik Bengtsson} \seealso{ Instead of calling this method explicitly, it is recommended to use the \code{\link[PSCBS:estimateDeltaAB.PairedPSCBS]{*estimateDeltaAB}()} method. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/pruneByDP.AbstractCBS.Rd������������������������������������������������������������������0000644�0001762�0000144�00000002502�15000477031�016124� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.PRUNE.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{pruneByDP.AbstractCBS} \alias{pruneByDP.AbstractCBS} \alias{AbstractCBS.pruneByDP} \alias{pruneByDP,AbstractCBS-method} \title{Prunes the CN profile using dynamical programming} \description{ Prunes the CN profile using dynamical programming by specifying the target number of segments or alternative how of many change points to drop. } \usage{ \method{pruneByDP}{AbstractCBS}(fit, nbrOfSegments, ..., verbose=FALSE) } \arguments{ \item{nbrOfSegments}{An \code{\link[base]{integer}} specifying the number of segments after pruning. If negative, the it specifies the number of change points to drop.} \item{...}{Optional arguments passed to \code{\link[PSCBS:seqOfSegmentsByDP.AbstractCBS]{*seqOfSegmentsByDP}()}.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a pruned object of the same class. } \examples{\dontrun{ # Drop two segments fitP <- pruneByDP(fit, nbrOfSegments=-2) }} \author{Henrik Bengtsson, Pierre Neuvial} \references{ [1] ... \cr } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/findLargeGaps.Rd��������������������������������������������������������������������������0000644�0001762�0000144�00000003233�15000477031�014672� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % findLargeGaps.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{findLargeGaps} \alias{findLargeGaps.default} \alias{findLargeGaps} \alias{findLargeGaps.data.frame} \title{Identifies gaps of a genome where there exist no observations} \description{ Identifies gaps of a genome where there exist no observations. } \usage{ \method{findLargeGaps}{default}(chromosome=NULL, x, minLength, resolution=1L, ...) } \arguments{ \item{chromosome}{(Optional) An \code{\link[base]{integer}} \code{\link[base]{vector}} of length J of chromosome indices.} \item{x}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J of genomic locations.} \item{minLength}{A positive \code{\link[base]{numeric}} scalar specifying the minimum length of a gap.} \item{resolution}{A non-negative \code{\link[base]{numeric}} specifying the minimum length unit, which by default equals one nucleotide/base pair.} \item{...}{Not used.} } \value{ Returns \code{\link[base]{data.frame}} zero or more rows and with columns \code{chromosome} (if given), \code{start}, \code{stop}, and \code{length}. } \author{Henrik Bengtsson} \seealso{ Use \code{\link{gapsToSegments}}() to turn the set of identified gaps into the complementary set of segments such that they can be passed to \code{\link{segmentByCBS}}(), \code{\link{segmentByPairedPSCBS}}() and \code{\link{segmentByNonPairedPSCBS}}() via argument \code{knownSegments}. } \keyword{IO} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/NonPairedPSCBS.Rd�������������������������������������������������������������������������0000644�0001762�0000144�00000005445�15000477031�014645� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % NonPairedPSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{NonPairedPSCBS} \docType{class} \alias{NonPairedPSCBS} \title{The NonPairedPSCBS class} \description{ Package: PSCBS \cr \bold{Class NonPairedPSCBS}\cr \code{list}\cr \code{~~|}\cr \code{~~+--}\code{\link[PSCBS]{AbstractCBS}}\cr \code{~~~~~~~|}\cr \code{~~~~~~~+--}\code{\link[PSCBS]{PSCBS}}\cr \code{~~~~~~~~~~~~|}\cr \code{~~~~~~~~~~~~+--}\emph{\code{NonPairedPSCBS}}\cr \bold{Directly known subclasses:}\cr \cr public abstract class \bold{NonPairedPSCBS}\cr extends \emph{\link[PSCBS]{PSCBS}}\cr A NonPairedPSCBS is an object containing the results from the Non-paired PSCBS method. } \usage{NonPairedPSCBS(fit=list(), ...)} \arguments{ \item{fit}{A \code{\link[base]{list}} structure containing the Non-paired PSCBS results.} \item{...}{Not used.} } \section{Fields and Methods}{ \bold{Methods:}\cr \emph{No methods defined}. \bold{Methods inherited from PSCBS}:\cr as.data.frame, c, drawChangePoints, extractChromosomes, extractWIG, getLocusData, getLocusSignalNames, getSegmentTrackPrefixes, isLocallyPhased, isSegmentSplitter, normalizeTotalCNs, writeSegments \bold{Methods inherited from AbstractCBS}:\cr adjustPloidyScale, all.equal, as.data.frame, clearCalls, drawChangePoints, drawKnownSegments, dropChangePoint, dropChangePoints, dropRegion, dropRegions, extractCNs, extractChromosome, extractChromosomes, extractRegions, extractSegments, extractWIG, getChangePoints, getChromosomeOffsets, getChromosomeRanges, getChromosomes, getLocusData, getLocusSignalNames, getMeanEstimators, getSampleName, getSegmentSizes, getSegmentTrackPrefixes, getSegments, mergeThreeSegments, mergeTwoSegments, nbrOfChangePoints, nbrOfChromosomes, nbrOfLoci, nbrOfSegments, normalizeTotalCNs, ploidy, ploidy<-, plotTracks, print, pruneByDP, pruneByHClust, renameChromosomes, report, resegment, resetSegments, sampleCNs, sampleName, sampleName<-, seqOfSegmentsByDP, setLocusData, setMeanEstimators, setPloidy, setSampleName, setSegments, shiftTCN, tileChromosomes, updateMeans, writeWIG \bold{Methods inherited from list}:\cr Ops,nonStructure,vector-method, Ops,structure,vector-method, Ops,vector,nonStructure-method, Ops,vector,structure-method, all.equal, as.data.frame, attachLocally, averageQuantile, callHooks, coerce,ANY,list-method, normalizeAverage, normalizeDifferencesToAverage, normalizeQuantileRank, normalizeQuantileSpline, plotDensity, relist, reset, type.convert, within } \author{Henrik Bengtsson} \seealso{ The \code{\link{segmentByNonPairedPSCBS}}() method returns an object of this class. } \keyword{classes} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/nbrOfSegments.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000002024�15000477031�017027� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{nbrOfSegments.AbstractCBS} \alias{nbrOfSegments.AbstractCBS} \alias{AbstractCBS.nbrOfSegments} \alias{nbrOfSegments,AbstractCBS-method} \title{Gets the number of segments} \description{ Gets the number of segments. } \usage{ \method{nbrOfSegments}{AbstractCBS}(this, splitters=FALSE, ...) } \arguments{ \item{splitters, ...}{Arguments passed to \code{\link[PSCBS:getSegments.AbstractCBS]{*getSegments}()}.} } \value{ Returns an \code{\link[base]{integer}}. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:nbrOfChangePoints.AbstractCBS]{*nbrOfChangePoints}()} \code{\link[PSCBS:nbrOfChromosomes.AbstractCBS]{*nbrOfChromosomes}()} For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callGainsAndLosses.CBS.Rd�����������������������������������������������������������������0000644�0001762�0000144�00000005637�15000477031�016315� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callGainsAndLosses.CBS} \alias{callGainsAndLosses.CBS} \alias{CBS.callGainsAndLosses} \alias{callGainsAndLosses,CBS-method} \title{Calls gains and losses} \description{ Calls gains and losses. } \usage{ \method{callGainsAndLosses}{CBS}(fit, adjust=1, method=c("ucsf-mad", "ucsf-dmad"), ..., verbose=FALSE) } \arguments{ \item{adjust}{A positive scale factor adjusting the sensitivity of the caller, where a value less (greater) than 1.0 makes the caller less (more) sensitive.} \item{method}{A \code{\link[base]{character}} string specifying the calling algorithm to use.} \item{...}{Additional/optional arguments used to override the default parameters used by the caller.} } \value{ Returns a \code{\link[PSCBS]{CBS}} object where \code{\link[base]{logical}} columns 'lossCall' and 'gainCall' have been appended to the segmentation table. } \section{The UCSF caller}{ If \code{method == "ucsf-mad"}, then segments are called using [1], i.e. a segment is called gained or lost if its segment level is at least two standard deviations away from the median segment level on Chr1-22, where standard deviation is estimated using MAD. Then same is done for \code{method == "ucsf-dmad"} with the difference that the standard deviation is estimated using a robust first order variance estimator. } \examples{ # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # CALLS # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Call gains and losses by segments fitC <- callGainsAndLosses(fit) # Call amplifications by segments fitC <- callAmplifications(fitC) # Call outliers by loci fitC <- callOutliers(fitC) } \author{Henrik Bengtsson} \references{ [1] Fridlyand et al. \emph{Breast tumor copy number aberration phenotypes and genomic instability}, BMC Cancer, 2006. \cr } \seealso{ \code{\link[PSCBS:callAmplifications.CBS]{*callAmplifications}()}. \code{\link[PSCBS:callOutliers.CBS]{*callOutliers}()}. For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������PSCBS/man/estimateDeltaCN.PairedPSCBS.Rd������������������������������������������������������������0000644�0001762�0000144�00000003173�15000477031�017173� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callCopyNeutral.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateDeltaCN.PairedPSCBS} \alias{estimateDeltaCN.PairedPSCBS} \alias{PairedPSCBS.estimateDeltaCN} \alias{estimateDeltaCN,PairedPSCBS-method} \alias{estimateDeltaCN} \alias{estimateDeltaCN.CBS} \title{Estimates the length of one total copy-number (TCN) unit} \description{ Estimates the length of one total copy-number (TCN) unit } \usage{ \method{estimateDeltaCN}{PairedPSCBS}(fit, scale=1, flavor=c("1-kappa", "delta(mode)"), kappa=estimateKappa(fit), adjust=0.2, quantile=0.95, ...) } \arguments{ \item{scale}{A \code{\link[base]{numeric}} scale factor in (0,Inf) used for rescaling (multiplying) the final estimate with.} \item{flavor}{Specifies which type of estimator should be used.} \item{kappa}{Estimate of background signal (used by the \code{"1-kappa"} method).} \item{adjust, quantile}{Tuning parameters (used by the \code{"delta(mode)"} method).} \item{...}{Not used.} } \value{ Returns a positive scalar \code{\link[base]{numeric}}. } \details{ For parent-specific copy-number (PSCN) data, the TCN unit length is estimated as \eqn{(1-kappa)/2}, where \eqn{kappa} is estimated from data (by \code{\link[PSCBS]{estimateKappa}}). For total copy-number (TCN) data (only), } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{PairedPSCBS}}. } \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/c.CBS.Rd����������������������������������������������������������������������������������0000644�0001762�0000144�00000001621�15000477031�013013� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.RESTRUCT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{c.CBS} \alias{c.CBS} \alias{CBS.c} \alias{c,CBS-method} \alias{c.PSCBS} \title{Concatenates segmentation results} \description{ Concatenates segmentation results. } \usage{ \method{c}{CBS}(..., addSplit=TRUE) } \arguments{ \item{\dots}{One or more \code{\link{AbstractCBS}} objects to be combined.} \item{addSplit}{If \code{\link[base:logical]{TRUE}}, a "divider" is added between chromosomes.} } \value{ Returns an \code{\link{AbstractCBS}} object of the same class in \dots. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������PSCBS/man/as.CBS.DNAcopy.Rd�������������������������������������������������������������������������0000644�0001762�0000144�00000002007�15000477031�014467� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{as.CBS.DNAcopy} \alias{as.CBS.DNAcopy} \alias{DNAcopy.as.CBS} \alias{as.CBS,DNAcopy-method} \title{Coerces a DNAcopy object to a CBS object} \description{ Coerces a DNAcopy object to a CBS object. } \usage{ \method{as.CBS}{DNAcopy}(fit, sample=1L, ...) } \arguments{ \item{fit}{A \code{\link[DNAcopy:DNAcopy]{DNAcopy}}. object (of the \pkg{DNAcopy} package.)} \item{sample}{An index specifying which sample to extract, if more than one exists.} \item{...}{Not used.} } \value{ Returns a \code{\link{CBS}} object. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:as.DNAcopy.CBS]{as.DNAcopy()}}. For more information see \code{\link[DNAcopy:DNAcopy]{DNAcopy}}. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getSegments.PSCBS.Rd����������������������������������������������������������������������0000644�0001762�0000144�00000002111�15000477031�015314� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getSegments.PSCBS} \alias{getSegments.PSCBS} \alias{PSCBS.getSegments} \alias{getSegments,PSCBS-method} \title{Gets the segments} \description{ Gets the segments. } \usage{ \method{getSegments}{PSCBS}(fit, simplify=FALSE, splitters=TRUE, addGaps=FALSE, ...) } \arguments{ \item{simplify}{If \code{\link[base:logical]{TRUE}}, redundant and intermediate information is dropped.}# \item{splitters}{If \code{\link[base:logical]{TRUE}}, "splitters" between chromosomes are preserved, otherwise dropped.} \item{...}{Not used.} } \value{ Returns a SxK \code{\link[base]{data.frame}}, where S in the number of segments, and K is the number of segment-specific fields. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{PSCBS}}. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/normalizeTotalCNs.AbstractCBS.Rd����������������������������������������������������������0000644�0001762�0000144�00000002050�15000477031�017662� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{normalizeTotalCNs.AbstractCBS} \alias{normalizeTotalCNs.AbstractCBS} \alias{AbstractCBS.normalizeTotalCNs} \alias{normalizeTotalCNs,AbstractCBS-method} \alias{normalizeTotalCNs} \alias{normalizeTotalCNs.PSCBS} \title{Normalizes copy numbers such that the whole-genome average total copy number is two} \description{ Normalizes copy numbers such that the whole-genome average total copy number is two. } \usage{ \method{normalizeTotalCNs}{AbstractCBS}(...) } \arguments{ \item{...}{Additional arguments passed to the normalization method.} } \value{ Returns a normalized AbstractCBS object of the same class as \code{fit}. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}.. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateKappaByC1Density.PairedPSCBS.Rd���������������������������������������������������0000644�0001762�0000144�00000006361�15000477031�020776� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateKappa.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateKappaByC1Density.PairedPSCBS} \alias{estimateKappaByC1Density.PairedPSCBS} \alias{PairedPSCBS.estimateKappaByC1Density} \alias{estimateKappaByC1Density,PairedPSCBS-method} \title{Estimate global background in segmented copy numbers} \description{ Estimate global background in segmented copy numbers based on the location of peaks in a weighted density estimator of the minor copy number mean levels. The global background, here called \eqn{\kappa}, may have multiple origins where normal contamination is one, but not necessarily the only one. \emph{Assumptions:} This estimator assumes that there are segments with C1=0 and C1=1, i.e. some deletions and, typically, some normal segements. } \usage{ \method{estimateKappaByC1Density}{PairedPSCBS}(this, typeOfWeights=c("dhNbrOfLoci", "sqrt(dhNbrOfLoci)"), adjust=1, from=0, minDensity=0.2, ..., verbose=FALSE) } \arguments{ \item{typeOfWeights}{A \code{\link[base]{character}} string specifying how weights are calculated.} \item{adjust}{A \code{\link[base]{numeric}} scale factor specifying the size of the bandwidth parameter used by the density estimator.} \item{from}{A \code{\link[base]{numeric}} scalar specifying the lower bound for the support of the estimated density.} \item{minDensity}{A non-negative \code{\link[base]{numeric}} threshold specifying the minimum density a peak should have in order to consider it a peak.} \item{...}{Not used.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the background estimate as a \code{\link[base]{numeric}} scalar. } \section{Algorithm}{ \itemize{ \item Retrieve segment-level minor copy numbers and corresponding weights: \enumerate{ \item Grabs the segment-level C1 estimates. \item Calculate segment weights. The default (\code{typeOfWeights="dhNbrOfLoci"}) is to use weights proportional to the number of heterozygous SNPs. An alternative (\code{typeOfWeights="sqrt(dhNbrOfLoci)"}) is to use the square root of those counts. } \item Identify subset of regions with C1=0: \enumerate{ \item Estimates the weighted empirical density function (truncated at zero below). Tuning parameter 'adjust'. \item Find the first two peaks (with a density greater than tuning parameter 'minDensity'). \item Assumes that the two peaks corresponds to C1=0 and C1=1. \item Defines threshold Delta0.5 as the center location between these two peaks. } \item Estimate the global background signal: \enumerate{ \item For all segments with C1 < Delta0.5, calculate the weighted median of their C1:s. \item Let kappa be the above weighted median. This is the estimated background. } } } \author{Henrik Bengtsson} \seealso{ Instead of calling this method explicitly, it is recommended to use the \code{\link[PSCBS:estimateKappa.PairedPSCBS]{*estimateKappa}()} method. } \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateDeltaLOH.PairedPSCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000003065�15000477031�017315� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateDeltaLOH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateDeltaLOH.PairedPSCBS} \alias{estimateDeltaLOH.PairedPSCBS} \alias{PairedPSCBS.estimateDeltaLOH} \alias{estimateDeltaLOH,PairedPSCBS-method} \title{Estimate a threshold for calling LOH from DH} \description{ Estimate a threshold for calling LOH from DH to be used by the \code{\link[PSCBS:callLOH.PairedPSCBS]{*callLOH}()} method. } \usage{ \method{estimateDeltaLOH}{PairedPSCBS}(this, flavor=c("minC1|nonAB"), ..., max=Inf, verbose=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of estimator to use.} \item{...}{Additional arguments passed to the estimator.} \item{max}{(Optional) The maximum estimate allowed. If greater than this value, the estimate will be truncated.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the threshold estimate as a \code{\link[base]{numeric}} scalar or -\code{\link[base:is.finite]{Inf}}. In case it is not possible to estimate the LOH threshold, then -\code{\link[base:is.finite]{Inf}} is returned. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:estimateDeltaLOHByMinC1ForNonAB.PairedPSCBS]{*estimateDeltaLOHByMinC1ForNonAB}()}. } \keyword{internal} \keyword{methods} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callCopyNeutralByTCNofAB.PairedPSCBS.Rd���������������������������������������������������0000644�0001762�0000144�00000003611�15000477031�020653� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callCopyNeutral.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callCopyNeutralByTCNofAB.PairedPSCBS} \alias{callCopyNeutralByTCNofAB.PairedPSCBS} \alias{PairedPSCBS.callCopyNeutralByTCNofAB} \alias{callCopyNeutralByTCNofAB,PairedPSCBS-method} \title{Calls regions that are copy neutral} \description{ Calls regions that are copy neutral from the total copy numbers (TCNs) of segments in allelic balance (AB). } \usage{ \method{callCopyNeutralByTCNofAB}{PairedPSCBS}(fit, delta=estimateDeltaCN(fit), alpha=0.05, ..., force=FALSE, verbose=FALSE) } \arguments{ \item{fit}{A PairedPSCBS fit object as returned by \code{\link[PSCBS]{segmentByPairedPSCBS}}.} \item{delta}{A non-negative \code{\link[base]{double}} specifying the width of the "acceptance" region. Defaults to half of the distance between two integer TCN states, i.e. 1/2. This argument should be shrunken as a function of the amount of the normal contamination and other background signals.} \item{alpha}{A \code{\link[base]{double}} in [0,0.5] specifying the significance level of the confidence intervals used.} \item{...}{Additional arguments passed to \code{\link[PSCBS:calcStatsForCopyNeutralABs.PairedPSCBS]{*calcStatsForCopyNeutralABs}()}.} \item{force}{If \code{\link[base:logical]{TRUE}}, an already called object is skipped, otherwise not.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link{PairedPSCBS}} fit object where a column with the copy-neutral call. } \details{ ... } %% examples "../incl/callCopyNeutralByTCNofAB.PairedPSCBS.Rex" \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} �����������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateDeltaAB.PairedPSCBS.Rd������������������������������������������������������������0000644�0001762�0000144�00000003446�15000477031�017160� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.estimateDeltaAB.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateDeltaAB.PairedPSCBS} \alias{estimateDeltaAB.PairedPSCBS} \alias{PairedPSCBS.estimateDeltaAB} \alias{estimateDeltaAB,PairedPSCBS-method} \title{Estimate a threshold for calling allelic balance from DH} \description{ Estimate a threshold for calling allelic balance from DH to be used by the \code{\link[PSCBS:callAB.PairedPSCBS]{*callAB}()} method. } \usage{ \method{estimateDeltaAB}{PairedPSCBS}(this, scale=NULL, flavor=c("qq(DH)", "q(DH)", "mad(hBAF)", "median(DH)"), ..., max=Inf, verbose=FALSE) } \arguments{ \item{scale}{An optional \code{\link[base]{numeric}} scale factor.} \item{flavor}{A \code{\link[base]{character}} string specifying which type of estimator to use.} \item{...}{Additional arguments passed to the estimator.} \item{max}{(Optional) The maximum estimate allowed. If greater than this value, the estimate will be truncated.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the threshold estimate as a \code{\link[base]{numeric}} scalar. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:estimateDeltaABBySmallDH.PairedPSCBS]{*estimateDeltaABBySmallDH}()}, \code{\link[PSCBS:estimateStdDevForHeterozygousBAF.PairedPSCBS]{*estimateStdDevForHeterozygousBAF}()}, \code{\link[PSCBS:estimateMeanForDH.PairedPSCBS]{*estimateMeanForDH}()}, and \code{\link[PSCBS:estimateHighDHQuantileAtAB.PairedPSCBS]{*estimateHighDHQuantileAtAB}()}. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callCopyNeutral.PairedPSCBS.Rd������������������������������������������������������������0000644�0001762�0000144�00000003246�15000477031�017267� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callCopyNeutral.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callCopyNeutral.PairedPSCBS} \alias{callCopyNeutral.PairedPSCBS} \alias{PairedPSCBS.callCopyNeutral} \alias{callCopyNeutral,PairedPSCBS-method} \alias{PairedPSCBS.callNTCN} \alias{callNTCN.PairedPSCBS} \alias{callNTCN,PairedPSCBS-method} \title{Calls segments that have a neutral total copy number} \description{ Calls segments that have a neutral total copy number (NTCN), i.e. that have a TCN that corresponds to the ploidy of the genome. } \usage{ \method{callCopyNeutral}{PairedPSCBS}(fit, flavor=c("TCN|AB"), ..., minSize=1, force=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of call to use.} \item{...}{Additional arguments passed to the caller.} \item{minSize}{An optional \code{\link[base]{integer}} specifying the minimum number of data points in order to call a segments. If fewer data points, then the call is set to \code{\link[base]{NA}} regardless.} \item{force}{If \code{\link[base:logical]{FALSE}}, and copy-neutral calls already exits, then nothing is done, otherwise the calls are done.} } \value{ Returns a \code{\link{PairedPSCBS}} object with copy-neutral calls. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{\link[PSCBS:callCopyNeutralByTCNofAB.PairedPSCBS]{*callCopyNeutralByTCNofAB}()}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callOutliers.CBS.Rd�����������������������������������������������������������������������0000644�0001762�0000144�00000003626�15000477031�015242� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.CALL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callOutliers.CBS} \alias{callOutliers.CBS} \alias{CBS.callOutliers} \alias{callOutliers,CBS-method} \title{Calls outliers} \description{ Calls outliers. } \usage{ \method{callOutliers}{CBS}(fit, adjust=1, method=c("ucsf-mad"), ...) } \arguments{ \item{adjust}{A positive scale factor adjusting the sensitivity of the caller, where a value less (greater) than 1.0 makes the caller less (more) sensitive.} \item{method}{A \code{\link[base]{character}} string specifying the calling algorithm to use.} \item{...}{Additional/optional arguments used to override the default parameters used by the caller.} } \value{ Returns a \code{\link[PSCBS]{CBS}} object where \code{\link[base]{logical}} columns 'negOutlierCall' and 'posOutlierCall' have been appended to the segmentation table. } \section{The UCSF caller}{ If \code{method == "ucsf-mad"}, then loci are called using [1] "Finally, to identify single technical or biological outliers such as high level amplifications, the presence of the outliers within a segment was allowed by assigning the original observed log2ratio to the clones for which the observed values were more than four tumor-specific MAD away from the smoothed values." [1; Suppl. Mat.] } \author{Henrik Bengtsson} \references{ [1] Fridlyand et al. \emph{Breast tumor copy number aberration phenotypes and genomic instability}, BMC Cancer, 2006. \cr } \seealso{ \code{\link[PSCBS:callGainsAndLosses.CBS]{*callGainsAndLosses}()}. \code{\link[PSCBS:callAmplifications.CBS]{*callAmplifications}()}. For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������PSCBS/man/segmentByNonPairedPSCBS.Rd����������������������������������������������������������������0000644�0001762�0000144�00000015664�15000477031�016527� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % segmentByNonPairedPSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{segmentByNonPairedPSCBS} \alias{segmentByNonPairedPSCBS.default} \alias{segmentByNonPairedPSCBS} \alias{segmentByNonPairedPSCBS.data.frame} \alias{segmentByNonPairedPSCBS.PairedPSCBS} \alias{segmentByNonPairedPSCBS} \title{Segment total copy numbers and allele B fractions using the Non-paired PSCBS method} \description{ Segment total copy numbers and allele B fractions using the Non-paired PSCBS method [1]. This method does not requires matched normals. This is a low-level segmentation method. It is intended to be applied to one tumor sample at the time. } \usage{ \method{segmentByNonPairedPSCBS}{default}(CT, betaT, ..., flavor=c("tcn", "tcn&dh", "tcn,dh", "sqrt(tcn),dh", "sqrt(tcn)&dh"), tauA=NA, tauB=1 - tauA, verbose=FALSE) } \arguments{ \item{CT}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J tumor total copy number (TCN) ratios in [0,+\code{\link[base:is.finite]{Inf}}) (due to noise, small negative values are also allowed). The TCN ratios are typically scaled such that copy-neutral diploid loci have a mean of two.} \item{betaT}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J tumor allele B fractions (BAFs) in [0,1] (due to noise, values may be slightly outside as well) or \code{\link[base]{NA}} for non-polymorphic loci.} \item{...}{Additional arguments passed to \code{\link{segmentByPairedPSCBS}}().} \item{flavor}{A \code{\link[base]{character}} specifying what type of segmentation and calling algorithm to be used.} \item{tauA, tauB}{Lower and upper thresholds (\code{tauA < tauB} for calling SNPs heterozygous based on the tumor allele B fractions (\code{betaT}). If \code{\link[base]{NA}}, then they are estimates from data. } \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns the segmentation results as a \code{\link{NonPairedPSCBS}} object. } \details{ Internally \code{\link{segmentByPairedPSCBS}}() is used for segmentation. This segmentation method does \emph{not} support weights. } \section{Reproducibility}{ The "DNAcopy::segment" implementation of CBS uses approximation through random sampling for some estimates. Because of this, repeated calls using the same signals may result in slightly different results, unless the random seed is set/fixed. } \section{Whole-genome segmentation is preferred}{ Although it is possible to segment each chromosome independently using Paired PSCBS, we strongly recommend to segment whole-genome (TCN,BAF) data at once. The reason for this is that downstream CN-state calling methods, such as the AB and the LOH callers, performs much better on whole-genome data. In fact, they may fail to provide valid calls if done chromosome by chromosome. } \section{Missing and non-finite values}{ The total copy number signals as well as any optional positions must not contain missing values, i.e. \code{\link[base]{NA}}s or \code{\link[base:is.finite]{NaN}}s. If there are any, an informative error is thrown. Allele B fractions may contain missing values, because such are interpreted as representing non-polymorphic loci. None of the input signals may have infinite values, i.e. -\code{\link[base:is.finite]{Inf}} or +\code{\link[base:is.finite]{Inf}}. If so, an informative error is thrown. } \section{Non-Paired PSCBS with known genotypes}{ If allele B fractions for the matched normal (\code{betaN}) are not available, but genotypes (\code{muN}) are, then it is possible to run Paired PSCBS. See \code{\link{segmentByPairedPSCBS}}() for details. } \examples{ verbose <- R.utils::Arguments$getVerbose(-10*interactive(), timestamp=TRUE) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Load SNP microarray data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - data <- PSCBS::exampleData("paired.chr01") str(data) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Paired PSCBS segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Drop single-locus outliers dataS <- dropSegmentationOutliers(data) # Speed up example by segmenting fewer loci dataS <- dataS[seq(from=1, to=nrow(data), by=20),] str(dataS) R.oo::attachLocally(dataS) # Non-Paired PSCBS segmentation fit <- segmentByNonPairedPSCBS(CT, betaT=betaT, chromosome=chromosome, x=x, seed=0xBEEF, verbose=verbose) print(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Bootstrap segment level estimates # (used by the AB caller, which, if skipped here, # will do it automatically) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- bootstrapTCNandDHByRegion(fit, B=100, verbose=verbose) print(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in allelic balance (AB) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in DH for calling AB # (which be done by default by the caller, if skipped here) deltaAB <- estimateDeltaAB(fit, flavor="qq(DH)", verbose=verbose) print(deltaAB) fit <- callAB(fit, delta=deltaAB, verbose=verbose) print(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaAB == deltaAB) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Calling segments in loss-of-heterozygosity (LOH) # NOTE: Ideally, this should be done on whole-genome data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Explicitly estimate the threshold in C1 for calling LOH # (which be done by default by the caller, if skipped here) deltaLOH <- estimateDeltaLOH(fit, flavor="minC1|nonAB", verbose=verbose) print(deltaLOH) fit <- callLOH(fit, delta=deltaLOH, verbose=verbose) print(fit) plotTracks(fit) # Even if not explicitly specified, the estimated # threshold parameter is returned by the caller stopifnot(fit$params$deltaLOH == deltaLOH) } \author{Henrik Bengtsson} \references{ [1] A.B. Olshen, H. Bengtsson, P. Neuvial, P.T. Spellman, R.A. Olshen, V.E. Seshan, \emph{Parent-specific copy number in paired tumor-normal studies using circular binary segmentation}, Bioinformatics, 2011 \cr [2] H. Bengtsson, P. Neuvial and T.P. Speed, \emph{TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays}, BMC Bioinformatics, 2010 \cr } \seealso{ To segment paired tumor-normal total copy numbers and allele B fractions, see \code{\link{segmentByPairedPSCBS}}(). To segment total copy numbers, or any other unimodal signals, see \code{\link{segmentByCBS}}(). } \keyword{IO} ����������������������������������������������������������������������������PSCBS/man/randomSeed.Rd�����������������������������������������������������������������������������0000644�0001762�0000144�00000002575�15000477031�014255� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % randomSeed.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{randomSeed} \alias{randomSeed} \title{Sets and resets the .Random.seed in the global environment} \description{ Sets and resets the .Random.seed in the global environment. } \usage{ randomSeed(action=c("set", "advance", "reset", "get"), seed=NULL, kind=NULL, n=1L, backup=TRUE) } \arguments{ \item{action}{A \code{\link[base]{character}} string specifying the action.} \item{seed}{Random seed to be set; only for \code{action="set"}. If \code{length(seed) == 1}, then \code{set.seed(seed)} is used, otherwise \code{.Random.seed} is assigned the value.} \item{kind}{(optional) A \code{\link[base]{character}} string specifying type of random number generator to use, cf. \code{\link[base]{RNGkind}}().} \item{n}{Number of random seeds to generate by \code{action}.} \item{backup}{If \code{\link[base:logical]{TRUE}}, the previous (seed, kind) state is recorded such that it can be reset later.} } \value{ Returns a \code{.Random.seed}. If more than one is returned, the they are returned as a \code{\link[base]{list}}. } \author{Henrik Bengtsson} \keyword{internal} �����������������������������������������������������������������������������������������������������������������������������������PSCBS/man/pruneBySdUndo.CBS.Rd����������������������������������������������������������������������0000644�0001762�0000144�00000005257�15000477031�015343� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.PRUNE.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{pruneBySdUndo.CBS} \alias{pruneBySdUndo.CBS} \alias{CBS.pruneBySdUndo} \alias{pruneBySdUndo,CBS-method} \title{Prune the CBS profile by dropping change points that are too small} \description{ Prune the CBS profile by dropping change points that are too small, where "too small" means that the amplitude of the change points is less than a multiple of the overall standard deviation of the copy-number signals. } \usage{ \method{pruneBySdUndo}{CBS}(fit, rho=3, sigma="DNAcopy", ..., verbose=FALSE) } \arguments{ \item{fit}{A \code{\link{CBS}} object.} \item{rho}{A positive \code{\link[base]{double}} scalar specifying the number of standard deviations (\code{rho*sigma}) required in order to keep a change point. More change points are dropped the greater this value is.} \item{sigma}{The whole-genome standard deviation of the locus-level copy number signals. The default is to calculate it from the data and as done in the \pkg{DNAcopy} package.} \item{...}{(Optional) Additional arguments passed to the standard deviation estimator function.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link{CBS}} object (of the same class as \code{fit}). } \details{ This method corresponds to using the \code{undo} argument when calling \code{\link{segmentByCBS}}(), which in turn corresponds to using the \code{undo.splits="sdundo"} and \code{undo.SD} of the underlying \code{\link[DNAcopy]{segment}} method. } \examples{ # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Simulating copy-number data # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - set.seed(0xBEEF) # Number of loci J <- 1000 mu <- double(J) mu[1:100] <- mu[1:100] + 0.3 mu[200:300] <- mu[200:300] + 1 mu[350:400] <- NA # centromere mu[650:800] <- mu[650:800] - 1 eps <- rnorm(J, sd=1/2) y <- mu + eps x <- sort(runif(length(y), max=length(y))) * 1e5 w <- runif(J) w[650:800] <- 0.001 # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Segmentation # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fit <- segmentByCBS(y, x=x) print(fit) plotTracks(fit) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Post-segmentation pruning # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - fitP <- pruneBySdUndo(fit, rho=1) drawLevels(fitP, col="red") } \author{Henrik Bengtsson, Pierre Neuvial} \keyword{internal} \keyword{methods} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/estimateStandardDeviation.CBS.Rd����������������������������������������������������������0000644�0001762�0000144�00000003130�15000477031�017725� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.EXTS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{estimateStandardDeviation.CBS} \alias{estimateStandardDeviation.CBS} \alias{CBS.estimateStandardDeviation} \alias{estimateStandardDeviation,CBS-method} \title{Estimates the whole-genome standard deviation of the signals} \description{ Estimates the whole-genome standard deviation of the signals. } \usage{ \method{estimateStandardDeviation}{CBS}(fit, chromosomes=NULL, method=c("diff", "res", "abs", "DNAcopy"), estimator=c("mad", "sd"), na.rm=TRUE, weights=NULL, ...) } \arguments{ \item{chromosomes}{An optional \code{\link[base]{vector}} specifying the subset of chromosomes used for the estimate. If \code{\link[base]{NULL}}, all chromosomes are used.} \item{method}{A \code{\link[base]{character}} string specifying the method used.} \item{estimator}{A \code{\link[base]{character}} string or a \code{\link[base]{function}} specifying the internal estimator.} \item{na.rm}{If \code{\link[base:logical]{TRUE}}, missing values are dropped, otherwise not.} \item{weights}{An optional \code{\link[base]{double}} \code{\link[base]{vector}} of \code{nbrOfLoci()} non-negative weights.} \item{...}{Not used.} } \value{ Returns a non-negative \code{\link[base]{numeric}} scale. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{CBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/plotTracks1.PairedPSCBS.Rd����������������������������������������������������������������0000644�0001762�0000144�00000006121�15000477031�016370� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.PLOT.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{plotTracks1.PairedPSCBS} \alias{plotTracks1.PairedPSCBS} \alias{PairedPSCBS.plotTracks1} \alias{plotTracks1,PairedPSCBS-method} \alias{PairedPSCBS.plotTracks} \alias{plotTracks.PairedPSCBS} \alias{plotTracks,PairedPSCBS-method} \alias{PairedPSCBS.plotTracks2} \alias{plotTracks2.PairedPSCBS} \alias{plotTracks2,PairedPSCBS-method} \alias{PairedPSCBS.plotTracksManyChromosomes} \alias{plotTracksManyChromosomes.PairedPSCBS} \alias{plotTracksManyChromosomes,PairedPSCBS-method} \alias{plot} \title{Plots parental specific copy numbers along the genome} \description{ Plots parental specific copy numbers along the genome for one or more chromosomes. It is possible to specify what type of tracks to plot. Each type of track is plotted in its own panel. } \usage{ \method{plotTracks1}{PairedPSCBS}(x, tracks=c("tcn", "dh", "tcn,c1,c2", "tcn,c1", "tcn,c2", "c1,c2", "betaN", "betaT", "betaTN")[1:3], scatter="*", calls=".*", pch=".", col=NULL, cex=1, changepoints=FALSE, grid=FALSE, quantiles=c(0.05, 0.95), xlim=NULL, Clim=c(0, 3 * ploidy(x)), Blim=c(0, 1), xScale=1e-06, ..., add=FALSE, subplots=!add && (length(tracks) > 1), verbose=FALSE) } \arguments{ \item{x}{A result object returned by \code{\link{segmentByPairedPSCBS}}().} \item{tracks}{A \code{\link[base]{character}} \code{\link[base]{vector}} specifying what types of tracks to plot.} \item{scatter}{A \code{\link[base]{character}} \code{\link[base]{vector}} specifying which of the tracks should have scatter plot.} \item{calls}{A \code{\link[base]{character}} \code{\link[base]{vector}} of regular expression identifying call labels to be highlighted in the panels.} \item{pch}{The type of the scatter points, if any.} \item{col}{The color of the scatter points, if any.} \item{cex}{The size of the scatter points, if any.} \item{changepoints}{If \code{\link[base:logical]{TRUE}}, changepoints are drawn as vertical lines.} \item{grid}{If \code{\link[base:logical]{TRUE}}, horizontal lines are displayed.} \item{quantiles}{A \code{\link[base]{numeric}} \code{\link[base]{vector}} in [0,1] specifying the quantiles of the confidence bands to be drawn, if any.} \item{xlim}{(Optional) The genomic range to plot.} \item{Clim}{The range of copy numbers.} \item{Blim}{The range of allele B fractions (BAFs) and decrease of heterozygosity (DHs).} \item{xScale}{The scale factor used for genomic positions.} \item{...}{Not used.} \item{add}{If \code{\link[base:logical]{TRUE}}, the panels plotted are added to the existing plot, otherwise a new plot is created.} \item{subplots}{If \code{\link[base:logical]{TRUE}}, then subplots are automatically setup.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns nothing. } \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} \keyword{IO} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/writeSegments.CBS.Rd����������������������������������������������������������������������0000644�0001762�0000144�00000003074�15000477031�015435� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.IO.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{writeSegments.CBS} \alias{writeSegments.CBS} \alias{CBS.writeSegments} \alias{writeSegments,CBS-method} \alias{writeWIG} \alias{writeWIG.AbstractCBS} \title{Writes the table of segments to file} \description{ Writes the table of segments to file. } \usage{ \method{writeSegments}{CBS}(fit, name=getSampleName(fit), tags=NULL, ext="tsv", path=NULL, addHeader=TRUE, createdBy=NULL, sep="\t", nbrOfDecimals=4L, splitters=FALSE, overwrite=FALSE, skip=FALSE, ...) } \arguments{ \item{name, tags}{Name and optional tags part of the filename}. \item{path}{The directory where the file will be written.} \item{addHeader}{If \code{\link[base:logical]{TRUE}}, header comments are written.} \item{createdBy}{A header comment of whom created the file.} \item{splitters}{If \code{\link[base:logical]{TRUE}}, each chromosome is separated by a row of missing values.} \item{overwrite, skip}{If an output file already exists, these arguments specifies what should happen.} \item{...}{Additional arguments pass to \code{getSegments()}.} } \value{ Returns the pathname of the the file written. } \author{Henrik Bengtsson} \seealso{ Utilizes \code{\link[PSCBS:getSegments.CBS]{*getSegments}()}. For more information see \code{\link{CBS}}.. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/ploidy.AbstractCBS.Rd���������������������������������������������������������������������0000644�0001762�0000144�00000002542�15000477031�015560� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{ploidy.AbstractCBS} \alias{ploidy.AbstractCBS} \alias{AbstractCBS.ploidy} \alias{ploidy,AbstractCBS-method} \alias{AbstractCBS.ploidy<-} \alias{ploidy<-.AbstractCBS} \alias{ploidy<-,AbstractCBS-method} \alias{AbstractCBS.setPloidy} \alias{setPloidy.AbstractCBS} \alias{setPloidy,AbstractCBS-method} \alias{AbstractCBS.adjustPloidyScale} \alias{adjustPloidyScale.AbstractCBS} \alias{adjustPloidyScale,AbstractCBS-method} \alias{adjustPloidyScale.PairedPSCBS} \alias{adjustPloidyScale} \alias{ploidy} \alias{ploidy<-} \alias{setPloidy} \title{Gets and sets ploidy} \description{ Gets and sets ploidy. } \usage{ \method{ploidy}{AbstractCBS}(fit, ...) \method{ploidy}{AbstractCBS}(fit) <- value } \arguments{ \item{fit}{An \code{\link{AbstractCBS}} object.} \item{value}{An \code{\link[base]{integer}} (in \eqn{1,2,\ldots}) specifying the genome ploidy .} \item{...}{Not used.} } \value{ Returns (invisibly) an updated object. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}.. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/gapsToSegments.data.frame.Rd��������������������������������������������������������������0000644�0001762�0000144�00000003015�15000477031�017126� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % gapsToSegments.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{gapsToSegments.data.frame} \alias{gapsToSegments.data.frame} \alias{gapsToSegments} \title{Gets the genomic segments that are complementary to the gaps} \description{ Gets the genomic segments that are complementary to the gaps, with default chromosome boundaries being \code{-Inf} and \code{+Inf}. } \usage{ \method{gapsToSegments}{data.frame}(gaps, resolution=1L, minLength=0L, dropGaps=FALSE, ...) } \arguments{ \item{gaps}{A \code{\link[base]{data.frame}} with columns \code{chromosome}, \code{start}, and \code{stop}. Any overlapping gaps will throw an error.} \item{resolution}{A non-negative \code{\link[base]{numeric}} specifying the minimum length unit, which by default equals one nucleotide/base pair.} \item{minLength}{Minimum length of segments to be kept.} \item{dropGaps}{If \code{\link[base:logical]{TRUE}}, the gaps themselves are not part of the output.} \item{...}{Not used.} } \value{ Returns \code{\link[base]{data.frame}} of least one row with columns \code{chromosome} if that argument is given), \code{start}, \code{stop} and \code{length}. The segments are ordered along the genome. } \author{Henrik Bengtsson} \seealso{ \code{\link{findLargeGaps}}(). } \keyword{methods} \keyword{IO} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/updateMeansTogether.AbstractCBS.Rd��������������������������������������������������������0000644�0001762�0000144�00000002064�15000477031�020227� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.HCLUST.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{updateMeansTogether.AbstractCBS} \alias{updateMeansTogether.AbstractCBS} \alias{AbstractCBS.updateMeansTogether} \alias{updateMeansTogether,AbstractCBS-method} \alias{updateMeansTogether.CBS} \alias{updateMeansTogether.PairedPSCBS} \title{Updates the CN mean levels jointly in sets of segments} \description{ Updates the CN mean levels jointly in sets of segments as if they were one large segment. The locus-level data is not updated/modified. } \usage{ \method{updateMeansTogether}{AbstractCBS}(...) } \arguments{ \item{...}{Not used.} } \value{ Returns an object of the same class. } \author{Henrik Bengtsson} \seealso{ This method is utilized by \code{\link[PSCBS:pruneByHClust.AbstractCBS]{*pruneByHClust}()}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/testROH.numeric.Rd������������������������������������������������������������������������0000644�0001762�0000144�00000003307�15000477031�015157� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % testROH.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{testROH.numeric} \alias{testROH.numeric} \title{Tests if a segment is in Run-of-Homozygosity (ROH)} \description{ Tests if a segment is in Run-of-Homozygosity (ROH). } \usage{ \method{testROH}{numeric}(muN, csN=NULL, betaN=NULL, minNbrOfSnps=1, delta=1/12, ..., verbose=FALSE) } \arguments{ \item{muN}{An \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genotype calls in \{0,1/2,1\} for AA, AB, and BB, respectively, and \code{\link[base]{NA}} for non-polymorphic loci.} \item{csN}{(optional) A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J genotype confidence scores. If \code{\link[base]{NULL}}, ad hoc scores calculated from \code{betaN} are used.} \item{betaN}{(optional) A \code{\link[base]{numeric}} \code{\link[base]{vector}} of J matched normal BAFs in [0,1] (due to noise, values may be slightly outside as well) or \code{\link[base]{NA}} for non-polymorphic loci.} \item{minNbrOfSnps}{Minimum number of SNPs required to test segment. If not tested, \code{\link[base]{NA}} is returned.} \item{delta}{A \code{\link[base]{double}} scalar specifying the maximum (weighted) proportion of heterozygous SNPs allowed in an ROH region.} \item{...}{Not used.} \item{verbose}{See \code{\link[R.utils]{Verbose}}.} } \value{ Returns a \code{\link[base]{logical}}. } \author{Pierre Neuvial, Henrik Bengtsson} \keyword{methods} \keyword{internal} �������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/nbrOfChromosomes.AbstractCBS.Rd�����������������������������������������������������������0000644�0001762�0000144�00000001706�15000477031�017546� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{nbrOfChromosomes.AbstractCBS} \alias{nbrOfChromosomes.AbstractCBS} \alias{AbstractCBS.nbrOfChromosomes} \alias{nbrOfChromosomes,AbstractCBS-method} \title{Gets the number of chromosomes} \description{ Gets the number of chromosomes. } \usage{ \method{nbrOfChromosomes}{AbstractCBS}(this, ...) } \arguments{ \item{...}{Arguments passed to \code{\link[PSCBS:getChromosomes.AbstractCBS]{*getChromosomes}()}.} } \value{ Returns an \code{\link[base]{integer}}. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:getChromosomes.AbstractCBS]{*getChromosomes}()}. For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������PSCBS/man/PairedPSCBS.Rd����������������������������������������������������������������������������0000644�0001762�0000144�00000010021�15000477031�014154� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{PairedPSCBS} \docType{class} \alias{PairedPSCBS} \title{The PairedPSCBS class} \description{ Package: PSCBS \cr \bold{Class PairedPSCBS}\cr \code{list}\cr \code{~~|}\cr \code{~~+--}\code{\link[PSCBS]{AbstractCBS}}\cr \code{~~~~~~~|}\cr \code{~~~~~~~+--}\code{\link[PSCBS]{PSCBS}}\cr \code{~~~~~~~~~~~~|}\cr \code{~~~~~~~~~~~~+--}\emph{\code{PairedPSCBS}}\cr \bold{Directly known subclasses:}\cr \cr public abstract class \bold{PairedPSCBS}\cr extends \emph{\link[PSCBS]{PSCBS}}\cr A PairedPSCBS is an object containing the results from the Paired PSCBS method. } \usage{PairedPSCBS(fit=list(), ...)} \arguments{ \item{fit}{A \code{\link[base]{list}} structure containing the Paired PSCBS results.} \item{...}{Not used.} } \section{Fields and Methods}{ \bold{Methods:}\cr \tabular{rll}{ \tab \code{\link[PSCBS:callAB.PairedPSCBS]{callAB}} \tab Calls segments that are in allelic balance.\cr \tab \code{\link[PSCBS:callCopyNeutral.PairedPSCBS]{callCopyNeutral}} \tab Calls segments that have a neutral total copy number.\cr \tab \code{\link[PSCBS:callGNL.PairedPSCBS]{callGNL}} \tab Calls segments that are gained, copy neutral, or lost.\cr \tab \code{callGNLByTCNofAB} \tab -\cr \tab \code{callGainNeutralLoss} \tab -\cr \tab \code{\link[PSCBS:callLOH.PairedPSCBS]{callLOH}} \tab Calls segments that are in LOH.\cr \tab \code{callNTCN} \tab -\cr \tab \code{\link[PSCBS:callROH.PairedPSCBS]{callROH}} \tab Calls segments that are in ROH.\cr \tab \code{\link[PSCBS:estimateDeltaAB.PairedPSCBS]{estimateDeltaAB}} \tab Estimate a threshold for calling allelic balance from DH.\cr \tab \code{\link[PSCBS:estimateDeltaLOH.PairedPSCBS]{estimateDeltaLOH}} \tab Estimate a threshold for calling LOH from DH.\cr \tab \code{\link[PSCBS:estimateKappa.PairedPSCBS]{estimateKappa}} \tab Estimate global background in segmented copy numbers.\cr \tab \code{extractCNs} \tab -\cr \tab \code{hasBootstrapSummaries} \tab -\cr \tab \code{plotTracks} \tab -\cr \tab \code{segmentByNonPairedPSCBS} \tab -\cr \tab \code{segmentByPairedPSCBS} \tab -\cr \tab \code{seqOfSegmentsByDP} \tab -\cr } \bold{Methods inherited from PSCBS}:\cr as.data.frame, c, drawChangePoints, extractChromosomes, extractWIG, getLocusData, getLocusSignalNames, getSegmentTrackPrefixes, isLocallyPhased, isSegmentSplitter, normalizeTotalCNs, writeSegments \bold{Methods inherited from AbstractCBS}:\cr adjustPloidyScale, all.equal, as.data.frame, clearCalls, drawChangePoints, drawKnownSegments, dropChangePoint, dropChangePoints, dropRegion, dropRegions, extractCNs, extractChromosome, extractChromosomes, extractRegions, extractSegments, extractWIG, getChangePoints, getChromosomeOffsets, getChromosomeRanges, getChromosomes, getLocusData, getLocusSignalNames, getMeanEstimators, getSampleName, getSegmentSizes, getSegmentTrackPrefixes, getSegments, mergeThreeSegments, mergeTwoSegments, nbrOfChangePoints, nbrOfChromosomes, nbrOfLoci, nbrOfSegments, normalizeTotalCNs, ploidy, ploidy<-, plotTracks, print, pruneByDP, pruneByHClust, renameChromosomes, report, resegment, resetSegments, sampleCNs, sampleName, sampleName<-, seqOfSegmentsByDP, setLocusData, setMeanEstimators, setPloidy, setSampleName, setSegments, shiftTCN, tileChromosomes, updateMeans, writeWIG \bold{Methods inherited from list}:\cr Ops,nonStructure,vector-method, Ops,structure,vector-method, Ops,vector,nonStructure-method, Ops,vector,structure-method, all.equal, as.data.frame, attachLocally, averageQuantile, callHooks, coerce,ANY,list-method, normalizeAverage, normalizeDifferencesToAverage, normalizeQuantileRank, normalizeQuantileSpline, plotDensity, relist, reset, type.convert, within } \author{Henrik Bengtsson} \seealso{ The \code{\link{segmentByPairedPSCBS}}() method returns an object of this class. } \keyword{classes} ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/callGNL.PairedPSCBS.Rd��������������������������������������������������������������������0000644�0001762�0000144�00000003626�15000477031�015444� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callGNL.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callGNL.PairedPSCBS} \alias{callGNL.PairedPSCBS} \alias{PairedPSCBS.callGNL} \alias{callGNL,PairedPSCBS-method} \alias{PairedPSCBS.callGainNeutralLoss} \alias{callGainNeutralLoss.PairedPSCBS} \alias{callGainNeutralLoss,PairedPSCBS-method} \alias{callGNLByTCNofAB} \alias{PairedPSCBS.callGNLByTCNofAB} \alias{callGNLByTCNofAB.PairedPSCBS} \alias{callGNLByTCNofAB,PairedPSCBS-method} \alias{callGNLByTCNofABv1} \alias{PairedPSCBS.callGNLByTCNofABv1} \alias{callGNLByTCNofABv1.PairedPSCBS} \alias{callGNLByTCNofABv1,PairedPSCBS-method} \title{Calls segments that are gained, copy neutral, or lost} \description{ Calls segments that are gained, copy neutral, or lost, where copy neutral means having a total copy number that corresponds to the ploidy of the genome. } \usage{ \method{callGNL}{PairedPSCBS}(fit, flavor=c("TCN|AB"), ..., minSize=1, force=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of call to use.} \item{...}{Additional arguments passed to the caller.} \item{minSize}{An optional \code{\link[base]{integer}} specifying the minimum number of data points in order to call a segments. If fewer data points, then the call is set to \code{\link[base]{NA}} regardless.} \item{force}{If \code{\link[base:logical]{FALSE}}, and copy-neutral calls already exits, then nothing is done, otherwise the calls are done.} } \value{ Returns a \code{\link{PairedPSCBS}} object with added calls. } \author{Henrik Bengtsson} \seealso{ Internally, one of the following methods are used: \code{callGNLByTCNofAB()}. } \keyword{internal} \keyword{methods} ����������������������������������������������������������������������������������������������������������PSCBS/man/CBS.Rd������������������������������������������������������������������������������������0000644�0001762�0000144�00000006405�15000477031�012577� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % CBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{CBS} \docType{class} \alias{CBS} \title{The CBS class} \description{ A CBS object holds results from the Circular Binary Segmentation (CBS) method for \emph{one} sample for one or more chromosomes. Package: PSCBS \cr \bold{Class CBS}\cr \code{list}\cr \code{~~|}\cr \code{~~+--}\code{\link[PSCBS]{AbstractCBS}}\cr \code{~~~~~~~|}\cr \code{~~~~~~~+--}\emph{\code{CBS}}\cr \bold{Directly known subclasses:}\cr \cr public abstract class \bold{CBS}\cr extends \emph{\link[PSCBS]{AbstractCBS}}\cr } \usage{ CBS(...) } \arguments{ \item{...}{Arguments passed to the constructor of \code{\link{AbstractCBS}}.} } \section{Fields and Methods}{ \bold{Methods:}\cr \tabular{rll}{ \tab \code{as} \tab -\cr \tab \code{\link[PSCBS:c.CBS]{c}} \tab Concatenates segmentation results.\cr \tab \code{\link[PSCBS:estimateStandardDeviation.CBS]{estimateStandardDeviation}} \tab Estimates the whole-genome standard deviation of the signals.\cr \tab \code{\link[PSCBS:plotTracks.CBS]{plotTracks}} \tab Plots copy numbers along the genome.\cr \tab \code{\link[PSCBS:pruneBySdUndo.CBS]{pruneBySdUndo}} \tab Prune the CBS profile by dropping change points that are too small.\cr \tab \code{segmentByCBS} \tab -\cr \tab \code{seqOfSegmentsByDP} \tab -\cr \tab \code{\link[PSCBS:writeSegments.CBS]{writeSegments}} \tab Writes the table of segments to file.\cr } \bold{Methods inherited from AbstractCBS}:\cr adjustPloidyScale, all.equal, as.data.frame, clearCalls, drawChangePoints, drawKnownSegments, dropChangePoint, dropChangePoints, dropRegion, dropRegions, extractCNs, extractChromosome, extractChromosomes, extractRegions, extractSegments, extractWIG, getChangePoints, getChromosomeOffsets, getChromosomeRanges, getChromosomes, getLocusData, getLocusSignalNames, getMeanEstimators, getSampleName, getSegmentSizes, getSegmentTrackPrefixes, getSegments, mergeThreeSegments, mergeTwoSegments, nbrOfChangePoints, nbrOfChromosomes, nbrOfLoci, nbrOfSegments, normalizeTotalCNs, ploidy, ploidy<-, plotTracks, print, pruneByDP, pruneByHClust, renameChromosomes, report, resegment, resetSegments, sampleCNs, sampleName, sampleName<-, seqOfSegmentsByDP, setLocusData, setMeanEstimators, setPloidy, setSampleName, setSegments, shiftTCN, tileChromosomes, updateMeans, writeWIG \bold{Methods inherited from list}:\cr Ops,nonStructure,vector-method, Ops,structure,vector-method, Ops,vector,nonStructure-method, Ops,vector,structure-method, all.equal, as.data.frame, attachLocally, averageQuantile, callHooks, coerce,ANY,list-method, normalizeAverage, normalizeDifferencesToAverage, normalizeQuantileRank, normalizeQuantileSpline, plotDensity, relist, reset, type.convert, within } \section{Difference to DNAcopy object}{ A CBS object is similar to DNAcopy objects with the major difference that a CBS object holds only one sample, whereas a DNAcopy object can hold more than one sample. } \section{See also}{ The \code{\link{segmentByCBS}}() method returns an object of this class. } \author{Henrik Bengtsson} \keyword{classes} �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/nbrOfChangePoints.AbstractCBS.Rd����������������������������������������������������������0000644�0001762�0000144�00000002076�15000477031�017633� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{nbrOfChangePoints.AbstractCBS} \alias{nbrOfChangePoints.AbstractCBS} \alias{AbstractCBS.nbrOfChangePoints} \alias{nbrOfChangePoints,AbstractCBS-method} \title{Gets the number of change points} \description{ Gets the number of change points, which is defined as the number of segments minus the number of chromosomes. } \usage{ \method{nbrOfChangePoints}{AbstractCBS}(fit, ignoreGaps=FALSE, dropEmptySegments=TRUE, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns an \code{\link[base]{integer}}. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:nbrOfSegments.AbstractCBS]{*nbrOfSegments}()} \code{\link[PSCBS:nbrOfChromosomes.AbstractCBS]{*nbrOfChromosomes}()} For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/man/getLocusData.AbstractCBS.Rd���������������������������������������������������������������0000644�0001762�0000144�00000001761�15000477031�016641� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getLocusData.AbstractCBS} \alias{getLocusData.AbstractCBS} \alias{AbstractCBS.getLocusData} \alias{getLocusData,AbstractCBS-method} \alias{AbstractCBS.setLocusData} \alias{setLocusData.AbstractCBS} \alias{setLocusData,AbstractCBS-method} \alias{setLocusData.AbstractCBS} \title{Gets the locus-level data} \description{ Gets the locus-level data. } \usage{ \method{getLocusData}{AbstractCBS}(...) } \arguments{ \item{...}{Not used.} } \value{ Returns a JxL \code{\link[base]{data.frame}}, where J in the number of loci, and L is the number of locus-specific fields. } \author{Henrik Bengtsson} \seealso{ For more information see \code{\link{AbstractCBS}}. } \keyword{internal} \keyword{methods} ���������������PSCBS/man/getSampleName.AbstractCBS.Rd��������������������������������������������������������������0000644�0001762�0000144�00000001743�15000477031�017004� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{getSampleName.AbstractCBS} \alias{getSampleName.AbstractCBS} \alias{AbstractCBS.getSampleName} \alias{getSampleName,AbstractCBS-method} \alias{AbstractCBS.sampleName} \alias{sampleName.AbstractCBS} \alias{sampleName,AbstractCBS-method} \title{Gets the name of the sample segmented} \description{ Gets the name of the sample segmented. } \usage{ \method{getSampleName}{AbstractCBS}(fit, ...) } \arguments{ \item{...}{Not used.} } \value{ Returns a \code{\link[base]{character}} string. } \author{Henrik Bengtsson} \seealso{ \code{\link[PSCBS:setSampleName.AbstractCBS]{*setSampleName}()}. For more information see \code{\link{AbstractCBS}}.. } \keyword{internal} \keyword{methods} �����������������������������PSCBS/man/updateMeans.AbstractCBS.Rd����������������������������������������������������������������0000644�0001762�0000144�00000001711�15000477031�016523� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % AbstractCBS.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{updateMeans.AbstractCBS} \alias{updateMeans.AbstractCBS} \alias{AbstractCBS.updateMeans} \alias{updateMeans,AbstractCBS-method} \alias{updateMeans.CBS} \alias{updateMeans.NonPairedPSCBS} \alias{updateMeans.PairedPSCBS} \title{Updates the CN mean levels for each segment independently} \description{ Updates the CN mean levels for each segment independently as if they were one large segment. The locus-level data is not updated/modified. } \usage{ \method{updateMeans}{AbstractCBS}(...) } \arguments{ \item{...}{Arguments specific to the class.} } \value{ Returns an object of the same class. } \author{Henrik Bengtsson} \keyword{internal} \keyword{methods} �������������������������������������������������������PSCBS/man/callAllelicBalanceByDH.PairedPSCBS.Rd�����������������������������������������������������0000644�0001762�0000144�00000003344�15000477031�020343� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% % Do not modify this file since it was automatically generated from: % % PairedPSCBS.callAB.R % % by the Rdoc compiler part of the R.oo package. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \name{callAllelicBalanceByDH.PairedPSCBS} \alias{callAllelicBalanceByDH.PairedPSCBS} \alias{PairedPSCBS.callAllelicBalanceByDH} \alias{callAllelicBalanceByDH,PairedPSCBS-method} \title{Calls segments that are in allelic balance} \description{ Calls segments that are in allelic balance by thresholding on DH using a predetermined threshold. The variability of the DH mean levels is taken into account via a bootstrap estimator. } \usage{ \method{callAllelicBalanceByDH}{PairedPSCBS}(fit, delta=estimateDeltaAB(fit, flavor = "qq(DH)"), alpha=0.05, ..., verbose=FALSE) } \arguments{ \item{flavor}{A \code{\link[base]{character}} string specifying which type of call to use.} \item{delta}{(Tuning parameter) A non-negative \code{\link[base]{numeric}} threshold.} \item{alpha}{A \code{\link[base]{numeric}} in [0,1] specifying the upper and lower quantiles calculated by the bootstrap estimator.} \item{...}{Additional arguments passed to the bootstrap estimator \code{\link[PSCBS:bootstrapTCNandDHByRegion.PairedPSCBS]{*bootstrapTCNandDHByRegion}()}.} } \value{ Returns a \code{\link{PairedPSCBS}} object with allelic-balance calls. } \author{Henrik Bengtsson} \section{Algorithm}{ \itemize{ \item Foo \item Bar } } \seealso{ Instead of calling this method explicitly, it is recommended to use the \code{\link[PSCBS:callAllelicBalance.PairedPSCBS]{*callAllelicBalance}()} method. } \keyword{internal} \keyword{methods} ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������PSCBS/DESCRIPTION�����������������������������������������������������������������������������������0000644�0001762�0000144�00000003533�15000525222�012627� 0����������������������������������������������������������������������������������������������������ustar �ligges��������������������������users������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������Package: PSCBS Version: 0.68.0 Depends: R (>= 3.2.0) Imports: R.methodsS3 (>= 1.8.2), R.oo (>= 1.25.0), R.utils (>= 2.12.0), R.cache (>= 0.16.0), matrixStats (>= 0.62.0), aroma.light (>= 2.4.0), DNAcopy (>= 1.42.0), future (>= 1.28.0), parallel, graphics, grDevices, stats, utils Suggests: R.rsp (>= 0.45.0), R.devices (>= 2.17.1), ggplot2 (>= 3.2.1) SuggestsNote: BioC (>= 3.1) VignetteBuilder: R.rsp Title: Analysis of Parent-Specific DNA Copy Numbers Authors@R: c( person("Henrik", "Bengtsson", role=c("aut", "cre", "cph"), email="henrikb@braju.com"), person("Pierre", "Neuvial", role="aut"), person("Venkatraman E.", "Seshan", role="aut"), person("Adam B.", "Olshen", role="aut"), person("Paul T.", "Spellman", role="aut"), person("Richard A.", "Olshen", role="aut"), person("Frank E", "Harrell Jr", role="ctb", comment = "Weighted quantile estimator adopted from Hmisc::wtd.quantile()")) Description: Segmentation of allele-specific DNA copy number data and detection of regions with abnormal copy number within each parental chromosome. Both tumor-normal paired and tumor-only analyses are supported. License: GPL (>= 2) LazyLoad: TRUE ByteCompile: TRUE biocViews: aCGH, CopyNumberVariants, SNP, Microarray, OneChannel, TwoChannel, Genetics URL: https://github.com/HenrikBengtsson/PSCBS BugReports: https://github.com/HenrikBengtsson/PSCBS/issues NeedsCompilation: no Packaged: 2025-04-18 18:47:19 UTC; henrik Author: Henrik Bengtsson [aut, cre, cph], Pierre Neuvial [aut], Venkatraman E. Seshan [aut], Adam B. Olshen [aut], Paul T. Spellman [aut], Richard A. Olshen [aut], Frank E Harrell Jr [ctb] (Weighted quantile estimator adopted from Hmisc::wtd.quantile()) Maintainer: Henrik Bengtsson <henrikb@braju.com> Repository: CRAN Date/Publication: 2025-04-18 19:40:02 UTC ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������