seroincidence/0000755000176200001440000000000013305535606013072 5ustar liggesusersseroincidence/inst/0000755000176200001440000000000013305523607014045 5ustar liggesusersseroincidence/inst/CITATION0000644000176200001440000000113713273375665015221 0ustar liggesuserscitHeader("To cite package 'seroincidence' in publications use:") year <- sub(".*(2[[:digit:]]{3})-.*", "\\1", meta$Date, perl = TRUE) vers <- paste("R package version", meta$Version) url <- gsub("\n", "", meta$URL) citEntry(entry = "Manual", title = "seroincidence: Estimating Infection Rates from Serological Data", author = personList(as.person("Peter Teunis"), as.person("Jan van Eijkeren")), year = year, note = vers, url = url, textVersion = paste0("Peter Teunis and Jan van Eijkeren (", year, "). Estimating Infection Rates from Serological Data. ", vers, "."), ) seroincidence/inst/doc/0000755000176200001440000000000013305523607014612 5ustar liggesusersseroincidence/inst/doc/installation.Rmd0000644000176200001440000001404113305507007017753 0ustar liggesusers--- title: "Seroincidence package installation manual" author: "European Centre for Disease Prevention and Control (ECDC)" date: "`r Sys.Date()`" output: pdf_document: toc: yes header-includes: - \setkeys{Gin}{height=2.8in, keepaspectratio} \DeclareUnicodeCharacter{2010}{-} vignette: > %\VignetteIndexEntry{Seroincidence package installation manual} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} # Grab package version and date from DESCRIPTION file. pkgVersion <- packageDescription("seroincidence")$Version pkgDate <- packageDescription("seroincidence")$Date pkgBaseFileName <- paste("seroincidence", pkgVersion, sep = "_") pkgUrl <- gsub("\n", "", packageDescription("seroincidence")$URL) pkgPath <- "http://ecdc.europa.eu/en/data-tools/seroincidence-calculator-tool/Documents" library("knitr") ``` \newpage # 1. Introduction Package **seroincidence** is written in programming language R and end user must have access to a working installation of R engine. This document describes the most common setup with R installed locally on the user's computer. The screenshots refer to the classical R interface, but the package can also be opened in other Graphical User Interfaces fo R like e.g. [RStudio](http://www.rstudio.com/products/RStudio/). # 2. Installation steps R is a free software and can be downloaded from [http://cran.r-project.org/](http://cran.r-project.org/). Latest version as of writing this document is **R 3.5.0**. Once the appropriate, operating system dependent, version is downloaded, install it on your computer following the standard procedure applicable to the operating system. For Windows the file to be downloaded is the so-called *base* distribution: [http://cran.r-project.org/bin/windows/base/](http://cran.r-project.org/bin/windows/base/). ## 2.1. Installing R Start the R installer and follow the presented steps: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup1.png") ``` It is advised to have R installed in folder that does not contain spaces, therefore please adjust the destination location accordingly: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup2.png") ``` The **seroincidence** package is compatible with both the 32-bit and the 64-bit version of R. Choose the preferred platform (or both). If unsure install the 32-bit version only, however on compatible platforms the 64-bit version may provide better performance: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup3.png") ``` It is advised to select *Registry entries* in the next step for best experience: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup4.png") ``` R interpreter, when installed on Windows, can be invoked from the start menu folder named **R**. Start the preferred version of R (if both the 32-bit: *R i386* and the 64-bit: *x64* are installed). Graphical user interface for R interpreter will start in a new window: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui1.png") ``` ## 2.2. Installing *seroincidence* package Since this is a new installation of R, the **seroincidence** package must be installed before first use. The package can be installed either through a menu option in the graphical user interface (GUI) or with a command executed in the R console. Both options are presented: ### 2.2.1. Package installation from the graphical user interface Download the seroincidence calculator package from ECDC website: [`r pkgUrl`](`r pkgUrl`). Two versions of the package are made available: * binary package (seroincidence_[version].zip) - Microsoft Windows compatible * Source package (seroincidence_[version].tar.gz) - cross-platform compatible (MS Windows, Linux, MacOS) If your operating system is Windows then it is best to download the Windows binary package. Go to menu *Packages* and select command *Install package(s) from local files...*: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui2.png") ``` Select the package file and click "Open": ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui3.png") ``` Post-installation message should appear: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui4.png") ``` The package is now installed in R. ### 2.2.2. Package installation from R console Alternatively, installation of the package can also be performed by executing one of the following commands in the *R console*: ```{r, include=FALSE, tidy=FALSE} chunkTemplate <- "```{r, eval = FALSE} # OPTION A # Install Windows binary package \"seroincidence\" directly from internet ECDC website: install.packages( pkgs = \"{{pkgPath}}/ {{pkgBaseFileName}}.zip\", repos = NULL, type = \"win.binary\") # OPTION B # Install source package directly from internet CRAN repository: install.packages(\"seroincidence\") # OPTION C # Install Windows binary package from a local file: # install.packages(\"[PATH/TO/FILE/]seroincidence_[version].zip\", # repos = NULL, type = \"win.binary\") # For instance: install.packages(pkgs = \"C:/{{pkgBaseFileName}}.zip\", repos = NULL, type = \"win.binary\") # OPTION D # Install source package from a local file: install.packages(pkgs = \"C:/{{pkgBaseFileName}}.tar.gz\", repos = NULL, type = \"source\") ```" chunkSource <- knit_expand(text = chunkTemplate, pkgBaseFileName = pkgBaseFileName) ``` `r knit(text = chunkSource)` # 3. Post-installation Successful installation can be confirmed by loading the package into the workspace and exploring help files and manuals distributed with the package: ```{r, eval=FALSE} # Load package "seroincidence". library(seroincidence) # Show R help for the package. ?seroincidence # Show tutorial for the package. vignette(topic = "tutorial", package = "seroincidence") ``` Additionally, most package details can be found when executing the following commands: ```{r} # Show description. packageDescription("seroincidence") # Show citation. citation("seroincidence") ``` seroincidence/inst/doc/tutorial.pdf0000644000176200001440000032721013305535606017157 0ustar liggesusers%PDF-1.5 % 1 0 obj << /Type /ObjStm /Length 3915 /Filter /FlateDecode /N 64 /First 517 >> stream x[s6vܘ FLǎ;qe'q{LٺȢ+Qmz %ʔϝyƦb7L23ŌLeX̒X3ˢHD,a(,RLECD]1i?ew*_M%pw:Y>OKr&EdQV[ z(ǕvUp]mQRTdENZa"EBݯuơ[[C_c_-:EoX?l=I@gX,?&Hb@[p7bE}\IB)NbQ_p/[.Y| KSD Nypa'= t W§  c:p~Y6 "$\B@ mࣤ 9@AG yZ?3"֐e7B*IPyB 'B:A"'~Q @D: ,x-JAAɈX-y ~V e0ԝ!R^pݡ =[ޏπ |:-oULx:-?9lݏ8xob-^-V猼/)q sv~(\^!NCvNTb25dYgj{+f-tE\:)<3H%z!XlE/`(c؏GT'ʕ zqBU'IwnjBV5EW]YHw3c~'|ʧ0'/xƳE8Yv×|s-Ӕf|:<x+Bgǟץ9s~o=SE>^:A9Z$fDI{<Ve"^ B|ܒ_~9:m3jؔeS߭|$X=YLz 1xQMd!svS )x@HQQ]:\2k j^o]Lc%q4aJWъ) 뚘G51^GtwKZJJ7-G[B9$JG >Qmzwy2(]!Mُ:iȾPCOb Qc9X&|Xʺu1% ^]> Ћ#~82hj , z4xhCuhA"-7Vd;%njTU"#NNeByJQ>N=թNL;VkCأ;3|>/Wῥ9dM6,m]g{8OWX_ wu?pw9j-]Ѳ VRƥjQn]iCu#;\7;RPA(+&:ݩJϭv8=pwϽum<\?)j6^NiZ t%p?Ka}F`wLeod엏W{JjQGVKZ*,لFkc,yOzG/Era_>}WKM{(KYHAy8덒WƝ3΅s㎱yܷS9s.6vRpʻ,A]?-hFs"7]ц(~z,CCyɪ=tޞorà5[.Jvư۶eۦ;mbr^p䀭١p~{5uw&_ylSҿW6jh9a^MJ;T#Η=FB,͔&=.ts)LP|~&D MPdG/Er"9[tV iۨGtXopc xW+w.6{r'F]!aVyH(̝ctHH%vODHONقm_z N;+3+8};pqLEٸE@rs'ʏlʔJVh#ewܽɣb]5x>%(V 1*L}r6l-AS&v%p DΜNwdw:տ=FwV se26ڱwלls5tLX)i6]|qR 4WQ%ټiסeLWER}a җnPa1i>3ڶ|ybakJr[w7 ͝frvSįJrrZ3)/ ;B'4XƧB*B':C35{m,d9^˃eFpx|ŗtB1w^["GD$5*y'xl>,TY9=Mq--֫.B0̏{k} X\}ZE'-ߥO%jw(t.i0C/6/=2(LMgrգ2~V||:ucʳ-|o 8t+Nu_ѽendstream endobj 66 0 obj << /Subtype /XML /Type /Metadata /Length 1644 >> stream GPL Ghostscript 9.23 2018-06-05T17:08:56+02:00 2018-06-05T17:08:56+02:00 LaTeX with hyperref package Seroincidence package tutorialEuropean Centre for Disease Prevention and Control (ECDC) endstream endobj 67 0 obj << /Type /ObjStm /Length 2188 /Filter /FlateDecode /N 64 /First 537 >> stream xZ]o7}_ "86ڻi4%C=pH%GY u~Ee^2Ĝq+ Vļag22kF(FaY4 )m1Ύ` FT$&2Bd1mpNL[^bd:XŢd:"1CưQ53F-1k%y f,FP@HpxY- Ari@K1G1Mc蔷` O:)/Nve5>15'{q]]_K RZ#%%m^7s^XP:uMsy<ڛou:%{2Ch('B7u#hBhГnS7P#RV=:1D4ZsxMOD*b^k)g:1Ul{R<":cT1&ڎQǠQ,rUO`IsW2lM6cwXh ,U`uѡ%9aAv=53M "C<.([WI~/LþH;&oʘݿuXpSERpٴlV"׻j4}4Il V|+fZt_փʉ1o89;kΆUґx&E\_tMӦ [ٸyL݄l.EM5kRU6IմMX*k*_bO2T#*vO.ԥO[5#|O媭Z,.8jݯ6M;Zi- Q0%4Ԃj0<շ)[m&r#]ޗ>Bf3q9O[SMe~Y sXon%`1#Q1sQ)' ͂YWm7 Tjn'f:Y]Aԃxx:Athʃq岮>Fݎa/EFc&>~p䁑<<{0?mէ^]!ݡL w߆a*ca1c:`'=.|ϊwgAq-ǟ*q g |OxR]lX?3 >Vk-` |GxK}ϞM퓼VKo"΄ֻv"@sP+9|s>+.<1 8>4KodXgwwU};&/~t}.}g;|G,Fiӏ ʧo3Hdqĺd#Z !%[=qxT{ǧrRYhXID] :(9fMR{|I(U,E#=*cER1!+-yط: b-J>12YLVy|,b<o~7!F1o!v;xTq%2IuHRP K2{q*iyBt4XZn9[ܦCXMؓBL*opQɜTII7]8X`$M[(K#lP9$%"$a-Vmy:8Lt qMwN%0u+R1 L- -W`)e˳Jbp`endstream endobj 132 0 obj << /Filter /FlateDecode /Length 4866 >> stream x\w䶑u⃤o׻y}IV7hIӭ4[hD`HN&P(TުntU_?^}R_ZXxbڸ+溭mmJm77zNF+x46{g$k`m_ 6Vw0_nCӦ鶵iuJ~CYݪ^67n}U 5t~`Ǿ+x70=Gt=vR۾pWwܡSaG 4'^WeZ :oֵ~E;U~Oo7aDN1䴆0yV?Σ֦="B#a:>~t9+٧qO#g ~JZU45=mbhSXnӧgcy/.~tQlyytT?D]ƻM`[U&7G// %fuӴqV3 Uc7aQ-'06F&2>"R9ZH (IlW%3rA~J ?o҅䁘vf7~uEt^V+fmEBut Äb,\_Ӂ*;47` cGG9jN3g@v60i/Nkdfc<B~|z-m&e>w@Cq}{ܴ֑ μNȋ{<ٓE^ FiZiKGe$p{{XxZ"['j_' ZeEAN~}1W:h( YsrD`1ς |m-Cp$ԍ٤yh?0!'>QKUihIc@Acӡȡ"̖Fj* Bohu.3^NHQt`;&ֺAy(m睳[pLkv +}!:g گ]fOT.c؂DhM~O'Me%PªcPS <ҧ< tF58W~aQ>,06acnMcQhő|l?eȍi}o(#7 (_G0|g{5hgZJR_gZ<=hz<t<'g,Yλ"8&vS|Pgyp]27Lќ fq-BBe, تj N B+(M&_Оvh؟vtNW]w&qN .rmnp(N;E6:{ZD_ Y2KQ㐹.0E\T:_ @!=wRg(a`A| (up^IJӽiob?V$@źyYPmׇ3u%jSUHRT:(嘥j)GX=M_bdk5Gְ Z1zøu^$4>dcDR)ZFÄ-ж 1k)a9/lwȒEy,7iv~X4!ڕ̏Q]+IiΏ3 &]C [NkX! 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R Package - seroincidence

European Centre for Disease Prevention and Control (ECDC)

R package seroincidence allows translation of antibody levels measured in a (cross-sectional) population sample into an estimate of the frequency with which seroconversions (infections) occur in the sampled population.

Item Data
Version 2.0.0
Published 2018-06-05
Authors Peter Teunis,
p.teunis@emory.edu,
Author of the method and original code.

Jan van Eijkeren,
Author of the method and original code.

Daniel Lewandowski,
daniel@nextpagesoft.net,
Creator of the R package.

Chantal Quinten,
seroincidence@ecdc.europa.eu,
Project manager and the package maintainer.
Maintainer Chantal Quinten seroincidence@ecdc.europa.eu
License GPL-3
Installation manual installation.pdf
Tutorial tutorial.pdf
Appendix methodology.pdf
ECDC web site https://ecdc.europa.eu/en/publications-data/seroincidence-calculator-tool
seroincidence/inst/doc/methodology.Rmd0000644000176200001440000004225513305523173017616 0ustar liggesusers--- title: "Seroincidence package methodology" author: "European Centre for Disease Prevention and Control (ECDC)" date: '`r Sys.Date()`' output: pdf_document: toc: yes header-includes: - \usepackage{subfigure} \DeclareUnicodeCharacter{2010}{-} references: - id: teunis_etal12_biomarker DOI: 10.1002/sim.5322 author: - family: Teunis given: P. F. M. - family: van Eijkeren given: J. C. - family: Ang given: C. W. - family: van Duynhoven given: Y. T. - family: Simonsen given: J. B. - family: Strid given: M. A. - family: van Pelt given: W. container-title: Statistics in Medicine issue: 20 issued: month: 9 year: 2012 page: 2240-2248 title: 'Biomarker dynamics: estimating infection rates from serological data' type: article-journal volume: 31 - id: degraaf_etal14wh author: - family: de Graaf given: W. F. - family: Kretzschmar given: M. E. E. - family: Teunis given: P. F. M. - family: Diekmann given: O. container-title: Epidemics DOI: 10.1016/j.epidem.2014.08.002 issued: month: 12 year: 2014 page: 1-7 title: 'A two-phase within-host model for immune response and its application to serological profiles of pertussis' type: article-journal volume: 9 - id: teunis_etal16withinhost author: - family: Teunis given: P. F. M. - family: van Eijkeren given: J. C. - family: de Graaf given: W. F. - family: Bonačić Marinović given: A. - family: Kretzschmar given: M. E. E. container-title: Epidemics DOI: 10.1016/j.epidem.2016.04.001 issued: month: 9 year: 2016 page: 33-39 title: 'Linking the seroresponse to infection to within-host heterogeneity in antibody production' type: article-journal volume: 16 - id: satten_etal04 author: - family: Satten given: G. A. - family: Kong given: F. - family: Wright given: D. J. - family: Glynn given: S. A. - family: Schreiber given: G. B. container-title: Biostatistics DOI: 10.1093/biostatistics/5.1.145 issued: month: 1 year: 2004 page: 145-151 title: 'How special is a ‘special’ interval: modeling departure from length‐biased sampling in renewal processes' type: article-journal volume: 5 issue: 1 - id: zelen04 author: - family: Zelen given: M. container-title: Lifetime Data Analysis issued: month: 12 year: 2004 page: 325-334 title: 'Forward and backward recurrence times and length biased sampling: age specific models' type: article-journal volume: 10 issue: 4 - id: degreeff_etal12 author: - family: de Greeff given: S. C. - family: Teunis given: P. F. M. - family: de Melker given: H. E. - family: Mooi given: F. R. - family: Notermans given: D. W. - family: Elvers given: B. - family: Schellekens given: J. F. P. container-title: Clinical and Vaccine Immunology DOI: 10.1128/CVI.00229-12 issued: month: 9 year: 2012 page: 1452-1456 title: 'Two-Component Cluster Analysis of a Large Serodiagnostic Database for Specificity of Increases of IgG Antibodies against Pertussis Toxin in Paired Serum Samples and of Absolute Values in Single Serum Samples' type: article-journal volume: 19 issue: 9 fontsize: 11pt vignette: > %\VignetteIndexEntry{Seroincidence package methodology} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- \newpage # Introduction The revised seroincidence calculator package provides three refinements to the method for calculating seroincidence published earlier [@teunis_etal12_biomarker] and implemented in R package **seroincidence**, versions 1.x: (1) inclusion of infection episode with rising antibody levels, (2) non--exponential decay of serum antibodies after infection, and (3) age--dependent correction for subjects who have never seroconverted. It is important to note that, although the implemented methods use a specific parametric model, as proposed in [@degraaf_etal14wh] and augmented in [@teunis_etal16withinhost], the methods used to calculate the likelihood function allow seroresponses of arbitrary shape. # 1. A simple model for the seroresponse The current version of the seroincidence package uses the model of [@teunis_etal16withinhost] for the shape of the seroresponse: $$ \begin{array}{l@{\qquad}l} \text{Infection/colonization episode} & \text{Waning immunity episode}\\ b^{\prime}(t) = \mu_{0}b(t) - cy(t) & b(t) = 0 \\ y^{\prime}(t) = \mu y(t) & y^{\prime}(t) = -\nu y(t)^r \\ \end{array} $$ With baseline antibody concentration $y(0) = y_{0}$ and initial pathogen concentration $b(0) = b_{0}$. The serum antibody response $y(t)$ can be written as $$ y(t) = y_{+}(t) + y_{-}(t) $$ where \begin{align*} y_{+}(t) & = y_{0}\text{e}^{\mu t}[0\le t 1$, log concentrations decrease rapidly after infection has terminated, but decay then slows down and low antibody concentrations are maintained for a long period. When $r$ approaches 1, exponential decay is restored. # 2. Backward recurrence time Considering the (fundamental) uniform distribution $u_{f}$ of sampling within a given interval, the interval length distribution $p(\Delta t)$ and the distribution of (cross--sectionally) sampled interval length [@teunis_etal12_biomarker] $$ q(\Delta t) = \frac{p(\Delta t)\cdot\Delta t}{\overline{\Delta t_{p}}} $$ the joint distribution of backward recurrence time and cross--sectional interval length is the product $u_{f}\cdot q$ because these probabilities are independent. The distribution of backward recurrence time is the marginal distribution \begin{align*} u(\tau) & = \int_{\Delta t=0}^{\infty} u_{f}(\tau;\Delta t)\cdot q(\Delta t)\text{d}\Delta t\\ & = \int_{0}^{\infty}\frac{[0\le\tau\le\Delta t]}{\Delta t}\cdot \frac{p(\Delta t)\cdot \Delta t}{\overline{\Delta t_{p}}}\text{d}\Delta t\\ & = \frac{1}{\overline{\Delta t_{p}}}\int_{\tau}^{\infty}p(\Delta t)\text{d}\Delta t \end{align*} # 3. Incidence of seroconversions To calculate the incidence of seroconversions, as in [@teunis_etal12_biomarker], the distribution $p(\Delta t)$ of intervals $\Delta t$ between seroconversions, is important. Assuming any subject is sampled completely at random during their intervals between seroconversions, and accounting for interval length bias [@satten_etal04; @zelen04], the distribution of backward recurrence times $\tau$ can be written as [@teunis_etal12_biomarker] $$ u(\tau) = \frac{1}{\overline{\Delta t}} \int_{\tau=0}^{\infty}p(\Delta t)\text{d}\Delta t = \frac{1-P(\Delta t)}{\overline{\Delta t}} $$ where $\overline{\Delta t}$ is the $p$--distribution expected value of $\Delta t$. This density is employed to estimate seroconversion rates. The antibody concentration $y$ is the observable quantity, and we need to express the probability (density) of observed $y$ in terms of the density of backward recurrence time. 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F. - family: Kretzschmar given: M. E. E. - family: Teunis given: P. F. M. - family: Diekmann given: O. container-title: Epidemics DOI: 10.1016/j.epidem.2014.08.002 issued: month: 12 year: 2014 page: 1-7 title: 'A two-phase within-host model for immune response and its application to serological profiles of pertussis' type: article-journal volume: 9 - id: 2 author: - family: Simonsen given: J. - family: Mølbak given: K. - family: Falkenhorst given: G. - family: Krogfelt given: K. A. - family: Linneberg given: A. - family: Teunis given: P. F. container-title: Statistics in Medicine DOI: 10.1002/sim.3592 issue: 14 issued: month: 6 year: 2009 page: 1882-1895 title: 'Estimation of incidences of infectious diseases based on antibody measurements' type: article-journal volume: 28 - id: 3 author: - family: Teunis given: P. F. - family: van Eijkeren given: J. C. - family: Ang given: C. W. - family: van Duynhoven given: Y. T. - family: Simonsen given: J. B. - family: Strid given: M. A. - family: van Pelt given: W. container-title: Statistics in Medicine DOI: 10.1002/sim.5322 issue: 208 issued: month: 9 year: 2012 page: 2240-2248 title: 'Biomarker dynamics: estimating infection rates from serological data' type: article-journal volume: 31 - id: 4 author: - family: Teunis given: P. F. - family: van Eijkeren given: J. C. - family: de Graaf given: W. F. - family: Bonačić Marinović given: A. - family: Kretzschmar given: M. E. E. container-title: Epidemics DOI: 10.1016/j.epidem.2016.04.001 issued: month: 9 year: 2016 page: 33-39 title: 'Linking the seroresponse to infection to within-host heterogeneity in antibody production' type: article-journal volume: 16 - id: 5 author: - family: Strid given: M. A. - family: Engberg given: J. - family: Larsen, given: L. B. - family: Begtrup given: K - family: Mølbak given: K - family: Krogfelt given: K. A. title: 'Antibody responses to Campylobacter infections determined by an enzyme--linked immunosorbent assay: 2-year follow-up study of 210 patients' container-title: Clinical and Vaccine Immunology issue: 8 volume: 2 page: 314-319 issued: year: 2001 month: 3 DOI: 10.1128/CDLI.8.2.314-319.2001 fontsize: 11pt vignette: > %\VignetteIndexEntry{Seroincidence package tutorial} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} pkgUrl <- gsub("\n", "", packageDescription("seroincidence")$URL) ``` \newpage # 1. Introduction Antibody levels measured in a (cross–sectional) population sample can be translated into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. In simple terms: the presence of many high antibody concentrations indicates that many subjects likely experienced infection recently, while mostly low concentrations indicate a low frequency of infections in the sampled population. More information about ELISA methods can be found on [ECDC web site](`r pkgUrl`). In order to thus interpret the measured cross-sectional antibody concentrations, characteristics of the time course of the serum antibody response must be known. For any antibody detected in the cross–sectional sample, a quantitative description of its dynamics following infection (seroconversion to an elevated concentration, followed by a gradual decrease) must be available. In published studies, this information on the time course of the serum antibody response has been obtained from follow–up data in subjects who had a symptomatic episode following infection. The onset of symptoms thus provided a proxy for the time that infection occurred. Care must be taken that longitudinal and cross–sectional measurements of antibody concentrations are calibrated on the same scale (or, preferably, expressed in identical units). The time course of the serum antibody response to infection is assumed generic: anyone infected by the same pathogen is expected to produce a response similar to those seen in the symptomatic cohort used for the follow–up study. Thus, the strategy is to set up a longitudinal model from a follow–up study once, and use the thus obtained information to analyze many different cross–sectional data sets. Note that it must be assumed that such variation in the time course of antibody concentrations among individuals as observed in the longitudinal cohort is the same as in the population where the cross-sectional sample was taken, where this variation cannot be observed. Analysis of longitudinal data and estimation of the required parameters is separated from the estimation of seroincidences, because (1) there are few longitudinal data sets available and they are difficult (and expensive) to obtain, (2) such longitudinal models may be considered *generic*, presumably describing a physiological phenomenon that is similiar in any infected individual, and (3) setting up and running the longitudinal model requires additional skills, not necessary for use of the sero–incidence calculator script # 2. The seroincidence estimator Package **seroincidence** was designed to calculate incidence of seroconversion, by using the longitudinal seroresponse characteristics. The distribution of serum antibody concentrations in a cross–sectional population sample is calculated, as a function of the (longitudinal) seroresponse and the frequency of seroconversion (or seroincidence). Given the seroresponse, this (marginal) distribution of antibody concentrations can be fitted to the cross-sectional data, by adjusting the seroconversion frequency, thus providing a means to estimate the seroconversion frequency. ## 2.1 Time course of serum antibodies The seroresponse, the time course of serum antibodies following seroconversion (infection) is described by means of a set of parameters describing it. These parameters may include: a) baseline antibody concentration, b) time to reach peak antibody concentration, c) magnitude of the peak concentration, and d) antibody decay parameters describing the time course (shape and rate) of antibody decay. A model description that is used for the serocalculator is described in [@2; @3]. An alternative model, simplified but with improved interpretation of the underlying biological mechanisms, is given in [@1] and further improved in [@4]. The current model assumes that upon exposure to an initial inoculum, pathogen concentrations increase exponentially. Presence of pathogens (antigen presented to the immune system) signals an increase in antibody production, resulting in exponentially increasing serum antibody concentrations. Increased activity of the immune system, as signalled by circulating antibodies, causes inactivation or die–off of pathogens, with a rate proportional to the serum antibody concentration. Ultimately, when all pathogens are removed, infection is over and the promotion of antibody production stops. Then the decay phase starts, and serum antibody concentrations decrease. Antibody decay in the serum compartment may start fast and slow down later, resulting in non–exponential decay. In [@4] this is modelled using a shape parameter, allowing gradual adjustment between exponential (log–linear) and strongly non–exponential decay. ## 2.2 Heterogenity The five parameters describing the seroresponse (in round brackets names of corresponding parameters used in the package, see [section 3.2.2](#longParams) for details): baseline antibody concentration (`y0` and `yb`), time to peak (`t1`), peak antibody concentration (`y1`), decay rate (`alpha`) and shape factor of the decay curve (`r`) are not fixed numbers. In a population of subjects, individuals each have their own seroresponse, different from those of other subjects. Therefore, these parameters are provided as a (joint) distribution, describing their variation among individuals in the sampled population. Of course, such a distribution depends on the pathogen, the detected antibody, and even the detection assay. Estimates for these seroresponse parameters may be obtained by fitting the model to longitudinal data. Typically, such data are collected in patients with confirmed infection, where the time of infection is detected by appearance of symptoms. Ideally, blood samples are taken at several times post infection, up to a period long enough to reliably estimate the shape of the serum antibody decay curve. A Bayesian hierarchical framework allows for individual variation in seroresponses, so that one obtains the (posterior) joint distribution of the parameters as a (Markov chain) Monte Carlo sample, of all relevant parameters [@4]. Note that, due to the limited number of iterations in the Monte Carlo sample, the generated incidence estimates will show minor variations: if the same calculation is run twice, the outcomes may differ slightly. If this variation should be smaller, the size of the Monte Carlo sample may be increased. This however will slow down the calculations. ## 2.3 Incidence estimation The longitudinal seroresponses are considered generic: they represent the time course of (specific) human serum antibodies against a (specific) pathogen. Therefore, with any cross–sectional sample of the same antibodies in a human population, an incidence estimate can be calculated. Given the longitudinal response characteristics, **seroincidence** R package provide a rapid and computationally simple method for calculating seroconversion rates, as published in [@3]. The methods on which the seroincidence calculator is based were developed with publicly funded research. All procedures have been published and are open to the general public, including the core script on which the seroincidence calculator is based. To make the functionalities provided as broadly available as possible, R was chosen as the computing platform, because it is free and open source, and runs on any modern computer operating system. ## 2.4 Model variants The package contains longitudinal models for seroincidence calculations. Four model variants are possible, depending on whether seroconversion is instantaneous ($t_{1} = 0$) or not ($t_{1} > 0$), and whether decay is exponential ($r = 1$) or proceeds as a power function ($r > 1$). Power function decay allows for rapid inital decay followed by a sustained period of very slow decay [@4]. Available model variants are described in Table 1. \begin{table}[!h] \centering \caption{Model variants} \vspace{0.3cm} \begin{footnotesize} \begin{tabular}{ccc} & Time to & Decay\\ Model & Seroconversion ($t_{1}$) & parameter ($r$)\\ 1 & 0 & 1\\ 2 & 0 & $> 1$\\ 3 & $> 0$ & 1\\ 4 & $> 0$ & $> 1$\\ \end{tabular} \begin{tabular}{lllcccc} & & & \multicolumn{4}{c}{Model}\\ Pathogen & Antibody & Units & 1 & 2 & 3 & 4\\ \hline {\em Campylobacter jejuni} & IgG & ELISA (Delft) & * & & * & * \\ & IgM & ELISA (Delft) & * & & * & * \\ & IgA & ELISA (Delft) & * & & * & * \\ & IgG & ELISA (SSI) & * & * & & * \\ & IgM & ELISA (SSI) & * & * & & * \\ & IgA & ELISA (SSI) & * & * & & * \\ \hline {\em Salmonella} & IgG & mixed ELISA (SSI) & * & * & & * \\ & IgM & mixed ELISA (SSI) & * & * & & * \\ & IgA & mixed ELISA (SSI) & * & * & & * \\ \hline {\em Bordetella pertussis} & IgG-PT & IU & * & * & * & * \\ \hline \end{tabular} \end{footnotesize} \end{table} # 3. How to use *seroincidence* package This section provides step-by-step directions on the usage of the *seroincidence* package. ## 3.1. Loading the package Functionality of the *seroincidence* package is made available to the end user only once the library is loaded into the current workspace. Assuming the package is installed already (covered in [installation.pdf](installation.pdf)) loading is achieved by running the following command in the R console (bear in mind that the text after character `#` is only a comment): ```{r} # Load package "seroincidence" library(seroincidence) ``` At this moment all functions required to run the seroincidence calculation are made available. It can be checked by running: ```{r, eval=FALSE} # List all objects (functions and data) exposed by package "seroincidence". ls("package:seroincidence") ``` Here is the resulting output: ```{r, echo=FALSE} ls("package:seroincidence") ``` We briefly describe the most important objects and functions: a) `[DISEASE]Params[MODEL_TYPE]`: Monte Carlo sample of longitudinal response parameters per antibody for various diseases: Campylobacter, Pertussis, Salmonella. Object class: `list`. b) `[DISEASE]Sim[Low|Medium|High]Data`: Example simulated antibody levels data measured in a cross-sectional population for three values of lambda (incidence): 0.036 ("Low"), 0.21 ("Medium") and 1.15 ("High") (1/yr). Object class: `data.frame`. c) `getAdditionalData`: Utility function for downloading additional longitudinal response parameters from an online repository. Files available for download are `coxiellaIFAParams4.zip` and `yersiniaSSIParams4.zip`. Object class: `function`. d) `estimateSeroincidence`: Main function of the package. Estimates seroincidence based on supplied cross-section antibody levels data and longitudinal response parameters. Object class: `function`. ## 3.2. Specifying input data There are two sets of inputs to the serology calculator that must always be specified: a) Simulated antibody levels measured in cross-sectional population sample (see `campylobacterSimLowData`, `campylobacterSimMediumData`, etc. above). b) Longitudinal response characteristic as set of parameters `(y1, alpha, yb, r, y0, mu1, t1)` (see `campylobacterDelftParams1`, `campylobacterSSIParams2`, etc. above). We start with loading antibody levels measured in cross-sectional population sample. ### 3.2.1. Specifying cross-sectional antibody levels data The user has a few options of providing this data to the calculator: **i) Using supplied sample data** Data set `campylobacterSimMediumData` provides an example of a cross-sectional antibody levels data for Campylobacter. It is loaded into the workspace as soon as the package is loaded, therefore it can be referenced right away. Here is a small exempt from this data set: ```{r} # Show three first rows of "campylobacterSimMediumData" data.frame. head(campylobacterSimMediumData, 3) ``` Let us create the serology data `serologyData` based on this data set: ```{r} # Assign data.frame "campylobacterDelftData" to object named "serologyData". serologyData <- with(campylobacterSimMediumData, data.frame( Age = Age, IgG = IgG, IgM = IgM, IgA = IgA, AgeCat = cut(Age, 15, labels = FALSE))) # Print a few first observations. head(serologyData) ``` You can view the data also in a tabular form: ```{r, eval=FALSE} View(serologyData) ``` We shall pass this object later to the calculator. Object `serologyData` must contain at least one column named `IgG`, `IgM`, or `IgA`. Additionally, column `Age` is used in the calculations if it is present. Otherwise, it is created on-the-fly and initialized to `NA` (not available). Column `Age`, if supplied, is assumed to represent age in days. Please, note that the cross-sectional data set can include extra columns allowing performing the seroincidence calculations stratified per factors available in those data. In the example above column `AgeCat` can be used as a *stratum* variable. This particular variable is created by mapping the age in days (column `Age`) into 15 categories, category 1 grouping the youngest subjects and category 15 grouping the oldest subjects. **ii) Loading from external files** The user can load her/his own data into an R session. Details on loading specific file types can be found in online R manual on [R Data Import/Export](http://cran.r-project.org/doc/manuals/r-release/R-data.html). It is important that the input data is in a tabular form with each column containing levels measured for a single antibody type. Column name should indicate name of the measured antibody. For instance, a comma separated file with the following content: ``` IgG, IgM, IgA 5.337300, 0.4414653, 0.3002395 3.534118, 0.3888226, 0.3543486 2.144549, 0.3320178, 0.3884205 2.957854, 0.4967764, 0.3472340 ``` is a valid cross-sectional data set. Suppose this file is named `c:\cross-sectional-data.csv`. Then it can be loaded into R like this: ```{r, eval=FALSE} # Read content of file "C:\cross-sectional-data.csv" into object named # "serologyData". serologyData <- read.csv(file = "C:\\cross-sectional-data.csv") ``` ### 3.2.2. Specifying longitudinal response parameters {#longParams} The longitudinal response parameters set consists of the following items: - `y1`: antibody peak level (ELISA units) - `alpha`: antibody decay rate (1/days for the current longitudinal parameter sets) - `yb`: baseline antibody level at $t$ approaching infinity ($y(t->inf)$) - `r`: shape factor of antibody decay - `y0`: baseline antibody level at $t=0$ ($y(t=0)$) - `mu1`: initial antibody growth rate - `t1`: duration of infection Please, refer to vignette [methodology.pdf](methodology.pdf) for more details on the underlying methodology. End user has three options for loading the response parameters into R session: **i) Using supplied data** There are a few longitudinal response parameter data sets provided by the package including Monte-Carlo sample of longitudinal response parameters, like `campylobacterDelftParams4`. This particular object is a list containing three data.frame objects named `IgG`, `IgM` and `IgA`. Let's have a pick into each of these two data sets separately (notice character `$` indicating a sub-object of the parent object): ```{r} # Show first rows of data.frame "IgG" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgG) # Show first rows of data.frame "IgM" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgM) # Show first rows of data.frame "IgA" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgA) ``` Let us assign object `campylobacterDelftParams4` to variable `responseParams`: ```{r} responseParams <- campylobacterDelftParams4 ``` **ii) Loading from local external files** Alternatively, this data can be loaded from an external file. Bear in mind, that most likely your data is organized into three files, separately for antibody `IgG`, `IgM` and `IgA`. Assuming that the data is saved into csv files named `IgG.csv`, `IgM.csv` and `IgA.csv` the end user would run the following code in order to create a valid input to the calculator: ```{r, eval=FALSE} IgGData <- read.csv(file = "IgG.csv") IgMData <- read.csv(file = "IgM.csv") IgAData <- read.csv(file = "IgA.csv") # Create a list named "responseData" containing objects named "IgG", "IgM" and # "IgA". responseParams <- list(IgG = IgGData, IgM = IgMData, IgA = IgAData) ``` Note that object `responseParams` is a list with three dataframes named `IgG`, `IgM` and `IgA` as required. **iii) Loading from an external repository** Finally, response parameters can be obtained from an online repository set up for this package. The repository is hosted on ECDC servers. At the time of publishing this package two files are available: a) `coxiellaIFAParams4.zip`: longitudinal response parameters per antibody for Coxiella. b) `yersiniaSSIParams4.zip`: longitudinal response parameters per antibody for Yersinia. Simply use the supplied utility function `getAdditionalData` to download this data: ```{r, eval=FALSE} responseParams <- getAdditionalData("coxiellaIFAParams4.zip") ``` Internet connection is needed for this function to work. ## 3.3. Estimating seroincidence Main calculation function provided by package *seroincidence* is called `estimateSeroincidence`. It takes several arguments: - `data`: A data frame with the cross-sectional data (see variable `serologyData` above). This may be the whole data set loaded from file, but can also be a subset, e.g. `data = serologyData[1, ]` to use only the first row. In this tutorial this is the data loaded into variable `serologyData`. It is a required input. - `antibodies`: A list of antibodies to be used. This can be a triplet (`antibodies = c("IgG", "IgM", "IgA")`) or any single antibody (`antibodies = c("IgG")`) or a combination of any two antibodies. It is a required input. - `strata`: A list of categories to stratify data. The column `AgeCat` in the example data set can be used as an example. If `strata = ""` (default), then the whole data set is treated as a single stratum; if each sample is assigned a unique identifier (e.g. `strata = "AgeCat"`) there are as many strata as there are samples and an incidence estimate is calculated for each sample. If not specified, then `strata` is initialized to `""`. - `params`: A list with the longitudinal parameters for all antibodies specified. In this tutorial this is the data loaded into variable `responseParams`. It is a required input. - `censorLimits`: A list of cutoff levels, one for each antibody used. These are antibody levels below which observations should be treated as censored. It is a required input. - `par0`: List of parameters for the (lognormal) distribution of antibody concentrations for true seronegatives (i.e. those who never seroconverted), by named antibody type (corresponding to `data`). - `start` A starting value for `log(lambda)`. Value of -6 corresponds roughly to 1 day (`log(1/365.25)`), value of -4 corresponds roughly to 1 week (`log(7/365.25)`). Users are adivised to experiment with this value to confirm that convergence to the same estimate is obtained. Default is -6. - `numCores` Number of processor cores to use for calculations when computing by `strata`. If set to more than 1 and R package `parallel` is available (installed by default), then the computations by stratum are executed in parallel. Default is 1, ie. no execution in parallel. Here is an example of the *Campylobacter* seroincidence calculation for three antibodies measured, stratified per `AgeCat`, and with measurements below `0.1` removed: ```{r, eval=FALSE} # Prepare input data. serologyData <- with(campylobacterSimMediumData, data.frame( Age = rep(NA, nrow(campylobacterSimMediumData)), IgG = IgG, IgM = IgM, IgA = IgA, AgeCat = cut(Age, 15, labels = FALSE))) responseParams <- campylobacterDelftParams4 cutOffs <- list(IgG = 0.1, IgM = 0.1, IgA = 0.1) # Baseline distributions: the distributions of antibody concentrations in # subjects who have never seroconverted. baseLine <- list(IgG = c(log(0.05), 1), IgM = c(log(0.005), 1), IgA = c(log(0.005), 1)) # Assign output of function "estimateSeroincidence" to object named # "seroincidenceData". Use all available processor cores. seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG", "IgM", "IgA"), strata = "AgeCat", params = responseParams, censorLimits = cutOffs, par0 = baseLine, start = -4, numCores = parallel::detectCores()) # Show content of the output variable... print(seroincidenceData) # ...or simply type in the console: 'seroincidenceData' (without "'") and # press ENTER. ``` The following text should be printed. ## Seroincidence object estimated given the following setup: ## a) Antibodies : IgG, IgM, IgA ## b) Strata : AgeCat ## c) Censor limits: IgG = 0.1, IgM = 0.1, IgA = 0.1 ## ## This object is a list containing the following items: ## Fits - List of outputs of "optim" function per stratum. ## Antibodies - Input parameter antibodies of function "estimateSeroincidence". ## Strata - Input parameter strata of function "estimateSeroincidence". ## CensorLimits - Input parameter censorLimits of function "estimateSeroincidence". ## ## Call summary function to obtain output results. The most important output is subobject `Fits` containing raw results on the output incidence. Translation of these raw results is provided by a custom function `summary` explained in the following section. The cutoff argument is based on censoring of the observed serum antibody measurements [@5]. Cut-off levels must always be specified when calling function `estimateSeroincidence` (argument `censorLimits`). Value `0` should be set for antibody measurements where no censoring is needed, for instance ```{r, eval=FALSE} censorLimits <- list(IgG = 0, IgM = 0, IgA = 0) ``` Using different censoring levels will produce different results. Choosing higher cut-off causes the estimates of lambda to decrease. Results should be published together with the chosen cut-off values. The cut-off level of `0.1` set in the example above is a typical value, but users should set it to value reflecting the censoring level in the data. ## 3.4. Getting a summary of seroincidence Output of the calculator should be passed in to function `summary` calculating output results: ```{r, eval=FALSE} summary(seroincidenceData) ``` ## Seroincidence estimated given the following setup: ## a) Antibodies : IgG, IgM, IgA ## b) Strata : AgeCat ## c) Censor limits: IgG = 0.1, IgM = 0.1, IgA = 0.1 ## d) Quantiles : 0.025, 0.975 ## ## Seroincidence estimates: ## Lambda.est Lambda.lwr Lambda.upr Deviance Convergence Stratum ## 1 0.09721890 0.06397004 0.14774909 105.29815 0 1 ## 2 0.05497303 0.03573489 0.08456817 181.90627 0 2 ## 3 0.04456096 0.02845903 0.06977327 199.99357 0 3 ## 4 0.02944038 0.01715302 0.05052964 141.32558 0 4 ## 5 0.02569781 0.01436524 0.04597053 123.33213 0 5 ## 6 0.02565297 0.01587275 0.04145941 187.41060 0 6 ## 7 0.03458616 0.02012722 0.05943207 128.84486 0 7 ## 8 0.02776873 0.02640621 0.02920154 133.57166 52 8 ## 9 0.04016261 0.02133209 0.07561541 94.99389 0 9 ## 10 0.01996477 0.01898409 0.02099612 104.30992 52 10 ## 11 0.03356017 0.01917771 0.05872886 141.20168 0 11 ## 12 0.05287648 0.03263923 0.08566140 181.68655 0 12 ## 13 0.05081097 0.02946963 0.08760729 123.66670 52 13 ## 14 0.04813104 0.02945312 0.07865371 186.92218 0 14 ## 15 0.03421042 0.02210895 0.05293569 215.78684 0 15 The `summary` function returns a list of objects as well. It contains sub-objects `Antibodies`, `Strata`, `CensorLimits`, `Quantiles` and `Results`. The most important sub-object of the output of the `summary` functions is `Results`, containing estimates of `Lambda` (annual incidence) together with their lower and upper bounds (`Lambda.lwr` and `Lambda.upr`, respectively). The default lower bound is 2.5% and the upper bound is 97.5% of the distribution of `Lambda`. These values can be changed (see [Other examples](#other-examples)). Optionally, the summary function returns also `Deviance` (negative log likelihood at the estimated `Lambda`) and `Convergence` (indicator returned by function `stats::optim`; value of 0 indicates convergence). It may be beneficial to assign output of this function to a variable for further analysis: ```{r, eval=FALSE} # Compute seroincidence summary and assign to object "seroincidenceSummary". seroincidenceSummary <- summary(seroincidenceData) # Show the results. seroincidenceSummary$Results ``` ## Lambda.est Lambda.lwr Lambda.upr Deviance Convergence Stratum ## 1 0.09721890 0.06397004 0.14774909 105.29815 0 1 ## 2 0.05497303 0.03573489 0.08456817 181.90627 0 2 ## 3 0.04456096 0.02845903 0.06977327 199.99357 0 3 ## 4 0.02944038 0.01715302 0.05052964 141.32558 0 4 ## 5 0.02569781 0.01436524 0.04597053 123.33213 0 5 ## 6 0.02565297 0.01587275 0.04145941 187.41060 0 6 ## 7 0.03458616 0.02012722 0.05943207 128.84486 0 7 ## 8 0.02776873 0.02640621 0.02920154 133.57166 52 8 ## 9 0.04016261 0.02133209 0.07561541 94.99389 0 9 ## 10 0.01996477 0.01898409 0.02099612 104.30992 52 10 ## 11 0.03356017 0.01917771 0.05872886 141.20168 0 11 ## 12 0.05287648 0.03263923 0.08566140 181.68655 0 12 ## 13 0.05081097 0.02946963 0.08760729 123.66670 52 13 ## 14 0.04813104 0.02945312 0.07865371 186.92218 0 14 ## 15 0.03421042 0.02210895 0.05293569 215.78684 0 15 As one may note it is a dataframe with six columns that can be later post-processed with custom calculations. # 4. Other examples The following examples show the standard procedure for estimating seroincidence. ```{r, eval=FALSE} # 1. Define cross-sectional data. serologyData <- with(campylobacterSimMediumData, data.frame( IgG = IgG.ratio.new, IgM = IgM.ratio.new, IgA = IgA.ratio.new)) # 2. Define longitudinal response data responseParams <- campylobacterDelftParams3 # 3. Define cut-offs cutOffs <- list(IgG = 0.25, IgM = 0.25, IgA = 0.25) # 4. Baseline distributions baseLine <- list(IgG = c(log(0.05), 1), IgM = c(log(0.005), 1), IgA = c(log(0.005), 1)) # 4a. Calculate a single seroincidence rate for all serum samples... seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG", "IgM", "IgA"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 4b. ...or calculate a single seroincidence rate for a single serum sample # (triplet of titres)... seroincidenceData <- estimateSeroincidence( data = serologyData[1, ], antibodies = c("IgG", "IgM", "IgA"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 4c. ...or calculate a single seroincidence rate for all serum samples (only IgG) seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 5a. Produce summary of the results with 2.5% and 97.5% bounds... summary(seroincidenceData) # 5b. ...or produce summary of the results with 5% and 95% bounds, do not show # convergence... summary(seroincidenceData, quantiles = c(0.05, 0.95), showConvergence = FALSE) # 5c. ...or produce summary and assign to an object... seroincidenceSummary <- summary(seroincidenceData) # ...and work with the results object from now on (here: display the results). seroincidenceSummary$Results ``` \newpage # Acknowledgements Project funded by European Centre for Disease Prevention and Control (ECDC). # References seroincidence/inst/doc/methodology.pdf0000644000176200001440000023722613305535606017655 0ustar liggesusers%PDF-1.5 % 1 0 obj << /Type /ObjStm /Length 3306 /Filter /FlateDecode /N 53 /First 417 >> stream xZ[s6~_ AΝNf8&ԗ$M'DldDR-4 <88,f3R1ͬ0g%,Ms,c)K%Z4X` DCY,g,ꢜfuΞ[ĉ PgcO!<ώ{Q_ p6U6^~󽜍+r|r<>{}QVu5W5K#!h~{>=㢞FrDds4)VztﴹU7t}VKi3[H͋r>a^FzO 0t?TNo4@Hb2tAzZӺ""{^^c?b%_?̫r>yy]>i1\*gѨƬ5hI~]g]ӵ Q*$3\0xq7dV|2!`ڶJ'ѨloU*(f_O0G2PtZ|ma:yuu7`9Ə=j6aE\(.K6p5_מb nE&IP$$ dHXDJB0=btۖ?J^ֻI_g-73[9㳺8l4s>erG'd9<7<̳ ϯGl eA~wO{fzie(,lDcz&u>>^m#tp,V_*W5&-geϬYX5D)ԯu`6m-N6Xcz/ /MM$&M MjڜkI#dB"OOklclЭ̪ךZ\(p*:Y%fL U<~&-32Ot}O=zwPs*3tI^U| :v9҅_UhgR 9oy)S鬁Bn{ %Tn۠6OWb-w"8a--uQӬƆ+4%DƋY1-~YLavfeF[(=0:U;iko 'GZ !$ۥ!M6+:jkm0&㢺d7Kg85:Ӣu~:t6OA-}ߠnoΤ#!FORw7Y{zHhT[[hRDЪN[|ߺ ˗{?̊lrpmݭ6ų G6*@p;-kKRQgY͛79ipmGm-觷' < Է_5Բ6]uko'  \ hmSXfTzecF!f3Bgf0g٤lb񒇆šo˚pm~k#CEa*JVk/we.}{#';cE{PkF)R5MP%N_0^;߿ׯ{!{`%1|:5(yYs4X^2q,q&J[,6λL%6dL2a!x0lBGY?Tg??I]("W#X'Ihd)G+ [nqv\yJ(%^CgA٢C sitzkTe(piŐ3 in(=>Ca.r1$`WQP0i+<8s20÷Ü}_ģGf<@vAc#n[esz6nUs[a?;QgT+agendstream endobj 55 0 obj << /Subtype /XML /Type /Metadata /Length 1647 >> stream GPL Ghostscript 9.23 2018-06-05T17:08:55+02:00 2018-06-05T17:08:55+02:00 LaTeX with hyperref package Seroincidence package methodologyEuropean Centre for Disease Prevention and Control (ECDC) endstream endobj 56 0 obj << /Type /ObjStm /Length 2524 /Filter /FlateDecode /N 52 /First 418 >> stream xZiSH?J#l6c2ݩ|p̀M"me T%>O fSȌ .B)&Ei&&Y&c[ɜg2DWt) 4ii+"` wl-ӑ3R32^YM2+bA25 wHì'-LX ]VQ,SF Nֱ='"(,zb4ҞĐw%@3Bh)Q 9D4qHA@o/^0~/J;Ո 2F77#'fi\ݚ矙M^\旗Bhr\ <&l5F}9SXwUW45m5Km]Akͼˇ8 X89Dw'v",$_~-uvB-cfvp7vbV$u74ъ[h5g/Sd_eOmf/gYSb7,J&k445qGftV.HoB%P+=ٴ/ F.qp_K@xX-ۦ7$_0՗*CLlrC]Nk_=8Ӊ12Q' Wub;KyzțVuZJnOEo2KM~*tO^,m9Cޑl~k$&4d(|B̠shEц5f4Sd#=&E)2eAڌvyR/?z~woGTQ~u3좘^1~^LwbqX5f!I8yqW%&ގ9>~IQ#*΋@p$cI֕ѽuh!B'ԣp;ִՂMbp뼸n`p?c>?;@K~Y|׻| @$0Φ9yG&,yza|Q|V˿f"հ| ѿ܎?[6>[^rAٛ\lZZڸ%j5# -.Q]#AD806B"!Lw(RC/Bj;cry82O)]A%d\[Hѱ5y1Bz-Z5K4U4#MQDwͪ 1,#9d=Ub̺7Tzz D?d]m 2]+&`*3ق+ac8@YXme,cb$DEP@n~{}u⤨UԗZ4ԣն:#wҁXl!6{MQ H^LI.wK8E-_r2;zivƓi'v$St*P0&TV~ё$|xD=۾Ŷ1݃0鏛n>2 fl0HCmh ՔFV&(yf>\o67ޝ@r=m 2# ζquj PqBq40A, ?|.@*d:~B2*KZ^˰֘#*s>pJP+ &3GwP 7%C(3YѾMV FV-I {U i@i ܜU hi#Gn YMVffOBu1[VEؕH^ReSDWVMn/fE6_qS&d]qfHM&B&91=qUP:g|cjt H[9Kѫ|Qe7}V>dv8xإiQOl,$/ ՑȌB>|!WOHCVoH_us: rKM $]BcCjB;6ׯΏ;'Uz͎jJҿFԲС*9EY'tUZL&q52+>4jQ`˨GkѬ[К˕jJoT@>o1?gK~J͗/}?˵¶svMzІuu%M<^V$YE4M1mt|2'+yY <\-GVJdR{wendstream endobj 109 0 obj << /Filter /FlateDecode /Length 4392 >> stream x[Kqsk} yѪCa)BR(EDa8Cn\;3QU] ` 1Q߮XW w[=}{*xXFH⪗ʈ0XY{p}v-YP8{ƥ?_ 2z縖~/7k3{KX nK]TMeW>zSM"-gՔD>r{o1޽^m^o p Ee'k) ?v'M>UNѴ^8`˦ A⯷DrOQv1Sى,}z}6xI7F. i=K'R(3H P'a([YA u4),N}F\{v7s- {<Hg|; Nwg{ݯD*')Vz\oԈwdP @ĮBZoq𗆣(kzT }nz$mw|"(QFf64OHs(-A *lXVy;@ݩ`9Qp%1^²pnaqnP2#U»NgȥStfBN[ed@2-edDzv34n?\~?"%TMGL5d?8 NĚSt\pD ^л̭DzxBB u_, M h$\ H2T0 Ey)7헤 P o ɛyrg,q号!^ak-hTVfSJEuAQk ?ՠK:V>L Wc!$86#xc"6DB4Yh1N(cU0^s}~7ncYp=PReNRSpHDyFeGa2Kbq=-ǰf?_OG=ɬTiRK pSmHaDCL%ŠJQP/aYP!::tgN|S2Upz#1L!t̋5^0rcq$|+JQ"N.('GLSbʸx?ŭqR͍2> gjFI!m^}]_p4]!7:!Tp,dZN99?AF*Ca;|ԣk)&:7}*{cH Gah#o1GQ  Pܿbi = Mr Y|So^AN xhHQt+` k!0 e%trIw@&_N2`-]Q;=ﮥAw)6r$ ZSdUs~!nn,I3O!`S8nf1`mUd~RcɖWsX!R ']WŰ_A8+E8']1eBvS}K)>) t_hpu>KbW.C@:D:ܧ8@DD=;>T+ ȲPL@4]ZE[M>E^(bael-DŽL m9~nQ.BΛ VXQ&ڂ@~KRM{>eĮ0-µ,U鰌&'$`$cOe҄Ksxje ȶ(HDyglS/ҥ $:H.[@Qߝw7ZFy|i897%uu$]4fe%U?}");K ?)މbsԬJ.ig#_SV L uq-=x8B|4B:4Zz.ҁ d]9^ǕCa[۶#A̫xt X;6>e5ҌtaPk?OF *tdڢeN|?$6K axpJ/J}kzA*w2ὀ.#q8 ɒ $D9jJ< !kNjW0 SNA]"sjOE1 :B  y6hFUi'_ReӜcPDy[?6 }Wkgr.ZkkMLg;1? 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%\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} pkgVersion <- packageDescription("seroincidence")$Version pkgLicense <- packageDescription("seroincidence")$License pkgDate <- packageDescription("seroincidence")$Date authorsString <- gsub("^ *|(?<= ) |\n| *$", "", packageDescription("seroincidence")$Authors, perl = TRUE) authorList <- eval(parse(text = authorsString)) pkgAuthors <- paste(format(authorList, include = c("given", "family", "email", "comment"), braces = list(family = c("", ",
"), email = c("<", ">,
"), comment = c("", ""))), collapse = "

") pkgMaintainer <- packageDescription("seroincidence")$Maintainer pkgBaseFileName <- paste("seroincidence", pkgVersion, sep = "_") pkgUrl <- packageDescription("seroincidence")$URL ``` R package **seroincidence** allows translation of antibody levels measured in a (cross-sectional) population sample into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. Item | Data ----- | ------ Version | `r pkgVersion` Published | `r pkgDate` Authors | `r pkgAuthors` Maintainer | `r pkgMaintainer` License | `r pkgLicense` Installation manual | [installation.pdf](installation.pdf) Tutorial | [tutorial.pdf](tutorial.pdf) Appendix | [methodology.pdf](methodology.pdf) ECDC web site | `r pkgUrl` seroincidence/NAMESPACE0000644000176200001440000000056213302455573014315 0ustar liggesusers# Generated by roxygen2: do not edit by hand S3method(print,seroincidence) S3method(print,summary.seroincidence) S3method(summary,seroincidence) export(estimateSeroincidence) export(getAdditionalData) importFrom(stats,dlnorm) importFrom(stats,optim) importFrom(stats,pgamma) importFrom(stats,plnorm) importFrom(utils,download.file) importFrom(utils,unzip) seroincidence/NEWS0000644000176200001440000000633713305436415013600 0ustar liggesusersseroincidence v.2.0.0 (Release date: 2018-06-05) ================ Changes: * A complete rewrite of the methodology and the implementation. seroincidence v.1.0.5 (Release date: 2015-12-29) ================ Changes: * Packages "stats" and "utils" listed in the "Imports" section of DESCRIPTION. Imported functions are called as "pkg::fun()". * Vignette "methodology.Rmd" made compatible with rmarkdown 0.9. Line "- \usepackage[pdftex]{graphicx}" removed. * Oxygen documentation made compatible with roxygen2 5.0.1. Values for tags "docType" and "news" put on the same line. seroincidence v.1.0.4 (Release date: 2015-05-22) ================ Changes: * URL for package location on ECDC website updated. seroincidence v.1.0.3 (Release date: 2015-04-10) ================ Changes: * LICENSE file removed, reference to that file removed from DESCRIPTION * NEWS updated * changed the version numbering from 1.0.2 to 1.0.3. seroincidence v.1.0.2 (Release date: 2015-04-09) ================ Changes: * manually corrected break line in URL in DESCRIPTION file in the source package "tar.gz" file (inserted there by the R build system). * ensured that all references to URL from DESCRIPTION (in citation, vignettes) have all break lines removed. * fixed one reference in the vignettes. * changed the version numbering from 1.0.1 to 1.0.2. seroincidence v.1.0.1 (Release date: 2015-03-31) ================ Changes: * All titles (package, functions, data sets) changed to title case * All S3 methods exported and registered * All exported functions/data sets are documented with examples including comments. Examples requiring time consuming calculations are put in \dontrun environment. seroincidence v.1.0.0 (Release date: 2015-03-18) ================ Changes: * Vignettes reformatted seroincidence v.0.9.9 (Release date: 2015-03-04) ================ Changes: * Vignette's content updated seroincidence v.0.9.8 (Release date: 2015-02-25) ================ Changes: * "Methodology" document extracted from the tutorial and converted to pdf. * Fixes of typos in the methodology document. * Fixes of typos, formatting, references, additional text in the tutorial. * Restructuring and additional text in the installation manual. * Acronym "GUI" expanded to "graphical user interface". * Description of parametric models in "simulateSerologyData.R", "simulateSalmonellaResponseParams" and the tutorial. * Description of response parameters added in the tutorial (section "Specifying longitudinal response parameters"). * Description of outputs of the summary function in the tutorial. * Spell check run on the installation, tutorial and methodology. seroincidence v.0.9.7 (Release date: 2015-01-30) ================ Changes: * Tutorial vignettes customized for pdf and html output * Sections "Antibody decay and seroincidence" of the tutorial vignettes include now subsections on censoring and checks. seroincidence v.0.9.6 (Release date: 2014-12-19) ================ Changes: * Fix intialization of variable "progressBarCreated" in "estimateSeroincidence". * Added URL to ECDC website * "estimateSeroincidence" and "summary.seroincidence" updated: operate on output of "optim" function. * printing functions added for outputs of "estimateSeroincidence" and "summary.seroincidence" seroincidence/data/0000755000176200001440000000000013305523615014000 5ustar liggesusersseroincidence/data/serologyData.RData0000644000176200001440000017727013303571700017364 0ustar liggesusers7zXZi"6!X+])TW"nRʟu,=!zPب[P/*sf Y'H-T뫹)nHo etԹE*RMZ|aU0y >Ƞ3^y]/oS:;_ ٕ͇2-1_tzUG^H@IRrM驧~/m rTL^?嘴X8^Y I3{n%4M \%kmCþe>zLY4Q d+IܙVëTtW+@ss?vИs+͊Vk8Lpx, (i.!Un 5iJ^t@oO1$ut. *8;(|@b^0*Rn;,X~hlS l' &'_/';) 00hļ$ZzJxk[)ǑLHD4Kfɪ Vk_dC#e J'U۲RwEIR5OerGAM1(h5D}ml1ߘ S[\J~-4ګҥN"fجHD"mriWG4/}@񠤼n5 A`Y!oeҾd}OnoQBcv|O#|eX %n \{{2l[4J΂UeET5t*0;nYhT`=U2!r(n M{鍂H<(Ybl0y;[ gEm~!?{=y>8Fi>MO. 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MV|zatxcĕ*TTreNvAb_k&krtUxepX52mG2C;7ΒxzDv4 2KҊ+Ƹ1?l}7)Ex"ͺUz5MɂD,h4cm#P(kᡕ+WA'[LgW;[FߞsW|g;ޏ I"}@[CH}RxaNx7gb`qTqe@q+F) J=ɟ@$YcO@hůO٪niWCXǾ^NStFg;OvL>[ӎ7ycTZcﮤm#S0'ϼf'5qV.qԇt8Q+!ׄړ%5{P?W%NACeo~He/xe﷧s;HY0;zD #vWV71mRl{gh1-3mQ9av?C͒ǀ3?i4B,)S Uq74 c<4cJ\)Bo"n]EQked^w:mRo@m0 #(ix y&d&+86h?3O * -C5ϯZK2>Ilx@"H*S\ 4,Ci_m#Z LѨ:kLs{EK%oDH}=DM.gdՆ˧kHHS{Znsޱ Yhn/#ć{]%zj _{* 9^0@G놈(f%@P p/>s ^&ci#"_Ӏb+RR@cˍ#FE ={qRI*pdh*BW\0hȠk=?ŕFUg|bˑXux;PIUT5:ۃhbE*֛k ]xO[Fj8. jel,5|rkLJF1=[& D!8HƵ6uVmGŻKl<ũf)F B>F_nR.$Š|A5 0AV ^h!i|fWp@C@ت\<Ɵ(ȥٛQ@YZseroincidence/data/datalist0000644000176200001440000000073113305523615015531 0ustar liggesusersresponseParams: campylobacterDelftParams1 campylobacterDelftParams3 campylobacterDelftParams4 campylobacterSSIParams1 campylobacterSSIParams2 campylobacterSSIParams4 pertussisIgGPTParams1 pertussisIgGPTParams2 pertussisIgGPTParams3 pertussisIgGPTParams4 salmonellaSSIParams1 salmonellaSSIParams2 salmonellaSSIParams4 serologyData: campylobacterSimHighData campylobacterSimLowData campylobacterSimMediumData pertussisSimHighData pertussisSimLowData pertussisSimMediumData seroincidence/R/0000755000176200001440000000000013304777066013302 5ustar liggesusersseroincidence/R/print.seroincidence.R0000644000176200001440000000314413273375665017400 0ustar liggesusers#' @title #' Print Method for Seroincidence Object #' #' @description #' Custom \code{\link{print}} function to show output of the seroincidence calculator \code{\link{estimateSeroincidence}}. #' #' @param x A list containing output of function \code{\link{estimateSeroincidence}}. #' @param ... Additional arguments affecting the summary produced. #' #' @examples #' #' \dontrun{ #' # estimate seroincidence #' seroincidence <- estimateSeroincidence(...) #' #' # print the seroincidence object to the console #' print(seroincidence) #' #' # or simply type (appropriate print method will be invoked automatically) #' seroincidence #' } #' #' @export print.seroincidence <- function(x, ...) { cat("Seroincidence object estimated given the following setup:\n") cat(paste("a) Antibodies :", paste(x[["Antibodies"]], collapse = ", ")), "\n") cat(paste("b) Strata :", paste(x[["Strata"]], collapse = ", ")), "\n") censorLimits <- x[["CensorLimits"]] cat(paste("c) Censor limits:", paste(sapply(names(censorLimits), FUN = function(name) { paste(name, censorLimits[name], sep = " = ") }), collapse = ", "), "\n")) cat("\n") cat("This object is a list containing the following items:\n") cat("Fits - List of outputs of \"optim\" function per stratum.\n") cat("Antibodies - Input parameter antibodies of function \"estimateSeroincidence\".\n") cat("Strata - Input parameter strata of function \"estimateSeroincidence\".\n") cat("CensorLimits - Input parameter censorLimits of function \"estimateSeroincidence\".\n") cat("\n") cat("Call summary function to obtain output results.\n") } seroincidence/R/seroincidence-package.R0000644000176200001440000001247613302455573017634 0ustar liggesusers#' @docType package #' #' @name seroincidence #' #' @aliases seroincidence seroincidence-package #' #' @title #' Estimating Infection Rates from Serological Data #' #' @description #' Translates antibody levels measured in a (cross-sectional) population sample into an #' estimate of the frequency with which seroconversions (infections) occur in the sampled population. #' #' @details #' For detailed documentation type the following in the R console:\cr #' #' \code{vignette("installation", package = "seroincidence")}\cr #' \code{vignette("tutorial", package = "seroincidence")}\cr #' \code{vignette("methodology", package = "seroincidence")} #' #' @author #' Author: Peter Teunis \email{}\cr #' Author: Jan van Eijkeren\cr #' Contributor: Daniel Lewandowski \email{}\cr #' Maintainer: Chantal Quinten \email{} #' #' @references #' #' \strong{\emph{Methods for estimating seroincidence}} #' #' \itemize{ #' \item Teunis, P. F., van Eijkeren, J. C., Ang, C. W., van Duynhoven, Y. T., Simonsen, J. B., Strid, M. A., van Pelt, W.\cr #' "Biomarker dynamics: estimating infection rates from serological data"\cr #' Statistics in Medicine 31, no. 20 (September 9, 2012): 2240--48. doi:10.1002/sim.5322. #' #' \item Simonsen, J., Molbak, K., Falkenhorst, G., Krogfelt, K. A., Linneberg, A., Teunis, P. F.\cr #' "Estimation of incidences of infectious diseases based on antibody measurements"\cr #' Statistics in Medicine 28, no. 14 (June 30, 2009): 1882--95. doi:10.1002/sim.3592. #' } #' #' \strong{\emph{Applications}} #' #' \itemize{ #' #' \item Monge, S., Teunis, P. F., Friesema, I., Franz, E., Ang, W., van Pelt, W., Mughini-Gras, L.\cr #' "Immune response-eliciting exposure to Campylobacter vastly exceeds the incidence of clinically #' overt campylobacteriosis but is associated with similar risk factors: A nationwide serosurvey in the Netherlands"\cr #' Journal of Infection, 2018, 1--7, doi:10.1016/j.jinf.2018.04.016 #' #' \item Kretzschmar, M., Teunis, P. F., Pebody, R. G.\cr #' "Incidence and reproduction numbers of pertussis: estimates from serological and social contact data in five European countries"\cr #' PLoS Medicine 7, no. 6 (June 1, 2010):e1000291. doi:10.1371/journal.pmed.1000291. #' #' \item Simonsen, J., Strid, M. A., Molbak, K., Krogfelt, K. A., Linneberg, A., Teunis, P.\cr #' "Sero-epidemiology as a tool to study the incidence of Salmonella infections in humans"\cr #' Epidemiology and Infection 136, no. 7 (July 1, 2008): 895--902. doi:10.1017/S0950268807009314 #' #' \item Simonsen, J., Teunis, P. F., van Pelt, W., van Duynhoven, Y., Krogfelt, K. A., Sadkowska-Todys, M., Molbak K.\cr #' "Usefulness of seroconversion rates for comparing infection pressures between countries"\cr #' Epidemiology and Infection, April 12, 2010, 1--8. doi:10.1017/S0950268810000750. #' #' \item Falkenhorst, G., Simonsen, J., Ceper, T. H., van Pelt, W., de Valk, H., Sadkowska-Todys, M., Zota, L., Kuusi, M., Jernberg, C., Rota, M. C., van Duynhoven, Y. T., Teunis, P. F., Krogfelt, K. A., Molbak, K.\cr #' "Serological cross-sectional studies on salmonella incidence in eight European countries: no correlation with incidence of reported cases"\cr #' BMC Public Health 12, no. 1 (July 15, 2012): 523--23. doi:10.1186/1471-2458-12-523. #' #' \item Teunis, P. F., Falkenhorst, G., Ang, C. W., Strid, M. A., De Valk, H., Sadkowska-Todys, M., Zota, L., Kuusi, M., Rota, M. C., Simonsen, J. B., Molbak, K., Van Duynhoven, Y. T., van Pelt, W.\cr #' "Campylobacter seroconversion rates in selected countries in the European Union"\cr #' Epidemiology and Infection 141, no. 10 (2013): 2051--57. doi:10.1017/S0950268812002774. #' #' \item de Melker, H. E., Versteegh, F. G., Schellekens, J. F., Teunis, P. F., Kretzschmar, M.\cr #' "The incidence of Bordetella pertussis infections estimated in the population from a combination of serological surveys"\cr #' The Journal of Infection 53, no. 2 (August 1, 2006): 106--13. doi:10.1016/j.jinf.2005.10.020 #' } #' #' \strong{\emph{Quantification of seroresponse}} #' #' \itemize{ #' \item de Graaf, W. F., Kretzschmar, M. E., Teunis, P. F., Diekmann, O.\cr #' "A two-phase within-host model for immune response and its application to serological profiles of pertussis"\cr #' Epidemics 9 (2014):1--7. doi:10.1016/j.epidem.2014.08.002. #' #' \item Berbers, G. A., van de Wetering, M. S., van Gageldonk, P. G., Schellekens, J. F., Versteegh, F. G., Teunis, P.F.\cr #' "A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens"\cr #' Vaccine 31, no. 36 (August 12, 2013): 3732--38. doi:10.1016/j.vaccine.2013.05.073. #' #' \item Versteegh, F. G., Mertens, P. L., de Melker, H. E., Roord, J. J., Schellekens, J. F., Teunis, P. F.\cr #' "Age-specific long-term course of IgG antibodies to pertussis toxin after symptomatic infection with Bordetella pertussis"\cr #' Epidemiology and Infection 133, no. 4 (August 1, 2005): 737--48. #' #' \item Teunis, P. F., van der Heijden, O. G., de Melker, H. E., Schellekens, J. F., Versteegh, F. G., Kretzschmar, M. E. #' "Kinetics of the IgG antibody response to pertussis toxin after infection with B. pertussis"\cr #' Epidemiology and Infection 129, no. 3 (December 10, 2002):479. doi:10.1017/S0950268802007896. #' } #' #' @importFrom stats dlnorm optim pgamma plnorm #' @importFrom utils download.file unzip NULL seroincidence/R/utils.R0000644000176200001440000001230313303571700014546 0ustar liggesusers.pasteN <- function(...) { paste(..., sep = "\n") } .appendNames <- function(abNames) { res <- c() for (k in seq_len(length(abNames))) { res <- c(res, paste0(abNames[k], ".lo"), paste0(abNames[k], ".hi")) } return(res) } .stripNames <- function(abNames) { if (grepl(".", abNames, fixed = TRUE)) { return(substr(abNames, 1, nchar(abNames) - 3)) } return(abNames) } .errorCheck <- function(data, antibodies, strata, params) { .checkAntibodies(antibodies = antibodies) .checkCsData(data = data, antibodies = antibodies) .checkStrata(data = data, strata = strata) .checkParams(antibodies = antibodies, params = params) invisible(NULL) } .checkAntibodies <- function(antibodies) { stopifnot(!missing(antibodies)) if (!is.character(antibodies)) { stop(.pasteN("Argument \"antibodies\" is not a character vector.", "Provide a character vector with at least one antibody name.")) } if (all(antibodies == "")) { stop(.pasteN("Argument \"antibodies\" is empty.", "Provide a character vector with at least one antibody name.")) } invisible(NULL) } .checkCsData <- function(data, antibodies) { if (!is.data.frame(data)) { stop(.pasteN("Argument \"data\" is not a dataframe.", "Provide a dataframe with cross-sectional serology data per antibody.")) } if (!is.element("Age", names(data))) { stop("Argument \"data\" is missing column \"Age\".") } if (!all(is.element(.checkIvc(data, antibodies)$Antibodies, names(data)))) { stop("Antibody names in argument \"data\" and argument \"antibodies\" do not match.") } invisible(NULL) } .checkIvc <- function(data, antibodies) { # Assume we are not dealing with interval censored data ivc <- FALSE if (length(intersect(names(data), antibodies)) != length(antibodies)) { # Add .lo and .hi to ab names antibodies <- .appendNames(antibodies) # We are dealing with interval censored data ivc <- TRUE } return(list(Ivc = ivc, Antibodies = antibodies)) } .checkParams <- function(antibodies, params) { if (!is.list(params)) { stop(.pasteN("Argument \"params\" is not a list of dataframes.", "Provide a list of three dataframes with names of the antibodies to be tested.", "Each of the dataframes should contain a Monte Carlo sample of the longitudinal", "parameters named y1, alpha, r, y0, mu1 and t1.")) } if (!all(sapply(params, is.data.frame))) { stop(.pasteN("Argument \"params\" is not a list of dataframes.", "Provide a list of three dataframes with names of the antibodies to be tested.", "Each of the dataframes should contain a Monte Carlo sample of the longitudinal", "parameters named y1, alpha, r, y0, mu1 and t1.")) } if (!all(is.element(names(params[[1]]), c("y1", "alpha", "yb", "r", "y0", "mu1", "t1")))) { stop(.pasteN("The parameter names do not match.", "Provide a list of three dataframes with names of the antibodies to be tested.", "Each of the dataframes should contain a Monte Carlo sample of the longitudinal", "parameters named y1, alpha, r, y0, mu1 and t1.")) } if (length(params[[1]]$y0) != length(params[[1]]$alpha) | length(params[[1]]$y0) != length(params[[1]]$yb) | length(params[[1]]$y0) != length(params[[1]]$r) | length(params[[1]]$y0) != length(params[[1]]$y1) | length(params[[1]]$y0) != length(params[[1]]$mu1) | length(params[[1]]$y0) != length(params[[1]]$t1)) { stop("The parameter lists \"params\" are of different length.") } if (!all(is.element(antibodies, names(params)))) { stop("Antibody names in argument \"antibodies\" and argument \"params\" do not match.") } invisible(NULL) } .checkStrata <- function(data, strata) { if (!is.character(strata)) { stop(.pasteN("Argument \"strata\" is not a character vector.", "Provide a character vector with strata names.")) } if (!all(is.element(strata, union("", names(data))))) { stop("Strata names in argument \"data\" and argument \"strata\" do not match.") } invisible(NULL) } .prepData <- function(data, antibodies, strata = "") { ivcAb <- .checkIvc(data, antibodies) # Make stratum variable (if needed) dataStrata <- .makeStrata(data, strata) levelsStrata <- levels(dataStrata$Stratum) return(list(Ivc = ivcAb$Ivc, Antibodies = ivcAb$Antibodies, Levels = levelsStrata, Data = dataStrata)) } .makeStrata <- function(data, strata = "") { dataStrata <- data if (all(strata != "")) { dataStrata$Stratum <- interaction(dataStrata[, strata]) } else { dataStrata$Stratum <- factor(1) } return(dataStrata) } .selectModel <- function(param) { model1 <- any(param$r == 1 & param$yb == 0 & param$t1 == 0) model2 <- any(param$r != 1 & param$yb == 0 & param$t1 == 0) model3 <- any(param$r == 1 & !is.na(param$y0)) model4 <- any(param$r != 1 & !is.na(param$y0)) model5 <- any(param$r == 1 & param$yb != 0 & param$t1 == 0) res <- which(c(model1, model2, model3, model4, model5)) if (length(res) == 0) { res <- 0 } return(res) } seroincidence/R/tau-funcs.R0000644000176200001440000000364013272107427015325 0ustar liggesusers.tau1 <- function(y, age, param) { y1 <- param$y1 alpha <- param$alpha if (is.na(age)) { return(y <= y1) } tm <- log(y1 / y) / alpha return(tm < age & y <= y1) } .tau2 <- function(y, age, param) { y1 <- param$y1 alpha <- param$alpha r <- param$r if (is.na(age)) { return(y <= y1) } tm <- (y1^(1 - r) - y^(1 - r)) / (alpha * (1 - r)) return(tm < age & y <= y1) } .tau30 <- function(y, age, param) { y0 <- param$y0 return(y < y0) } .tau31 <- function(y, age, param) { y0 <- param$y0 mu1 <- param$mu1 y1 <- param$y1 if (is.na(age)) { return(y >= y0 & y < y1) } tm <- log(y / y0)/mu1 return(tm < age & y >= y0 & y < y1) } .tau32 <- function(y, age, param) { y1 <- param$y1 alpha <- param$alpha t1 <- param$t1 if (is.na(age)) { return(y <= y1) } tm <- t1 + log(y1 / y) / alpha return(tm < age & y <= y1) } .tau33 <- function(y, age, param) { y1 <- param$y1 t1 <- param$t1 if (is.na(age)) { return(y > y1) } return(t1 > age & y > y1) } .tau40 <- function(y, age, param) { y0 <- param$y0 return(y < y0) } .tau41 <- function(y, age, param) { y0 <- param$y0 mu1 <- param$mu1 y1 <- param$y1 if (is.na(age)) { return(y >= y0 & y < y1) } tm <- log(y / y0) / mu1 return(tm < age & y >= y0 & y < y1) } .tau42 <- function(y, age, param) { y1 <- param$y1 alpha <- param$alpha r <- param$r t1 <- param$t1 if (is.na(age)) { return(y <= y1) } tm <- t1 + (y1^(1 - r) - y^(1 - r)) / (alpha * (1 - r)) return(tm < age & y <= y1) } .tau43 <- function(y, age, param) { y1 <- param$y1 t1 <- param$t1 if (is.na(age)) { return(y > y1) } return(t1 > age & y > y1) } .tau5 <- function(y, age, param) { y1 <- param$y1 alpha <- param$alpha yb <- param$yb if (is.na(age)) { return(y > yb & y <= y1) } tm <- y1 / (y - yb) tm[y <= yb] <- 1 tm <- log(tm) / alpha return(tm < age & y > yb & y <= y1) } seroincidence/R/nllByType.R0000644000176200001440000000336013304777066015351 0ustar liggesusers.nllByType <- function(data, param, censorLimit, ivc = FALSE, m = 0, par0, start, modelType) { lambda <- exp(start) pdfModel <- switch(modelType, "1" = .rhoPdf1, "2" = .rhoPdf2, "3" = .rhoPdf3, "4" = .rhoPdf4, "5" = .rhoPdf5) cdfModel <- switch(modelType, "1" = .rhoCdf1, "2" = .rhoCdf2, "3" = .rhoCdf3, "4" = .rhoCdf4, "5" = .rhoCdf5) if (ivc) { # data must have .hi and .lo observations rho <- apply(X = data, MARGIN = 1, FUN = .deltaFunc, lambda = lambda, m = m, param = param, fun = cdfModel, par0 = par0) # Remove empty outcomes rho <- rho[rho != 0] return(-sum(log(rho))) } # Deal with uncensored data dataUncens <- data[data[, 1] > censorLimit, ] if (length(dataUncens) == 2) { dataUncens <- as.matrix(t(dataUncens)) } rho <- numeric(0) if (length(dataUncens) > 0) { rhoUc <- apply(X = dataUncens, MARGIN = 1, FUN = .densFunc, lambda = lambda, m = m, param = param, fun = pdfModel, par0 = par0) rho <- c(rho, rhoUc) } # Deal with censored data dataCens <- data[data[, 1] <= censorLimit, ] if (length(dataCens) == 2) { dataCens[1] <- censorLimit dataCens <- as.matrix(t(dataCens)) } if (length(dataCens) > 2) { dataCens[, 1] <- censorLimit } if (length(dataCens) > 0) { rhoCn <- apply(X = dataCens, MARGIN = 1, FUN = .densFunc, lambda = lambda, m = m, param = param, fun = cdfModel, par0 = par0) rho <- c(rho, rhoCn) } # Remove empty outcomes rho <- rho[!is.na(rho) & rho != 0] return(-sum(log(rho))) } seroincidence/R/nll.R0000644000176200001440000000271313304777066014215 0ustar liggesusers.nll <- function(stratumData, antibodies, params, censorLimits, ivc = FALSE, m = 0, par0, start) { # Start with zero total nllTotal <- 0 if (ivc) { # Loop over antibodies for (abIdx in seq_along(antibodies)) { antibody <- .stripNames(antibodies[abIdx]) param <- params[[antibody]] p0 <- par0[[antibody]] modelType <- .selectModel(param) data <- cbind(stratumData[[antibodies[abIdx]]], stratumData[[antibodies[abIdx + 1]]], stratumData$Age) nllSingle <- .nllByType(data = data, param = param, censorLimit = NULL, ivc = ivc, m = m, par0 = p0, start = start, modelType = modelType) if (!is.na(nllSingle)) { nllTotal <- nllTotal + nllSingle } } } else { # Loop over antibodies for (abIdx in seq_along(antibodies)) { antibody <- .stripNames(antibodies[abIdx]) param <- params[[antibody]] p0 <- par0[[antibody]] censorLimit <- censorLimits[[antibody]] modelType <- .selectModel(param) data <- cbind(stratumData[[antibodies[abIdx]]], stratumData$Age) nllSingle <- .nllByType(data = data, param = param, censorLimit = censorLimit, ivc = ivc, m = m, par0 = p0, start = start, modelType = modelType) if (!is.na(nllSingle)) { nllTotal <- nllTotal + nllSingle } } } # Return total log-likelihood return(nllTotal) } seroincidence/R/estimateSeroincidence.R0000644000176200001440000001040413305423144017714 0ustar liggesusers#' Estimate Seroincidence #' #' Function to estimate seroincidences based on cross-section serology data and longitudinal #' response model. #' #' @param data Data frame with cross-sectional serology data per antibody and age, and additional #' columns to identify possible \code{strata}. #' @param antibodies Character vector with one or more antibody names. Values must match \code{data}. #' @param strata Character vector of strata. Values must match with \code{data}. Default = "". #' @param params List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' @param censorLimits List of cutoffs for one or more named antibody types (corresponding to #' \code{data}). #' @param par0 List of parameters for the (lognormal) distribution of antibody concentrations #' for true seronegatives (i.e. those who never seroconverted), by named antibody type #' (corresponding to \code{data}). #' @param start A starting value for \code{log(lambda)}. Value of -6 corresponds roughly to 1 day #' (log(1/365.25)), -4 corresponds roughly to 1 week (log(7 / 365.25)). Default = -6. #' @param numCores Number of processor cores to use for calculations when computing by strata. If #' set to more than 1 and package \pkg{parallel} is available, then the computations are #' executed in parallel. Default = 1L. #' #' @return #' A set of lambda estimates for each strata. #' #' @examples #' #' \dontrun{ #' estimateSeroincidence(data = csData, #' antibodies = c("IgG", "IgM", "IgA"), #' strata = "", #' params = campylobacterDelftParams4, #' censorLimits = cutOffs, #' par0 = baseLn, #' start = -4) #' #' estimateSeroincidence(data = csData, #' antibodies = c("IgG", "IgM", "IgA"), #' strata = "", #' params = campylobacterDelftParams4, #' censorLimits = cutOffs, #' par0 = baseLn, #' start = -4, #' numCores = parallel::detectCores()) #' } #' #' @export estimateSeroincidence <- function( data, antibodies, strata = "", params, censorLimits, par0, start = -6, numCores = 1L) { if (!"Age" %in% names(data)) { data$Age <- rep(NA, nrow(data)) } .errorCheck(data = data, antibodies = antibodies, strata = strata, params = params) antibodiesData <- .prepData(data = data, antibodies = antibodies, strata = strata) ivc <- antibodiesData$Ivc # Split data per stratum stratumDataList <- split(antibodiesData$Data, antibodiesData$Data$Stratum) # Loop over data per stratum if (numCores > 1L && requireNamespace("parallel", quietly = TRUE)) { libPaths <- .libPaths() cl <- parallel::makeCluster(min(numCores, parallel::detectCores())) on.exit({ parallel::stopCluster(cl) }) parallel::clusterExport(cl, c("libPaths"), envir = environment()) parallel::clusterEvalQ(cl, { .libPaths(libPaths) library(seroincidence) }) fits <- parallel::parLapplyLB(cl, stratumDataList, .optNll, antibodies = antibodies, params = params, censorLimits = censorLimits, ivc = ivc, m = 0, par0 = par0, start = start) } else { fits <- lapply(stratumDataList, .optNll, antibodies = antibodies, params = params, censorLimits = censorLimits, ivc = ivc, m = 0, par0 = par0, start = start) } incidenceData <- list(Fits = fits, Antibodies = antibodies, Strata = strata, CensorLimits = censorLimits) class(incidenceData) <- c("seroincidence", "list") return(incidenceData) } seroincidence/R/getAdditionalData.R0000644000176200001440000000446313304210004016744 0ustar liggesusers#' Get Additional Data #' #' Retrieves additional data from internet. This can be any file type, but the purpose of this #' function is to download data such as longitudinal response parameters from an online repository. #' #' @param fileName Name of the file to download. Required. #' @param repoURL Web address of the remote repository of files to download from. Required. #' Default = \code{"http://ecdc.europa.eu/sites/portal/files/documents"} #' @param savePath Folder to save the downloaded and unzipped (if needed) file. File is saved only #' if this argument is not \code{NULL}. Optional. Default = \code{NULL}. #' #' @return #' Data object #' #' @examples #' #' \dontrun{ #' getAdditionalData(fileName = "coxiellaIFAParams4.zip") #' getAdditionalData(fileName = "yersiniaSSIParams4.zip") #' getAdditionalData(fileName = "coxiellaIFAParams4.zip", savePath = getwd()) #' getAdditionalData(fileName = "yersiniaSSIParams4.zip", savePath = getwd()) #' } #' #' @export getAdditionalData <- function( fileName, repoURL = "http://ecdc.europa.eu/sites/portal/files/documents", savePath = NULL) { tmpFileName <- file.path(tempdir(), fileName) on.exit({ unlink(tmpFileName) }) # Download tryCatch({ download.file(file.path(repoURL, fileName), tmpFileName, mode = "wb", quiet = TRUE) }, error = function(e) { print("There is problem with downloading the requested file. Please, check input arguments or the internet connection.") }) # Unzip if (tolower(tools::file_ext(tmpFileName)) == "zip") { fileList <- unzip(tmpFileName, list = TRUE) if (nrow(fileList) == 1) { zipedFileName <- fileList[1, "Name"] if (tolower(tools::file_ext(zipedFileName)) == "rds") { unzip(tmpFileName, exdir = tempdir()) unlink(tmpFileName) tmpFileName <- file.path(tempdir(), zipedFileName) } else { stop("Downloaded zip file does not contain an Rds file.") } } else { stop("Downloaded zip file contains multiple files. It should contain a single Rds file.") } } # Store if (!is.null(savePath)) { dir.create(savePath, showWarnings = FALSE, recursive = TRUE) file.copy(tmpFileName, savePath, overwrite = TRUE, recursive = TRUE) } # Read data <- readRDS(tmpFileName) return(data) } seroincidence/R/print.summary.seroincidence.R0000644000176200001440000000262413272107427021062 0ustar liggesusers#' @title #' Print Method for Seroincidence Summary Object #' #' @description #' Custom \code{\link{print}} function to show output of the seroincidence summary \code{\link{summary.seroincidence}}. #' #' @param x A list containing output of function \code{\link{summary.seroincidence}}. #' @param ... Additional arguments affecting the summary produced. #' #' @examples #' #' \dontrun{ #' # estimate seroincidence #' seroincidence <- estimateSeroincidence(...) #' #' # calculate summary statistics for the seroincidence object #' seroincidenceSummary <- summary(seroincidence) #' #' # print the summary of seroincidence object to the console #' print(seroincidenceSummary) #' #' # or simply type (appropriate print method will be invoked automatically) #' seroincidenceSummary #' } #' #' @export print.summary.seroincidence <- function(x, ...) { cat("Seroincidence estimated given the following setup:\n") cat(paste("a) Antibodies :", paste(x[["Antibodies"]], collapse = ", ")), "\n") cat(paste("b) Strata :", paste(x[["Strata"]], collapse = ", ")), "\n") censorLimits <- x[["CensorLimits"]] cat(paste("c) Censor limits:", paste(sapply(names(censorLimits), FUN = function(name) { paste(name, censorLimits[name], sep = " = ") }), collapse = ", "), "\n")) cat(paste("d) Quantiles :", paste(x[["Quantiles"]], collapse = ", ")), "\n") cat("\n Seroincidence estimates:\n") print(x[["Results"]]) } seroincidence/R/densFunc.R0000644000176200001440000000025613304777066015175 0ustar liggesusers.densFunc <- function(yDat, lambda, m, param, fun, par0) { rho <- fun(y = yDat[1], age = yDat[2], lambda = lambda, m = m, param = param, par0 = par0) return(mean(rho)) } seroincidence/R/rho-funcs.R0000644000176200001440000002134113272107427015322 0ustar liggesusers.rhoCdf <- function(y, par) { return(plnorm(y, meanlog = par[1], sdlog = par[2])) } .rhoCdf1 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau1(y, age, param) for (j in 0:m) { rho[index] <- rho[index] + pgamma(q = log(y1[index] / y) * lambda / alpha[index], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) } rho[index] <- rho[index] / (m + 1) rho[y > y1] <- 1 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoCdf(y, par0) } return(rho[rho != 0]) } .rhoCdf2 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha r <- param$r nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau2(y, age, param) for (j in 0:m) { rho[index] <- rho[index] + pgamma(q = lambda * (y1[index]^(1 - r[index]) - y^(1 - r[index])) / (alpha[index] * (1 - r[index])), shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) } rho[index] <- rho[index] / (m + 1) rho[y > y1] <- 1 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoCdf(y, par0) } return(rho[rho != 0]) } .rhoCdf3 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha y0 <- param$y0 mu1 <- param$mu1 nMc <- length(y1) # Rising branch rho1 <- rep(0, nMc) # Decaying branch rho2 <- rep(0, nMc) if (y <= 0) { return(rho1) } # Then y = y0 in rho1 index0 <- .tau30(y, age, param) # Then y = y in rho1 index1 <- .tau31(y, age, param) # Then y = y in rho2 index2 <- .tau32(y, age, param) # Then y = y1 in rho1 and in rho2 index3 <- .tau33(y, age, param) for (j in 0:m) { rho1[index0] <- rho1[index0] + 1 / factorial(j) rho1[index1] <- rho1[index1] + pgamma(q = lambda * log(y / y0[index1]) / mu1[index1], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho1[index3] <- rho1[index3] + pgamma(q = lambda * log(y1[index3] / y0[index3]) / mu1[index3], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho2[index2] <- rho2[index2] + pgamma(q = (log(y1[index2] / y0[index2]) / mu1[index2] + log(y1[index2] / y) / alpha[index2]) * lambda, shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho2[index3] <- rho2[index3] + pgamma(q = (log(y1[index3] / y0[index3]) / mu1[index3]) * lambda, shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) } rho1 <- 1 - rho1 / (m + 1) rho2 <- rho2 / (m + 1) rho <- rho1 + rho2 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoCdf(y, par0) } return(rho[rho != 0]) } .rhoCdf4 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha r <- param$r y0 <- param$y0 mu1 <- param$mu1 nMc <- length(y1) # Rising branch rho1 <- rep(0, nMc) # Decaying branch rho2 <- rep(0, nMc) if (y <= 0) { return(rho1) } # Then y = y0 in rho1 index0 <- .tau40(y, age, param) # Then y = y in rho1 index1 <- .tau41(y, age, param) # Then y = y in rho2 index2 <- .tau42(y, age, param) # Then y = y1 in rho1 and in rho2 index3 <- .tau43(y, age, param) for (j in 0:m) { rho1[index0] <- rho1[index0] + 1 / factorial(j) rho1[index1] <- rho1[index1] + pgamma(q = lambda * log(y / y0[index1]) / mu1[index1], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho1[index3] <- rho1[index3] + pgamma(q = lambda * log(y1[index3] / y0[index3]) / mu1[index3], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho2[index2] <- rho2[index2] + pgamma(q = lambda * (log(y1[index2] / y0[index2]) / mu1[index2] + (y1[index2]^(1 - r[index2]) - y^(1 - r[index2])) / (alpha[index2] * (1 - r[index2]))), shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) rho2[index3] <- rho2[index3] + pgamma(q = lambda * (log(y1[index3] / y0[index3]) / mu1[index3]), shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) } rho1 <- 1 - rho1 / (m + 1) rho2 <- rho2 / (m + 1) rho <- rho1 + rho2 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoCdf(y, par0) } return(rho[rho != 0]) } .rhoCdf5 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha yb <- param$yb nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau5(y, age, param) for (j in 0:m) { rho[index] <- rho[index] + pgamma(q = log(y1[index] / (y - yb[index])) * lambda / alpha[index], shape = j + 1, rate = 1, lower.tail = FALSE) / factorial(j) } rho[index] <- rho[index] / (m + 1) rho[y > y1] <- 1 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoCdf(y, par0) } return(rho[rho != 0]) } .rhoPdf <- function(y, par) { return(dlnorm(y, meanlog = par[1], sdlog = par[2])) } .rhoPdf1 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau1(y, age, param) deltaTP <- (m + 1) / lambda rho[index] <- pgamma(q = log(y1[index] / y) / alpha[index], shape = m + 1, rate = lambda, lower.tail = FALSE) / (alpha[index] * deltaTP * y) if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoPdf(y, par0) } return(rho[rho != 0]) } .rhoPdf2 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha r <- param$r nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau2(y, age, param) deltaTP <- (m + 1) / lambda rho[index] <- pgamma(q = (y1[index]^(1 - r[index]) - y^(1 - r[index])) / (alpha[index] * (1 - r[index])), shape = m + 1, rate = lambda, lower.tail = FALSE) / (alpha[index] * deltaTP * y^(r[index])) if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoPdf(y, par0) } return(rho[rho != 0]) } .rhoPdf3 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha y0 <- param$y0 mu1 <- param$mu1 nMc <- length(y1) # Rising branch rho1 <- rep(0, nMc) # Decaying branch rho2 <- rep(0, nMc) if (y <= 0) { return(rho1) } index1 <- .tau31(y, age, param) index2 <- .tau32(y, age, param) deltaTP <- (m + 1) / lambda rho1[index1] <- pgamma(q = log(y / y0[index1]) / mu1[index1], shape = m + 1, rate = lambda, lower.tail = FALSE) / (mu1[index1] * deltaTP * y) rho2[index2] <- pgamma(q = log(y1[index2] / y0[index2]) / mu1[index2] + log(y1[index2] / y) / alpha[index2], shape = m + 1, rate = lambda, lower.tail = FALSE) / (alpha[index2] * deltaTP * y) rho <- rho1 + rho2 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoPdf(y, par0) } return(rho[rho != 0]) } .rhoPdf4 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha r <- param$r y0 <- param$y0 mu1 <- param$mu1 nMc <- length(y1) # Rising branch rho1 <- rep(0, nMc) # Decaying branch rho2 <- rep(0, nMc) if (y < 0) { return(rho1) } index1 <- .tau41(y, age, param) index2 <- .tau42(y, age, param) deltaTP <- (m + 1) / lambda rho1[index1] <- pgamma(q = log(y / y0[index1]) / mu1[index1], shape = m + 1, rate = lambda, lower.tail = FALSE) / (mu1[index1] * deltaTP * y) rho2[index2] <- pgamma(q = log(y1[index2] / y0[index2]) / mu1[index2] + (y1[index2]^(1 - r[index2]) - y^(1 - r[index2])) / (alpha[index2] * (1 - r[index2])), shape = m + 1, rate = lambda, lower.tail = FALSE) / (alpha[index2] * deltaTP * y^(r[index2])) rho <- rho1 + rho2 if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoPdf(y, par0) } return(rho[rho != 0]) } .rhoPdf5 <- function(y, age, lambda, m, param, par0) { y1 <- param$y1 alpha <- param$alpha yb <- param$yb nMc <- length(y1) rho <- rep(0, nMc) if (y <= 0) { return(rho) } index <- .tau5(y, age, param) deltaTP <- (m + 1) / lambda rho[index] <- pgamma(q = log(y1[index] / (y - yb[index])) / alpha[index], shape = m + 1, rate = lambda, lower.tail = FALSE) / (alpha[index] * deltaTP * (y - yb[index])) if (!is.na(age)) { sProb <- .surv(age, lambda, m) rho <- rho + sProb * .rhoPdf(y, par0) } return(rho[rho != 0]) } seroincidence/R/data-help.R0000644000176200001440000002357613303571700015263 0ustar liggesusers#' @docType data #' #' @name campylobacterSimLowData #' #' @aliases campylobacterSimLowData campylobacterSimMediumData campylobacterSimHighData #' pertussisSimLowData pertussisSimMediumData pertussisSimHighData #' #' @title #' Simulated Cross-sectional Data #' #' @description #' Simulated cross-sectional population sample of antibody levels data for Campylobacter and #' Pertussis for lambda 0.036/yr (low), 0.021/yr (medium) and 1.15/yr (high). #' #' @usage #' campylobacterSimLowData #' #' @format #' A data frame with 500 observations on the following 2 to 4 variables: #' \describe{ #' \item{Age}{} #' \item{IgG}{} #' \item{IgM}{} #' \item{IgA}{} #' } #' #' @examples #' #' # Show first rows of the data #' head(campylobacterSimLowData) #' #' # Summarize the data #' summary(campylobacterSimLowData) #' NULL #' @docType data #' #' @name campylobacterDelftParams1 #' #' @title #' Campylobacter Delft Response Parameters Data for Model 1 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' campylobacterDelftParams1 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterDelftParams1 #' lapply(campylobacterDelftParams1, head) #' NULL #' @docType data #' #' @name campylobacterDelftParams3 #' #' @title #' Campylobacter Delft Response Parameters Data for Model 3 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' campylobacterDelftParams3 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterDelftParams3 #' lapply(campylobacterDelftParams3, head) #' NULL #' @docType data #' #' @name campylobacterDelftParams4 #' #' @title #' Campylobacter Delft Response Parameters Data for Model 4 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' campylobacterDelftParams4 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterDelftParams4 #' lapply(campylobacterDelftParams4, head) #' NULL #' @docType data #' #' @name campylobacterSSIParams1 #' #' @title #' Campylobacter SSI Response Parameters Data for Model 1 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type #' #' @usage #' campylobacterSSIParams1 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterSSIParams1 #' lapply(campylobacterSSIParams1, head) #' NULL #' @docType data #' #' @name campylobacterSSIParams2 #' #' @title #' Campylobacter SSI Response Parameters Data for Model 2 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type #' #' @usage #' campylobacterSSIParams2 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterSSIParams2 #' lapply(campylobacterSSIParams2, head) #' NULL #' @docType data #' #' @name campylobacterSSIParams4 #' #' @title #' Campylobacter SSI Response Parameters Data for Model 4 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' campylobacterSSIParams4 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in campylobacterSSIParams4 #' lapply(campylobacterSSIParams4, head) #' NULL #' @docType data #' #' @name pertussisIgGPTParams1 #' #' @title #' Pertussis IgG-PT Response Parameters Data for Model 1 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' pertussisIgGPTParams1 #' #' @format #' A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody. #' #' @examples #' #' # Show first rows of every dataframe contained in pertussisIgGPTParams1 #' lapply(pertussisIgGPTParams1, head) #' NULL #' @docType data #' #' @name pertussisIgGPTParams2 #' #' @title #' Pertussis IgG-PT Response Parameters Data for Model 2 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' pertussisIgGPTParams2 #' #' @format #' A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody. #' #' @examples #' #' # Show first rows of every dataframe contained in pertussisIgGPTParams2 #' lapply(pertussisIgGPTParams2, head) #' NULL #' @docType data #' #' @name pertussisIgGPTParams3 #' #' @title #' Pertussis IgG-PT Response Parameters Data for Model 3 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' pertussisIgGPTParams3 #' #' @format #' A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody. #' #' @examples #' #' # Show first rows of every dataframe contained in pertussisIgGPTParams3 #' lapply(pertussisIgGPTParams3, head) #' NULL #' @docType data #' #' @name pertussisIgGPTParams4 #' #' @title #' Pertussis IgG-PT Response Parameters Data for Model 4 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' pertussisIgGPTParams4 #' #' @format #' A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody. #' #' @examples #' #' # Show first rows of every dataframe contained in pertussisIgGPTParams4 #' lapply(pertussisIgGPTParams4, head) #' NULL #' @docType data #' #' @name salmonellaSSIParams1 #' #' @title #' Salmonella SSI Response Parameters Data for Model 1 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' salmonellaSSIParams1 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in salmonellaSSIParams1 #' lapply(salmonellaSSIParams1, head) #' NULL #' @docType data #' #' @name salmonellaSSIParams2 #' #' @title #' Salmonella SSI Response Parameters Data for Model 2 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' salmonellaSSIParams2 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in salmonellaSSIParams2 #' lapply(salmonellaSSIParams2, head) #' NULL #' @docType data #' #' @name salmonellaSSIParams4 #' #' @title #' Salmonella SSI Response Parameters Data for Model 4 #' #' @description #' List of data frames of all longitudinal parameters. Each data frame contains #' Monte Carlo samples for each antibody type. #' #' @usage #' salmonellaSSIParams4 #' #' @format #' A list of three dataframes: #' \describe{ #' \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} #' \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} #' \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} #' } #' #' @examples #' #' # Show first rows of every dataframe contained in salmonellaSSIParams4 #' lapply(salmonellaSSIParams4, head) #' NULL seroincidence/R/summary.seroincidence.R0000644000176200001440000000653513304210153017717 0ustar liggesusers#' @title #' Summary Method for Seroincidence Object #' #' @description #' Calculate seroincidence from output of the seroincidence calculator #' \code{\link{estimateSeroincidence}}. #' #' @param object A dataframe containing output of function \code{\link{estimateSeroincidence}}. #' @param ... Additional arguments affecting the summary produced. #' @param quantiles A vector of length 2 specifying quantiles for lower (first element) and upper #' (second element) bounds of \code{lambda}. Default = \code{c(0.025, 0.975)}. #' @param showDeviance Logical flag (\code{FALSE}/\code{TRUE}) for reporting deviance #' (-2*log(likelihood) at estimated seroincidence. Default = \code{TRUE}. #' @param showConvergence Logical flag (\code{FALSE}/\code{TRUE}) for reporting convergence (see #' help for \code{\link{optim}} for details). Default = \code{TRUE}. #' #' @return #' A list with the following items: #' \describe{ #' \item{\code{Results}}{Dataframe with maximum likelihood estimate of \code{lambda} (the #' seroincidence) (column \code{Lambda}) and corresponding lower (\code{Lambda.lwr}) and upper #' (\code{Lambda.upr} bounds.\cr #' Optionally \code{Deviance} (Negative log likelihood (NLL) at estimated (maximum likelihood) #' \code{lambda}) and \code{Covergence} (Convergence indicator returned by \code{\link{optim}}. #' Value of 0 indicates convergence) columns are included.} #' \item{\code{Antibodies}}{Character vector with names of input antibodies used in #' \code{\link{estimateSeroincidence}}.} #' \item{\code{Strata}}{Character with names of strata used in \code{\link{estimateSeroincidence}}.} #' \item{\code{CensorLimits}}{List of cutoffs for each of the antibodies used in #' \code{\link{estimateSeroincidence}}.} #' } #' #' @examples #' #' \dontrun{ #' # estimate seroincidence #' seroincidence <- estimateSeroincidence(...) #' #' # calculate summary statistics for the seroincidence object #' seroincidenceSummary <- summary(seroincidence) #' } #' #' @export summary.seroincidence <- function(object, ..., quantiles = c(0.025, 0.975), showDeviance = TRUE, showConvergence = TRUE) { # R CMD check warnings workaround hessian <- NULL value <- NULL convergence <- NULL if (length(quantiles) != 2 || any(quantiles < 0) || any(quantiles > 1)) { stop("Incorrectly specified quantiles") } if (quantiles[1] > quantiles[2]) { stop("Quantile for upper bound of incidence estimate cannot be less than the lower bound.") } fits <- object[["Fits"]] results <- as.data.frame(t(sapply(fits, FUN = function(elem) { with(elem, c( Lambda.est = 365.25 * exp(par + qnorm(0.5) * sqrt(1 / hessian)), Lambda.lwr = 365.25 * exp(par + qnorm(quantiles[1]) * sqrt(1 / hessian)), Lambda.upr = 365.25 * exp(par + qnorm(quantiles[2]) * sqrt(1 / hessian)), Deviance = 2 * value, Convergence = convergence)) }))) results$Stratum <- rownames(results) rownames(results) <- NULL if (!showDeviance) { results$Deviance <- NULL } if (!showConvergence) { results$Convergence <- NULL } output <- list(Results = results, Antibodies = object[["Antibodies"]], Strata = object[["Strata"]], CensorLimits = object[["CensorLimits"]], Quantiles = quantiles) class(output) <- c("summary.seroincidence", "list") return(output) } seroincidence/R/surv.R0000644000176200001440000000013413304777066014422 0ustar liggesusers.surv <- function(a, lambda, m) { return(pgamma(lambda * a, m + 1, lower.tail = FALSE)) } seroincidence/R/optNll.R0000644000176200001440000000145113304777066014676 0ustar liggesusers.optNll <- function(stratumData, antibodies, params, censorLimits, ivc = FALSE, m, par0, start) { # Any column but "Stratum" incidence can not be calculated if there are zero observations. if (nrow(stratumData) == 0) { return(NULL) } # First, check if we find numeric results... res <- .nll(stratumData, antibodies, params, censorLimits, ivc, m, par0, start) if (is.na(res)) { return(NULL) } # Estimate log.lambda fit <- stats::optim(par = start, fn = .nll, stratumData = stratumData, antibodies = antibodies, params = params, censorLimits = censorLimits, ivc = ivc, m = 0, par0 = par0, method = "L-BFGS-B", lower = -13, upper = 0, hessian = TRUE, control = list(fnscale = 1)) return(fit) } seroincidence/R/deltaFunc.R0000644000176200001440000000043013304777066015327 0ustar liggesusers.deltaFunc <- function(yDat, lambda, m, param, fun, par0) { deltaRho <- fun(y = yDat[2], age = yDat[3], lambda = lambda, m = m, param = param, par0 = par0) - fun(y = yDat[1], age = yDat[3], lambda = lambda, m = m, param = param, par0 = par0) return(mean(deltaRho)) } seroincidence/vignettes/0000755000176200001440000000000013305523607015100 5ustar liggesusersseroincidence/vignettes/installation.Rmd0000644000176200001440000001404113305507007020241 0ustar liggesusers--- title: "Seroincidence package installation manual" author: "European Centre for Disease Prevention and Control (ECDC)" date: "`r Sys.Date()`" output: pdf_document: toc: yes header-includes: - \setkeys{Gin}{height=2.8in, keepaspectratio} \DeclareUnicodeCharacter{2010}{-} vignette: > %\VignetteIndexEntry{Seroincidence package installation manual} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} # Grab package version and date from DESCRIPTION file. pkgVersion <- packageDescription("seroincidence")$Version pkgDate <- packageDescription("seroincidence")$Date pkgBaseFileName <- paste("seroincidence", pkgVersion, sep = "_") pkgUrl <- gsub("\n", "", packageDescription("seroincidence")$URL) pkgPath <- "http://ecdc.europa.eu/en/data-tools/seroincidence-calculator-tool/Documents" library("knitr") ``` \newpage # 1. Introduction Package **seroincidence** is written in programming language R and end user must have access to a working installation of R engine. This document describes the most common setup with R installed locally on the user's computer. The screenshots refer to the classical R interface, but the package can also be opened in other Graphical User Interfaces fo R like e.g. [RStudio](http://www.rstudio.com/products/RStudio/). # 2. Installation steps R is a free software and can be downloaded from [http://cran.r-project.org/](http://cran.r-project.org/). Latest version as of writing this document is **R 3.5.0**. Once the appropriate, operating system dependent, version is downloaded, install it on your computer following the standard procedure applicable to the operating system. For Windows the file to be downloaded is the so-called *base* distribution: [http://cran.r-project.org/bin/windows/base/](http://cran.r-project.org/bin/windows/base/). ## 2.1. Installing R Start the R installer and follow the presented steps: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup1.png") ``` It is advised to have R installed in folder that does not contain spaces, therefore please adjust the destination location accordingly: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup2.png") ``` The **seroincidence** package is compatible with both the 32-bit and the 64-bit version of R. Choose the preferred platform (or both). If unsure install the 32-bit version only, however on compatible platforms the 64-bit version may provide better performance: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup3.png") ``` It is advised to select *Registry entries* in the next step for best experience: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/setup4.png") ``` R interpreter, when installed on Windows, can be invoked from the start menu folder named **R**. Start the preferred version of R (if both the 32-bit: *R i386* and the 64-bit: *x64* are installed). Graphical user interface for R interpreter will start in a new window: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui1.png") ``` ## 2.2. Installing *seroincidence* package Since this is a new installation of R, the **seroincidence** package must be installed before first use. The package can be installed either through a menu option in the graphical user interface (GUI) or with a command executed in the R console. Both options are presented: ### 2.2.1. Package installation from the graphical user interface Download the seroincidence calculator package from ECDC website: [`r pkgUrl`](`r pkgUrl`). Two versions of the package are made available: * binary package (seroincidence_[version].zip) - Microsoft Windows compatible * Source package (seroincidence_[version].tar.gz) - cross-platform compatible (MS Windows, Linux, MacOS) If your operating system is Windows then it is best to download the Windows binary package. Go to menu *Packages* and select command *Install package(s) from local files...*: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui2.png") ``` Select the package file and click "Open": ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui3.png") ``` Post-installation message should appear: ```{r echo=FALSE, fig.pos="!h", fig.align='center'} include_graphics("fig/RGui4.png") ``` The package is now installed in R. ### 2.2.2. Package installation from R console Alternatively, installation of the package can also be performed by executing one of the following commands in the *R console*: ```{r, include=FALSE, tidy=FALSE} chunkTemplate <- "```{r, eval = FALSE} # OPTION A # Install Windows binary package \"seroincidence\" directly from internet ECDC website: install.packages( pkgs = \"{{pkgPath}}/ {{pkgBaseFileName}}.zip\", repos = NULL, type = \"win.binary\") # OPTION B # Install source package directly from internet CRAN repository: install.packages(\"seroincidence\") # OPTION C # Install Windows binary package from a local file: # install.packages(\"[PATH/TO/FILE/]seroincidence_[version].zip\", # repos = NULL, type = \"win.binary\") # For instance: install.packages(pkgs = \"C:/{{pkgBaseFileName}}.zip\", repos = NULL, type = \"win.binary\") # OPTION D # Install source package from a local file: install.packages(pkgs = \"C:/{{pkgBaseFileName}}.tar.gz\", repos = NULL, type = \"source\") ```" chunkSource <- knit_expand(text = chunkTemplate, pkgBaseFileName = pkgBaseFileName) ``` `r knit(text = chunkSource)` # 3. Post-installation Successful installation can be confirmed by loading the package into the workspace and exploring help files and manuals distributed with the package: ```{r, eval=FALSE} # Load package "seroincidence". library(seroincidence) # Show R help for the package. ?seroincidence # Show tutorial for the package. vignette(topic = "tutorial", package = "seroincidence") ``` Additionally, most package details can be found when executing the following commands: ```{r} # Show description. packageDescription("seroincidence") # Show citation. citation("seroincidence") ``` seroincidence/vignettes/fig/0000755000176200001440000000000013305523457015650 5ustar liggesusersseroincidence/vignettes/fig/response.pdf0000644000176200001440000003642112325733440020203 0ustar liggesusers%PDF-1.4 %쏢 6 0 obj <> stream xX]W*Ds8Ha)lW1 1֐Ԟ +c➳pf8/cHQBWjۿW CcoﯬDχKRUbnW_JH JNZ -Yb@AB9QlHCS8zا)9jسјeqj,жi&8{iuQ4ΎfZ ]⛞k:XFIXu'IC%jgw@(KH1"#.!CL>KAU3dPrۧ93.Wj-iJ"S`P( 3&sD 1k *<=:[1ĉVX8[-$ppF)C!30Ҍx(I,*APc#8LP(7C+!Q!2CTnjVEZ_\Xe{NZ  [,d R!'R߈&">XEQ lUC$ab-8*-=/ XvlZiWYT+lo&S7qH7vH LG;GlsXcf1`0r ad,gjˀ}uɩE2z.D"@v}Y6 &W#{Ɋ |PDD%)[=,G9lu(B$I1V1mUוPMrq.9)+vZ$n_!y` AfD=Nfzd9X2 l+<0FA)V [ѣ aVb,;"BEjf$|C\E.ZN  ()#82U d;J-`9=L)D$}('E U$ AD[ENfϐ+UXE 5E;upavt8ϐ`]j(+Yu`a,p>\ZZZpcY?d&&ZP"gMeU,M ӬZAN ^YMDlEPHY6Nvj-rԘBv.V#Vu Xe sN.W6 B$WP}t-jbi}uܙ`@^;,]K`.}Gc ";B慬X0$UTϺfV7lAĂ3yiK. {;l\1d/Bp~DBi9MIfLB8؉`XH3WYн:qAcRFMrDi:6Mb">C>3;@wA?` WZsSAICRq*E_͸uc,Jͦͽ%{/|?>Mvmg7\ l@uaeJcGC9)肫6q@(sApr.tܜs7 >ﮉ" oAnDt̮{76An:E 7z.%/sJtܒքx0g#:E~HڈӨa:Iqql9q^ACFMIqwCFn*4_oq8CFF_t[1de/ $tf+IQGaIqe!i#n7vzz}$%3gְ%yk]:?K?`~Q|,H/m5$E;4:p}ׯ?^#W)@=^Vxa[}5rǗv|קs||>89[sq>y96I99yΞ?%Yfc9 FYvAnNWQqb8FnNåpy. ӛh;-i۪t(99|8NQʾ|v::Pn.݂8 ܴCF'!g#yEi'oBNL]O~h{8|,ۀg{ |XYz݈40q{g~i|n5S\"1FvʘfqChR1:HkV'dW^M"H"| uvo/s71jq_.f/߿w[[ܘ2gD9<6Z~tl@>ޟendstream endobj 7 0 obj 2259 endobj 5 0 obj <> /Contents 6 0 R >> endobj 3 0 obj << /Type /Pages /Kids [ 5 0 R ] /Count 1 >> endobj 1 0 obj <> endobj 8 0 obj <>endobj 4 0 obj <>stream x{ٮF}j`0?46wA".)"R6H G*rnq̌Ȉ"k^dz%i|]#TX$ǐX;>+ǿ}~XNZWa}Q 2߿gU;[+ H['HPA! }7ķ&b}>oطBModPqkp".CMyۼ{F<}$W}fԌ>ev- AӯLN{pjm/IU5w˛_p(ƿA1(>`F?OzuԄy5~OE2TS]8udlᚼՀO4S%~AY!G}jڰ[;}jڸ#D0U^NfXAb #ĩ0QVu`@b2=U`ܠ8xHN=ipL+V~11~d3wPm` xWs?U8!sLlϞO~ jLeG%2#@#>7#e]ZD)xY*qI zJ*1 pLj hjTX KQ8FIS˱2]`:9FS燖E9xS,d'ނIsð~|D6|= =d.hօ4FM'~YT9iEcKr. ˓`5'4idȼyBriM_  `.FpdADo:ˎ܁=ZsSˤ$FWE4wOu9>NɥYh9{=`%cNyO" /qF}K'Ax?UNYŁv#եH@=w\u/u7_ y+sمauߓ4 qoq|31bhD[Sړ`@0:$7ŚIMZ/>?U%tA6*f0)I^:@ϓMcK4@:rQr륭EX=eg.zDTN$ڋ+T^]fgOwyIV޲q:(&Kqx/77A 䜜R:&~zWװSTCx\ՃzW3C>H$"tg FA-j!6T%]諽 ;Qխmb:dxiwQ>>V5Gbִ6|A ;)w?{|}#\sEU_b{LДYI{Qy<ÐjQMѨFlv hr8tq}QVVm"JVm$B29|UşTY'\ɗsFB'jKI\be7IJXL,ֻ8/4x>=m#JDCI#1 {d%sI0Qau܊a2 ۈގhCOGwvJ􌄭2|;y}ݞТe ׉6~EXRS֡U׈HY|"R;$7KxtE/;tp  |BKkE @21݉Y;{Y"\8t$(n|} v\{u`g{5+ƿO)IQdhAn{؋IǩZ#a3bfy/{-꠆G`kNChys z`IOۍ|XN}[ށZcZ'Я0t \axrkҠg$<꾋|~g+ <2uQ:"oBLS'(zrgpG=rr98w'qcMpVwWKw]/xR"g\o !_&Eǔ{ KjK& tA^kh|9yڨ}PZ 3 w/EFc Н4͇2# sR עK8sD\Zl#}ʉ.v2#fvY 2!p7l2o=^a=L<`Fpyi-tPث4gy:v)n ^}> F#>-[6i6OVp|re'l.eZ8NjiTzC<ƵQ'f4`u y }7- E.zpDյ; vPO>)oŀW6M|4AgnQ"aW"&c>} r-$VVU7@eM7"zF;kʥ8_]Xt>U`4)j^V: )߮ǃ]2ݝ o8@9asn< ,cDQYʮlߧ _eGYp@SipC5zLhM0?b[$_)w/}RLB,FJhC -&Ҁ_~3\꒗w^pCcOj1_Vt/EJnpmI>#l ݀:76GԹcZTXw٬oal\F cWY(Ng8muϚrٳ6YXڰq1rǭo\ )`(s!fQNrHE"[\Nk-Sf{WM[ȿ^ኝmEDiZqXK,<^ 3/ rZ &.Yr"$:ݥ:>LtuݍuۮE~[|\ڮ;/u93?g7´^ݼSO^6|}gsWmR 𚹵$g1iѪN4|QX5Wϟ/y?{$kAv R !Prw!jLXx7zO~nh$EH>Q5MuТ_a%Un#7f>QQJǃ" +lBXBxچs ]w`L=̐G$5[wh7*'* p+ ubmQvQS;rvm=epn0,5ã_e̡yLp4u ʇ.7U:3ix%gH)N1:כAm."L*lzwWe#̅B"F;g5E:dž\I,@}f]:eAT)Izݏ *ideGߑlF3(b hߦUsFaU@ 0}<;.8Tz~N+=tdW1mWj u)c+FtGFWH-6vAuqTIrY8A>9c@BxkǍ·5Bs GI+f :Ǔ Xع%NDz,ҏԖt5Do+zSxu}}Ȃ}E9N kܳ:O2=mekyS}M-;Ks!xoRy' hhc^Qo,{F0Cs2vCf6kYB ;2};;9z7RTt 'H.o@dso/:9Lcp#LdCH0HZ];[o-.W\ۆĶB_yi3ս_aB2&ZD8ǒ2پ܌ Q5J&ebKQ$t7w'ΓgȾ5ցmNMCl6e$6 y/qM,߽ާlPn >nF]ayRl]F]6 ի-7ܣR"-arI"vdJNC-_IbocOaZez7vL ]`Ƞ.,JRTO:{GlWo`;. 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S:{㮳dӗ1U̡w^tנ/\ +[|{vb:~&WnٟMڽy soow>ֿvb~˵on|Hğ˔i;gߤ٘?ok)XMzu9Gb\qm(v@4CWhmmуߝ E:𥣘u;̈(u[sڼ; uޮL9ǶOoK_8y ]hD 38zn Iw;Jb|c-e`nwo'Y+f@إ81hFrb+lAM_oO0~(_:yfu#~>0Zc˝?-׾Z]$J%PVsjr.}_Hf),_V/=+Jdk D3tg:z^Q pw*D:ʼ9VI_dXgмWmkH)ƯdR|w;OOG|bNCmv\|G>WQ k.LL?2匟4ȷe;~zqq߀|IƗ|ϓfJoF>Ӟ;l>OwTykU\NґW~o6Wo't'0Xl slLO_}=}ִWp?Wu"S^!Zr[u|ts]" \|r>տt~37?ğ!ilu90F1Ť /NΊW\Rmw,vut[2ځ H34לW׏`̦6X<ؤ!0 V{ d"Nxl2y5ϻ:JO:}K3eji}7OJr7}[yJQo_iRuԤWԳQPaZޜ)akLGCS7~:9}rgID3t:ҷzwغN ,jG1n6 ]bz;8Ǿ"ehwR78>hT[hT?R-|N2+`AhT?RafJX+ՖAUUվ|mx0~5+vw\]PR[ ,?Е>whߩ"6E,̍fh Ə 0 F3scX#BSqBiǜv@MhsF/| 43盽afD%OXsʙ>`!hfn0~ A3scX#Baf4#7V?-B!!BaB!N0~!B'D[5~!B'IF[3~.B!M!B-MJZz7~(B!qܞIK?B#ֶVh[B!ZH~:Z[3~"@B!IOKKw!B0~!B VlC!ZbfC!:!!Be&B!t< B!tC!:!!BaB!N0~!B'DQ''B!jB!TB!t|C!:!!BaB!N0~!B'DC!B]WT?ƙkIENDB`seroincidence/vignettes/methodology.Rmd0000644000176200001440000004225513305523173020104 0ustar liggesusers--- title: "Seroincidence package methodology" author: "European Centre for Disease Prevention and Control (ECDC)" date: '`r Sys.Date()`' output: pdf_document: toc: yes header-includes: - \usepackage{subfigure} \DeclareUnicodeCharacter{2010}{-} references: - id: teunis_etal12_biomarker DOI: 10.1002/sim.5322 author: - family: Teunis given: P. F. M. - family: van Eijkeren given: J. C. - family: Ang given: C. W. - family: van Duynhoven given: Y. T. - family: Simonsen given: J. B. - family: Strid given: M. A. - family: van Pelt given: W. container-title: Statistics in Medicine issue: 20 issued: month: 9 year: 2012 page: 2240-2248 title: 'Biomarker dynamics: estimating infection rates from serological data' type: article-journal volume: 31 - id: degraaf_etal14wh author: - family: de Graaf given: W. F. - family: Kretzschmar given: M. E. E. - family: Teunis given: P. F. M. - family: Diekmann given: O. container-title: Epidemics DOI: 10.1016/j.epidem.2014.08.002 issued: month: 12 year: 2014 page: 1-7 title: 'A two-phase within-host model for immune response and its application to serological profiles of pertussis' type: article-journal volume: 9 - id: teunis_etal16withinhost author: - family: Teunis given: P. F. M. - family: van Eijkeren given: J. C. - family: de Graaf given: W. F. - family: Bonačić Marinović given: A. - family: Kretzschmar given: M. E. E. container-title: Epidemics DOI: 10.1016/j.epidem.2016.04.001 issued: month: 9 year: 2016 page: 33-39 title: 'Linking the seroresponse to infection to within-host heterogeneity in antibody production' type: article-journal volume: 16 - id: satten_etal04 author: - family: Satten given: G. A. - family: Kong given: F. - family: Wright given: D. J. - family: Glynn given: S. A. - family: Schreiber given: G. B. container-title: Biostatistics DOI: 10.1093/biostatistics/5.1.145 issued: month: 1 year: 2004 page: 145-151 title: 'How special is a ‘special’ interval: modeling departure from length‐biased sampling in renewal processes' type: article-journal volume: 5 issue: 1 - id: zelen04 author: - family: Zelen given: M. container-title: Lifetime Data Analysis issued: month: 12 year: 2004 page: 325-334 title: 'Forward and backward recurrence times and length biased sampling: age specific models' type: article-journal volume: 10 issue: 4 - id: degreeff_etal12 author: - family: de Greeff given: S. C. - family: Teunis given: P. F. M. - family: de Melker given: H. E. - family: Mooi given: F. R. - family: Notermans given: D. W. - family: Elvers given: B. - family: Schellekens given: J. F. P. container-title: Clinical and Vaccine Immunology DOI: 10.1128/CVI.00229-12 issued: month: 9 year: 2012 page: 1452-1456 title: 'Two-Component Cluster Analysis of a Large Serodiagnostic Database for Specificity of Increases of IgG Antibodies against Pertussis Toxin in Paired Serum Samples and of Absolute Values in Single Serum Samples' type: article-journal volume: 19 issue: 9 fontsize: 11pt vignette: > %\VignetteIndexEntry{Seroincidence package methodology} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- \newpage # Introduction The revised seroincidence calculator package provides three refinements to the method for calculating seroincidence published earlier [@teunis_etal12_biomarker] and implemented in R package **seroincidence**, versions 1.x: (1) inclusion of infection episode with rising antibody levels, (2) non--exponential decay of serum antibodies after infection, and (3) age--dependent correction for subjects who have never seroconverted. It is important to note that, although the implemented methods use a specific parametric model, as proposed in [@degraaf_etal14wh] and augmented in [@teunis_etal16withinhost], the methods used to calculate the likelihood function allow seroresponses of arbitrary shape. # 1. A simple model for the seroresponse The current version of the seroincidence package uses the model of [@teunis_etal16withinhost] for the shape of the seroresponse: $$ \begin{array}{l@{\qquad}l} \text{Infection/colonization episode} & \text{Waning immunity episode}\\ b^{\prime}(t) = \mu_{0}b(t) - cy(t) & b(t) = 0 \\ y^{\prime}(t) = \mu y(t) & y^{\prime}(t) = -\nu y(t)^r \\ \end{array} $$ With baseline antibody concentration $y(0) = y_{0}$ and initial pathogen concentration $b(0) = b_{0}$. The serum antibody response $y(t)$ can be written as $$ y(t) = y_{+}(t) + y_{-}(t) $$ where \begin{align*} y_{+}(t) & = y_{0}\text{e}^{\mu t}[0\le t 1$, log concentrations decrease rapidly after infection has terminated, but decay then slows down and low antibody concentrations are maintained for a long period. When $r$ approaches 1, exponential decay is restored. # 2. Backward recurrence time Considering the (fundamental) uniform distribution $u_{f}$ of sampling within a given interval, the interval length distribution $p(\Delta t)$ and the distribution of (cross--sectionally) sampled interval length [@teunis_etal12_biomarker] $$ q(\Delta t) = \frac{p(\Delta t)\cdot\Delta t}{\overline{\Delta t_{p}}} $$ the joint distribution of backward recurrence time and cross--sectional interval length is the product $u_{f}\cdot q$ because these probabilities are independent. The distribution of backward recurrence time is the marginal distribution \begin{align*} u(\tau) & = \int_{\Delta t=0}^{\infty} u_{f}(\tau;\Delta t)\cdot q(\Delta t)\text{d}\Delta t\\ & = \int_{0}^{\infty}\frac{[0\le\tau\le\Delta t]}{\Delta t}\cdot \frac{p(\Delta t)\cdot \Delta t}{\overline{\Delta t_{p}}}\text{d}\Delta t\\ & = \frac{1}{\overline{\Delta t_{p}}}\int_{\tau}^{\infty}p(\Delta t)\text{d}\Delta t \end{align*} # 3. Incidence of seroconversions To calculate the incidence of seroconversions, as in [@teunis_etal12_biomarker], the distribution $p(\Delta t)$ of intervals $\Delta t$ between seroconversions, is important. Assuming any subject is sampled completely at random during their intervals between seroconversions, and accounting for interval length bias [@satten_etal04; @zelen04], the distribution of backward recurrence times $\tau$ can be written as [@teunis_etal12_biomarker] $$ u(\tau) = \frac{1}{\overline{\Delta t}} \int_{\tau=0}^{\infty}p(\Delta t)\text{d}\Delta t = \frac{1-P(\Delta t)}{\overline{\Delta t}} $$ where $\overline{\Delta t}$ is the $p$--distribution expected value of $\Delta t$. This density is employed to estimate seroconversion rates. The antibody concentration $y$ is the observable quantity, and we need to express the probability (density) of observed $y$ in terms of the density of backward recurrence time. First, the backward recurrence time can $\tau$ be expressed as a function of the serum antibody concentration $y$ $$ \tau(y) = \tau_{+}(y) + \tau_{-}(y) $$ where \begin{align*} \tau_{+}(y) & = \displaystyle{\frac{1}{\mu}} \log\left(\displaystyle{\frac{y_{+}}{y_{0}}}\right) [0\le \tau %\VignetteIndexEntry{Seroincidence package tutorial} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} pkgUrl <- gsub("\n", "", packageDescription("seroincidence")$URL) ``` \newpage # 1. Introduction Antibody levels measured in a (cross–sectional) population sample can be translated into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. In simple terms: the presence of many high antibody concentrations indicates that many subjects likely experienced infection recently, while mostly low concentrations indicate a low frequency of infections in the sampled population. More information about ELISA methods can be found on [ECDC web site](`r pkgUrl`). In order to thus interpret the measured cross-sectional antibody concentrations, characteristics of the time course of the serum antibody response must be known. For any antibody detected in the cross–sectional sample, a quantitative description of its dynamics following infection (seroconversion to an elevated concentration, followed by a gradual decrease) must be available. In published studies, this information on the time course of the serum antibody response has been obtained from follow–up data in subjects who had a symptomatic episode following infection. The onset of symptoms thus provided a proxy for the time that infection occurred. Care must be taken that longitudinal and cross–sectional measurements of antibody concentrations are calibrated on the same scale (or, preferably, expressed in identical units). The time course of the serum antibody response to infection is assumed generic: anyone infected by the same pathogen is expected to produce a response similar to those seen in the symptomatic cohort used for the follow–up study. Thus, the strategy is to set up a longitudinal model from a follow–up study once, and use the thus obtained information to analyze many different cross–sectional data sets. Note that it must be assumed that such variation in the time course of antibody concentrations among individuals as observed in the longitudinal cohort is the same as in the population where the cross-sectional sample was taken, where this variation cannot be observed. Analysis of longitudinal data and estimation of the required parameters is separated from the estimation of seroincidences, because (1) there are few longitudinal data sets available and they are difficult (and expensive) to obtain, (2) such longitudinal models may be considered *generic*, presumably describing a physiological phenomenon that is similiar in any infected individual, and (3) setting up and running the longitudinal model requires additional skills, not necessary for use of the sero–incidence calculator script # 2. The seroincidence estimator Package **seroincidence** was designed to calculate incidence of seroconversion, by using the longitudinal seroresponse characteristics. The distribution of serum antibody concentrations in a cross–sectional population sample is calculated, as a function of the (longitudinal) seroresponse and the frequency of seroconversion (or seroincidence). Given the seroresponse, this (marginal) distribution of antibody concentrations can be fitted to the cross-sectional data, by adjusting the seroconversion frequency, thus providing a means to estimate the seroconversion frequency. ## 2.1 Time course of serum antibodies The seroresponse, the time course of serum antibodies following seroconversion (infection) is described by means of a set of parameters describing it. These parameters may include: a) baseline antibody concentration, b) time to reach peak antibody concentration, c) magnitude of the peak concentration, and d) antibody decay parameters describing the time course (shape and rate) of antibody decay. A model description that is used for the serocalculator is described in [@2; @3]. An alternative model, simplified but with improved interpretation of the underlying biological mechanisms, is given in [@1] and further improved in [@4]. The current model assumes that upon exposure to an initial inoculum, pathogen concentrations increase exponentially. Presence of pathogens (antigen presented to the immune system) signals an increase in antibody production, resulting in exponentially increasing serum antibody concentrations. Increased activity of the immune system, as signalled by circulating antibodies, causes inactivation or die–off of pathogens, with a rate proportional to the serum antibody concentration. Ultimately, when all pathogens are removed, infection is over and the promotion of antibody production stops. Then the decay phase starts, and serum antibody concentrations decrease. Antibody decay in the serum compartment may start fast and slow down later, resulting in non–exponential decay. In [@4] this is modelled using a shape parameter, allowing gradual adjustment between exponential (log–linear) and strongly non–exponential decay. ## 2.2 Heterogenity The five parameters describing the seroresponse (in round brackets names of corresponding parameters used in the package, see [section 3.2.2](#longParams) for details): baseline antibody concentration (`y0` and `yb`), time to peak (`t1`), peak antibody concentration (`y1`), decay rate (`alpha`) and shape factor of the decay curve (`r`) are not fixed numbers. In a population of subjects, individuals each have their own seroresponse, different from those of other subjects. Therefore, these parameters are provided as a (joint) distribution, describing their variation among individuals in the sampled population. Of course, such a distribution depends on the pathogen, the detected antibody, and even the detection assay. Estimates for these seroresponse parameters may be obtained by fitting the model to longitudinal data. Typically, such data are collected in patients with confirmed infection, where the time of infection is detected by appearance of symptoms. Ideally, blood samples are taken at several times post infection, up to a period long enough to reliably estimate the shape of the serum antibody decay curve. A Bayesian hierarchical framework allows for individual variation in seroresponses, so that one obtains the (posterior) joint distribution of the parameters as a (Markov chain) Monte Carlo sample, of all relevant parameters [@4]. Note that, due to the limited number of iterations in the Monte Carlo sample, the generated incidence estimates will show minor variations: if the same calculation is run twice, the outcomes may differ slightly. If this variation should be smaller, the size of the Monte Carlo sample may be increased. This however will slow down the calculations. ## 2.3 Incidence estimation The longitudinal seroresponses are considered generic: they represent the time course of (specific) human serum antibodies against a (specific) pathogen. Therefore, with any cross–sectional sample of the same antibodies in a human population, an incidence estimate can be calculated. Given the longitudinal response characteristics, **seroincidence** R package provide a rapid and computationally simple method for calculating seroconversion rates, as published in [@3]. The methods on which the seroincidence calculator is based were developed with publicly funded research. All procedures have been published and are open to the general public, including the core script on which the seroincidence calculator is based. To make the functionalities provided as broadly available as possible, R was chosen as the computing platform, because it is free and open source, and runs on any modern computer operating system. ## 2.4 Model variants The package contains longitudinal models for seroincidence calculations. Four model variants are possible, depending on whether seroconversion is instantaneous ($t_{1} = 0$) or not ($t_{1} > 0$), and whether decay is exponential ($r = 1$) or proceeds as a power function ($r > 1$). Power function decay allows for rapid inital decay followed by a sustained period of very slow decay [@4]. Available model variants are described in Table 1. \begin{table}[!h] \centering \caption{Model variants} \vspace{0.3cm} \begin{footnotesize} \begin{tabular}{ccc} & Time to & Decay\\ Model & Seroconversion ($t_{1}$) & parameter ($r$)\\ 1 & 0 & 1\\ 2 & 0 & $> 1$\\ 3 & $> 0$ & 1\\ 4 & $> 0$ & $> 1$\\ \end{tabular} \begin{tabular}{lllcccc} & & & \multicolumn{4}{c}{Model}\\ Pathogen & Antibody & Units & 1 & 2 & 3 & 4\\ \hline {\em Campylobacter jejuni} & IgG & ELISA (Delft) & * & & * & * \\ & IgM & ELISA (Delft) & * & & * & * \\ & IgA & ELISA (Delft) & * & & * & * \\ & IgG & ELISA (SSI) & * & * & & * \\ & IgM & ELISA (SSI) & * & * & & * \\ & IgA & ELISA (SSI) & * & * & & * \\ \hline {\em Salmonella} & IgG & mixed ELISA (SSI) & * & * & & * \\ & IgM & mixed ELISA (SSI) & * & * & & * \\ & IgA & mixed ELISA (SSI) & * & * & & * \\ \hline {\em Bordetella pertussis} & IgG-PT & IU & * & * & * & * \\ \hline \end{tabular} \end{footnotesize} \end{table} # 3. How to use *seroincidence* package This section provides step-by-step directions on the usage of the *seroincidence* package. ## 3.1. Loading the package Functionality of the *seroincidence* package is made available to the end user only once the library is loaded into the current workspace. Assuming the package is installed already (covered in [installation.pdf](installation.pdf)) loading is achieved by running the following command in the R console (bear in mind that the text after character `#` is only a comment): ```{r} # Load package "seroincidence" library(seroincidence) ``` At this moment all functions required to run the seroincidence calculation are made available. It can be checked by running: ```{r, eval=FALSE} # List all objects (functions and data) exposed by package "seroincidence". ls("package:seroincidence") ``` Here is the resulting output: ```{r, echo=FALSE} ls("package:seroincidence") ``` We briefly describe the most important objects and functions: a) `[DISEASE]Params[MODEL_TYPE]`: Monte Carlo sample of longitudinal response parameters per antibody for various diseases: Campylobacter, Pertussis, Salmonella. Object class: `list`. b) `[DISEASE]Sim[Low|Medium|High]Data`: Example simulated antibody levels data measured in a cross-sectional population for three values of lambda (incidence): 0.036 ("Low"), 0.21 ("Medium") and 1.15 ("High") (1/yr). Object class: `data.frame`. c) `getAdditionalData`: Utility function for downloading additional longitudinal response parameters from an online repository. Files available for download are `coxiellaIFAParams4.zip` and `yersiniaSSIParams4.zip`. Object class: `function`. d) `estimateSeroincidence`: Main function of the package. Estimates seroincidence based on supplied cross-section antibody levels data and longitudinal response parameters. Object class: `function`. ## 3.2. Specifying input data There are two sets of inputs to the serology calculator that must always be specified: a) Simulated antibody levels measured in cross-sectional population sample (see `campylobacterSimLowData`, `campylobacterSimMediumData`, etc. above). b) Longitudinal response characteristic as set of parameters `(y1, alpha, yb, r, y0, mu1, t1)` (see `campylobacterDelftParams1`, `campylobacterSSIParams2`, etc. above). We start with loading antibody levels measured in cross-sectional population sample. ### 3.2.1. Specifying cross-sectional antibody levels data The user has a few options of providing this data to the calculator: **i) Using supplied sample data** Data set `campylobacterSimMediumData` provides an example of a cross-sectional antibody levels data for Campylobacter. It is loaded into the workspace as soon as the package is loaded, therefore it can be referenced right away. Here is a small exempt from this data set: ```{r} # Show three first rows of "campylobacterSimMediumData" data.frame. head(campylobacterSimMediumData, 3) ``` Let us create the serology data `serologyData` based on this data set: ```{r} # Assign data.frame "campylobacterDelftData" to object named "serologyData". serologyData <- with(campylobacterSimMediumData, data.frame( Age = Age, IgG = IgG, IgM = IgM, IgA = IgA, AgeCat = cut(Age, 15, labels = FALSE))) # Print a few first observations. head(serologyData) ``` You can view the data also in a tabular form: ```{r, eval=FALSE} View(serologyData) ``` We shall pass this object later to the calculator. Object `serologyData` must contain at least one column named `IgG`, `IgM`, or `IgA`. Additionally, column `Age` is used in the calculations if it is present. Otherwise, it is created on-the-fly and initialized to `NA` (not available). Column `Age`, if supplied, is assumed to represent age in days. Please, note that the cross-sectional data set can include extra columns allowing performing the seroincidence calculations stratified per factors available in those data. In the example above column `AgeCat` can be used as a *stratum* variable. This particular variable is created by mapping the age in days (column `Age`) into 15 categories, category 1 grouping the youngest subjects and category 15 grouping the oldest subjects. **ii) Loading from external files** The user can load her/his own data into an R session. Details on loading specific file types can be found in online R manual on [R Data Import/Export](http://cran.r-project.org/doc/manuals/r-release/R-data.html). It is important that the input data is in a tabular form with each column containing levels measured for a single antibody type. Column name should indicate name of the measured antibody. For instance, a comma separated file with the following content: ``` IgG, IgM, IgA 5.337300, 0.4414653, 0.3002395 3.534118, 0.3888226, 0.3543486 2.144549, 0.3320178, 0.3884205 2.957854, 0.4967764, 0.3472340 ``` is a valid cross-sectional data set. Suppose this file is named `c:\cross-sectional-data.csv`. Then it can be loaded into R like this: ```{r, eval=FALSE} # Read content of file "C:\cross-sectional-data.csv" into object named # "serologyData". serologyData <- read.csv(file = "C:\\cross-sectional-data.csv") ``` ### 3.2.2. Specifying longitudinal response parameters {#longParams} The longitudinal response parameters set consists of the following items: - `y1`: antibody peak level (ELISA units) - `alpha`: antibody decay rate (1/days for the current longitudinal parameter sets) - `yb`: baseline antibody level at $t$ approaching infinity ($y(t->inf)$) - `r`: shape factor of antibody decay - `y0`: baseline antibody level at $t=0$ ($y(t=0)$) - `mu1`: initial antibody growth rate - `t1`: duration of infection Please, refer to vignette [methodology.pdf](methodology.pdf) for more details on the underlying methodology. End user has three options for loading the response parameters into R session: **i) Using supplied data** There are a few longitudinal response parameter data sets provided by the package including Monte-Carlo sample of longitudinal response parameters, like `campylobacterDelftParams4`. This particular object is a list containing three data.frame objects named `IgG`, `IgM` and `IgA`. Let's have a pick into each of these two data sets separately (notice character `$` indicating a sub-object of the parent object): ```{r} # Show first rows of data.frame "IgG" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgG) # Show first rows of data.frame "IgM" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgM) # Show first rows of data.frame "IgA" in list "campylobacterDelftParams4". head(campylobacterDelftParams4$IgA) ``` Let us assign object `campylobacterDelftParams4` to variable `responseParams`: ```{r} responseParams <- campylobacterDelftParams4 ``` **ii) Loading from local external files** Alternatively, this data can be loaded from an external file. Bear in mind, that most likely your data is organized into three files, separately for antibody `IgG`, `IgM` and `IgA`. Assuming that the data is saved into csv files named `IgG.csv`, `IgM.csv` and `IgA.csv` the end user would run the following code in order to create a valid input to the calculator: ```{r, eval=FALSE} IgGData <- read.csv(file = "IgG.csv") IgMData <- read.csv(file = "IgM.csv") IgAData <- read.csv(file = "IgA.csv") # Create a list named "responseData" containing objects named "IgG", "IgM" and # "IgA". responseParams <- list(IgG = IgGData, IgM = IgMData, IgA = IgAData) ``` Note that object `responseParams` is a list with three dataframes named `IgG`, `IgM` and `IgA` as required. **iii) Loading from an external repository** Finally, response parameters can be obtained from an online repository set up for this package. The repository is hosted on ECDC servers. At the time of publishing this package two files are available: a) `coxiellaIFAParams4.zip`: longitudinal response parameters per antibody for Coxiella. b) `yersiniaSSIParams4.zip`: longitudinal response parameters per antibody for Yersinia. Simply use the supplied utility function `getAdditionalData` to download this data: ```{r, eval=FALSE} responseParams <- getAdditionalData("coxiellaIFAParams4.zip") ``` Internet connection is needed for this function to work. ## 3.3. Estimating seroincidence Main calculation function provided by package *seroincidence* is called `estimateSeroincidence`. It takes several arguments: - `data`: A data frame with the cross-sectional data (see variable `serologyData` above). This may be the whole data set loaded from file, but can also be a subset, e.g. `data = serologyData[1, ]` to use only the first row. In this tutorial this is the data loaded into variable `serologyData`. It is a required input. - `antibodies`: A list of antibodies to be used. This can be a triplet (`antibodies = c("IgG", "IgM", "IgA")`) or any single antibody (`antibodies = c("IgG")`) or a combination of any two antibodies. It is a required input. - `strata`: A list of categories to stratify data. The column `AgeCat` in the example data set can be used as an example. If `strata = ""` (default), then the whole data set is treated as a single stratum; if each sample is assigned a unique identifier (e.g. `strata = "AgeCat"`) there are as many strata as there are samples and an incidence estimate is calculated for each sample. If not specified, then `strata` is initialized to `""`. - `params`: A list with the longitudinal parameters for all antibodies specified. In this tutorial this is the data loaded into variable `responseParams`. It is a required input. - `censorLimits`: A list of cutoff levels, one for each antibody used. These are antibody levels below which observations should be treated as censored. It is a required input. - `par0`: List of parameters for the (lognormal) distribution of antibody concentrations for true seronegatives (i.e. those who never seroconverted), by named antibody type (corresponding to `data`). - `start` A starting value for `log(lambda)`. Value of -6 corresponds roughly to 1 day (`log(1/365.25)`), value of -4 corresponds roughly to 1 week (`log(7/365.25)`). Users are adivised to experiment with this value to confirm that convergence to the same estimate is obtained. Default is -6. - `numCores` Number of processor cores to use for calculations when computing by `strata`. If set to more than 1 and R package `parallel` is available (installed by default), then the computations by stratum are executed in parallel. Default is 1, ie. no execution in parallel. Here is an example of the *Campylobacter* seroincidence calculation for three antibodies measured, stratified per `AgeCat`, and with measurements below `0.1` removed: ```{r, eval=FALSE} # Prepare input data. serologyData <- with(campylobacterSimMediumData, data.frame( Age = rep(NA, nrow(campylobacterSimMediumData)), IgG = IgG, IgM = IgM, IgA = IgA, AgeCat = cut(Age, 15, labels = FALSE))) responseParams <- campylobacterDelftParams4 cutOffs <- list(IgG = 0.1, IgM = 0.1, IgA = 0.1) # Baseline distributions: the distributions of antibody concentrations in # subjects who have never seroconverted. baseLine <- list(IgG = c(log(0.05), 1), IgM = c(log(0.005), 1), IgA = c(log(0.005), 1)) # Assign output of function "estimateSeroincidence" to object named # "seroincidenceData". Use all available processor cores. seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG", "IgM", "IgA"), strata = "AgeCat", params = responseParams, censorLimits = cutOffs, par0 = baseLine, start = -4, numCores = parallel::detectCores()) # Show content of the output variable... print(seroincidenceData) # ...or simply type in the console: 'seroincidenceData' (without "'") and # press ENTER. ``` The following text should be printed. ## Seroincidence object estimated given the following setup: ## a) Antibodies : IgG, IgM, IgA ## b) Strata : AgeCat ## c) Censor limits: IgG = 0.1, IgM = 0.1, IgA = 0.1 ## ## This object is a list containing the following items: ## Fits - List of outputs of "optim" function per stratum. ## Antibodies - Input parameter antibodies of function "estimateSeroincidence". ## Strata - Input parameter strata of function "estimateSeroincidence". ## CensorLimits - Input parameter censorLimits of function "estimateSeroincidence". ## ## Call summary function to obtain output results. The most important output is subobject `Fits` containing raw results on the output incidence. Translation of these raw results is provided by a custom function `summary` explained in the following section. The cutoff argument is based on censoring of the observed serum antibody measurements [@5]. Cut-off levels must always be specified when calling function `estimateSeroincidence` (argument `censorLimits`). Value `0` should be set for antibody measurements where no censoring is needed, for instance ```{r, eval=FALSE} censorLimits <- list(IgG = 0, IgM = 0, IgA = 0) ``` Using different censoring levels will produce different results. Choosing higher cut-off causes the estimates of lambda to decrease. Results should be published together with the chosen cut-off values. The cut-off level of `0.1` set in the example above is a typical value, but users should set it to value reflecting the censoring level in the data. ## 3.4. Getting a summary of seroincidence Output of the calculator should be passed in to function `summary` calculating output results: ```{r, eval=FALSE} summary(seroincidenceData) ``` ## Seroincidence estimated given the following setup: ## a) Antibodies : IgG, IgM, IgA ## b) Strata : AgeCat ## c) Censor limits: IgG = 0.1, IgM = 0.1, IgA = 0.1 ## d) Quantiles : 0.025, 0.975 ## ## Seroincidence estimates: ## Lambda.est Lambda.lwr Lambda.upr Deviance Convergence Stratum ## 1 0.09721890 0.06397004 0.14774909 105.29815 0 1 ## 2 0.05497303 0.03573489 0.08456817 181.90627 0 2 ## 3 0.04456096 0.02845903 0.06977327 199.99357 0 3 ## 4 0.02944038 0.01715302 0.05052964 141.32558 0 4 ## 5 0.02569781 0.01436524 0.04597053 123.33213 0 5 ## 6 0.02565297 0.01587275 0.04145941 187.41060 0 6 ## 7 0.03458616 0.02012722 0.05943207 128.84486 0 7 ## 8 0.02776873 0.02640621 0.02920154 133.57166 52 8 ## 9 0.04016261 0.02133209 0.07561541 94.99389 0 9 ## 10 0.01996477 0.01898409 0.02099612 104.30992 52 10 ## 11 0.03356017 0.01917771 0.05872886 141.20168 0 11 ## 12 0.05287648 0.03263923 0.08566140 181.68655 0 12 ## 13 0.05081097 0.02946963 0.08760729 123.66670 52 13 ## 14 0.04813104 0.02945312 0.07865371 186.92218 0 14 ## 15 0.03421042 0.02210895 0.05293569 215.78684 0 15 The `summary` function returns a list of objects as well. It contains sub-objects `Antibodies`, `Strata`, `CensorLimits`, `Quantiles` and `Results`. The most important sub-object of the output of the `summary` functions is `Results`, containing estimates of `Lambda` (annual incidence) together with their lower and upper bounds (`Lambda.lwr` and `Lambda.upr`, respectively). The default lower bound is 2.5% and the upper bound is 97.5% of the distribution of `Lambda`. These values can be changed (see [Other examples](#other-examples)). Optionally, the summary function returns also `Deviance` (negative log likelihood at the estimated `Lambda`) and `Convergence` (indicator returned by function `stats::optim`; value of 0 indicates convergence). It may be beneficial to assign output of this function to a variable for further analysis: ```{r, eval=FALSE} # Compute seroincidence summary and assign to object "seroincidenceSummary". seroincidenceSummary <- summary(seroincidenceData) # Show the results. seroincidenceSummary$Results ``` ## Lambda.est Lambda.lwr Lambda.upr Deviance Convergence Stratum ## 1 0.09721890 0.06397004 0.14774909 105.29815 0 1 ## 2 0.05497303 0.03573489 0.08456817 181.90627 0 2 ## 3 0.04456096 0.02845903 0.06977327 199.99357 0 3 ## 4 0.02944038 0.01715302 0.05052964 141.32558 0 4 ## 5 0.02569781 0.01436524 0.04597053 123.33213 0 5 ## 6 0.02565297 0.01587275 0.04145941 187.41060 0 6 ## 7 0.03458616 0.02012722 0.05943207 128.84486 0 7 ## 8 0.02776873 0.02640621 0.02920154 133.57166 52 8 ## 9 0.04016261 0.02133209 0.07561541 94.99389 0 9 ## 10 0.01996477 0.01898409 0.02099612 104.30992 52 10 ## 11 0.03356017 0.01917771 0.05872886 141.20168 0 11 ## 12 0.05287648 0.03263923 0.08566140 181.68655 0 12 ## 13 0.05081097 0.02946963 0.08760729 123.66670 52 13 ## 14 0.04813104 0.02945312 0.07865371 186.92218 0 14 ## 15 0.03421042 0.02210895 0.05293569 215.78684 0 15 As one may note it is a dataframe with six columns that can be later post-processed with custom calculations. # 4. Other examples The following examples show the standard procedure for estimating seroincidence. ```{r, eval=FALSE} # 1. Define cross-sectional data. serologyData <- with(campylobacterSimMediumData, data.frame( IgG = IgG.ratio.new, IgM = IgM.ratio.new, IgA = IgA.ratio.new)) # 2. Define longitudinal response data responseParams <- campylobacterDelftParams3 # 3. Define cut-offs cutOffs <- list(IgG = 0.25, IgM = 0.25, IgA = 0.25) # 4. Baseline distributions baseLine <- list(IgG = c(log(0.05), 1), IgM = c(log(0.005), 1), IgA = c(log(0.005), 1)) # 4a. Calculate a single seroincidence rate for all serum samples... seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG", "IgM", "IgA"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 4b. ...or calculate a single seroincidence rate for a single serum sample # (triplet of titres)... seroincidenceData <- estimateSeroincidence( data = serologyData[1, ], antibodies = c("IgG", "IgM", "IgA"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 4c. ...or calculate a single seroincidence rate for all serum samples (only IgG) seroincidenceData <- estimateSeroincidence( data = serologyData, antibodies = c("IgG"), strata = "", params = responseParams, censorLimits = cutOffs, par0 = baseLine) # 5a. Produce summary of the results with 2.5% and 97.5% bounds... summary(seroincidenceData) # 5b. ...or produce summary of the results with 5% and 95% bounds, do not show # convergence... summary(seroincidenceData, quantiles = c(0.05, 0.95), showConvergence = FALSE) # 5c. ...or produce summary and assign to an object... seroincidenceSummary <- summary(seroincidenceData) # ...and work with the results object from now on (here: display the results). seroincidenceSummary$Results ``` \newpage # Acknowledgements Project funded by European Centre for Disease Prevention and Control (ECDC). # References seroincidence/vignettes/cover.Rmd0000644000176200001440000000331313305506670016663 0ustar liggesusers--- title: "R Package - seroincidence" author: "European Centre for Disease Prevention and Control (ECDC)" output: rmarkdown::html_vignette: toc: yes vignette: > %\VignetteIndexEntry{R Package - seroincidence} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} --- ```{r, echo = FALSE} pkgVersion <- packageDescription("seroincidence")$Version pkgLicense <- packageDescription("seroincidence")$License pkgDate <- packageDescription("seroincidence")$Date authorsString <- gsub("^ *|(?<= ) |\n| *$", "", packageDescription("seroincidence")$Authors, perl = TRUE) authorList <- eval(parse(text = authorsString)) pkgAuthors <- paste(format(authorList, include = c("given", "family", "email", "comment"), braces = list(family = c("", ",
"), email = c("<", ">,
"), comment = c("", ""))), collapse = "

") pkgMaintainer <- packageDescription("seroincidence")$Maintainer pkgBaseFileName <- paste("seroincidence", pkgVersion, sep = "_") pkgUrl <- packageDescription("seroincidence")$URL ``` R package **seroincidence** allows translation of antibody levels measured in a (cross-sectional) population sample into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. Item | Data ----- | ------ Version | `r pkgVersion` Published | `r pkgDate` Authors | `r pkgAuthors` Maintainer | `r pkgMaintainer` License | `r pkgLicense` Installation manual | [installation.pdf](installation.pdf) Tutorial | [tutorial.pdf](tutorial.pdf) Appendix | [methodology.pdf](methodology.pdf) ECDC web site | `r pkgUrl` seroincidence/README.md0000644000176200001440000000134013273375665014362 0ustar liggesusersseroincidence package ===================== ------------------------------------------------------------------------ Antibody levels measured in a (cross–sectional) population sample can be translated into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. Formulated simply: the presence of many high titres indicates that many subjects likely experienced infection recently, while low titres indicate a low frequency of infections in the sampled population. 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*vignettes/methodology.Rmd 08e7c753fc50418d6d50a910c4edfbcb *vignettes/tutorial.Rmd seroincidence/build/0000755000176200001440000000000013305523607014167 5ustar liggesusersseroincidence/build/vignette.rds0000644000176200001440000000044413305523607016530 0ustar liggesusersRN0uDN,UWT]Xz±#ǥƇ#µФ |w锷16dA12` 1~H bLAkʚWHjڵ);>Oa%ӧ*ÕK<ɴ$qAZـ5N3q k_-bٷ}žgf&tԳpa@#rDd8W~/9,gZP6ks:w5TLxȖ}A׊seroincidence/DESCRIPTION0000644000176200001440000000316613305535606014606 0ustar liggesusersPackage: seroincidence Type: Package Title: Estimating Infection Rates from Serological Data Version: 2.0.0 Date: 2018-06-05 Authors@R: c( person(given = "Peter", family = "Teunis", email = "p.teunis@emory.edu", role = c("aut"), comment = "Author of the method and original code."), person(given = "Jan", family = "van Eijkeren", role = c("aut"), comment = "Author of the method and original code."), person(given = "Daniel", family = "Lewandowski", email = "daniel@nextpagesoft.net", role = c("com", "ctb"), comment = "Creator of the R package."), person(given = "Chantal", family = "Quinten", email = "seroincidence@ecdc.europa.eu", role = c("cre", "ctb"), comment = "Project manager and the package maintainer.")) Maintainer: Chantal Quinten Description: Translates antibody levels measured in a (cross-sectional) population sample into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. Depends: R (>= 2.10) License: GPL-3 Imports: stats, utils Suggests: knitr, rmarkdown, parallel VignetteBuilder: knitr LazyData: true Encoding: UTF-8 URL: https://ecdc.europa.eu/en/publications-data/seroincidence-calculator-tool RoxygenNote: 6.0.1 NeedsCompilation: no Packaged: 2018-06-05 15:09:00 UTC; Daniel Lewandowski Author: Peter Teunis [aut] (Author of the method and original code.), Jan van Eijkeren [aut] (Author of the method and original code.), Daniel Lewandowski [com, ctb] (Creator of the R package.), Chantal Quinten [cre, ctb] (Project manager and the package maintainer.) Repository: CRAN Date/Publication: 2018-06-05 16:34:14 UTC seroincidence/man/0000755000176200001440000000000013303571700013636 5ustar liggesusersseroincidence/man/salmonellaSSIParams2.Rd0000644000176200001440000000152213303571700020061 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{salmonellaSSIParams2} \alias{salmonellaSSIParams2} \title{Salmonella SSI Response Parameters Data for Model 2} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ salmonellaSSIParams2 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in salmonellaSSIParams2 lapply(salmonellaSSIParams2, head) } seroincidence/man/pertussisIgGPTParams3.Rd0000644000176200001440000000116313303571700020251 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{pertussisIgGPTParams3} \alias{pertussisIgGPTParams3} \title{Pertussis IgG-PT Response Parameters Data for Model 3} \format{A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody.} \usage{ pertussisIgGPTParams3 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in pertussisIgGPTParams3 lapply(pertussisIgGPTParams3, head) } seroincidence/man/campylobacterDelftParams4.Rd0000644000176200001440000000156013303571700021163 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterDelftParams4} \alias{campylobacterDelftParams4} \title{Campylobacter Delft Response Parameters Data for Model 4} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterDelftParams4 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in campylobacterDelftParams4 lapply(campylobacterDelftParams4, head) } seroincidence/man/campylobacterDelftParams1.Rd0000644000176200001440000000156013303571700021160 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterDelftParams1} \alias{campylobacterDelftParams1} \title{Campylobacter Delft Response Parameters Data for Model 1} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterDelftParams1 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in campylobacterDelftParams1 lapply(campylobacterDelftParams1, head) } seroincidence/man/pertussisIgGPTParams1.Rd0000644000176200001440000000116313303571700020247 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{pertussisIgGPTParams1} \alias{pertussisIgGPTParams1} \title{Pertussis IgG-PT Response Parameters Data for Model 1} \format{A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody.} \usage{ pertussisIgGPTParams1 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in pertussisIgGPTParams1 lapply(pertussisIgGPTParams1, head) } seroincidence/man/salmonellaSSIParams4.Rd0000644000176200001440000000152213303571700020063 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{salmonellaSSIParams4} \alias{salmonellaSSIParams4} \title{Salmonella SSI Response Parameters Data for Model 4} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ salmonellaSSIParams4 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in salmonellaSSIParams4 lapply(salmonellaSSIParams4, head) } seroincidence/man/campylobacterSSIParams4.Rd0000644000176200001440000000154413303571700020565 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterSSIParams4} \alias{campylobacterSSIParams4} \title{Campylobacter SSI Response Parameters Data for Model 4} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterSSIParams4 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in campylobacterSSIParams4 lapply(campylobacterSSIParams4, head) } seroincidence/man/campylobacterSSIParams2.Rd0000644000176200001440000000154313303571700020562 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterSSIParams2} \alias{campylobacterSSIParams2} \title{Campylobacter SSI Response Parameters Data for Model 2} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterSSIParams2 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type } \examples{ # Show first rows of every dataframe contained in campylobacterSSIParams2 lapply(campylobacterSSIParams2, head) } seroincidence/man/print.seroincidence.Rd0000644000176200001440000000150213272107427020076 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/print.seroincidence.R \name{print.seroincidence} \alias{print.seroincidence} \title{Print Method for Seroincidence Object} \usage{ \method{print}{seroincidence}(x, ...) } \arguments{ \item{x}{A list containing output of function \code{\link{estimateSeroincidence}}.} \item{...}{Additional arguments affecting the summary produced.} } \description{ Custom \code{\link{print}} function to show output of the seroincidence calculator \code{\link{estimateSeroincidence}}. } \examples{ \dontrun{ # estimate seroincidence seroincidence <- estimateSeroincidence(...) # print the seroincidence object to the console print(seroincidence) # or simply type (appropriate print method will be invoked automatically) seroincidence } } seroincidence/man/campylobacterDelftParams3.Rd0000644000176200001440000000156013303571700021162 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterDelftParams3} \alias{campylobacterDelftParams3} \title{Campylobacter Delft Response Parameters Data for Model 3} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterDelftParams3 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in campylobacterDelftParams3 lapply(campylobacterDelftParams3, head) } seroincidence/man/pertussisIgGPTParams4.Rd0000644000176200001440000000116313303571700020252 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{pertussisIgGPTParams4} \alias{pertussisIgGPTParams4} \title{Pertussis IgG-PT Response Parameters Data for Model 4} \format{A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody.} \usage{ pertussisIgGPTParams4 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in pertussisIgGPTParams4 lapply(pertussisIgGPTParams4, head) } seroincidence/man/campylobacterSimLowData.Rd0000644000176200001440000000156613303571700020707 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterSimLowData} \alias{campylobacterSimLowData} \alias{campylobacterSimMediumData} \alias{campylobacterSimHighData} \alias{pertussisSimLowData} \alias{pertussisSimMediumData} \alias{pertussisSimHighData} \title{Simulated Cross-sectional Data} \format{A data frame with 500 observations on the following 2 to 4 variables: \describe{ \item{Age}{} \item{IgG}{} \item{IgM}{} \item{IgA}{} }} \usage{ campylobacterSimLowData } \description{ Simulated cross-sectional population sample of antibody levels data for Campylobacter and Pertussis for lambda 0.036/yr (low), 0.021/yr (medium) and 1.15/yr (high). } \examples{ # Show first rows of the data head(campylobacterSimLowData) # Summarize the data summary(campylobacterSimLowData) } seroincidence/man/salmonellaSSIParams1.Rd0000644000176200001440000000152213303571700020060 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{salmonellaSSIParams1} \alias{salmonellaSSIParams1} \title{Salmonella SSI Response Parameters Data for Model 1} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 3000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 3000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 3000 rows with 7 parameters for IgG antibody.} }} \usage{ salmonellaSSIParams1 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in salmonellaSSIParams1 lapply(salmonellaSSIParams1, head) } seroincidence/man/print.summary.seroincidence.Rd0000644000176200001440000000175713272107427021606 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/print.summary.seroincidence.R \name{print.summary.seroincidence} \alias{print.summary.seroincidence} \title{Print Method for Seroincidence Summary Object} \usage{ \method{print}{summary.seroincidence}(x, ...) } \arguments{ \item{x}{A list containing output of function \code{\link{summary.seroincidence}}.} \item{...}{Additional arguments affecting the summary produced.} } \description{ Custom \code{\link{print}} function to show output of the seroincidence summary \code{\link{summary.seroincidence}}. } \examples{ \dontrun{ # estimate seroincidence seroincidence <- estimateSeroincidence(...) # calculate summary statistics for the seroincidence object seroincidenceSummary <- summary(seroincidence) # print the summary of seroincidence object to the console print(seroincidenceSummary) # or simply type (appropriate print method will be invoked automatically) seroincidenceSummary } } seroincidence/man/summary.seroincidence.Rd0000644000176200001440000000427613304210226020436 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/summary.seroincidence.R \name{summary.seroincidence} \alias{summary.seroincidence} \title{Summary Method for Seroincidence Object} \usage{ \method{summary}{seroincidence}(object, ..., quantiles = c(0.025, 0.975), showDeviance = TRUE, showConvergence = TRUE) } \arguments{ \item{object}{A dataframe containing output of function \code{\link{estimateSeroincidence}}.} \item{...}{Additional arguments affecting the summary produced.} \item{quantiles}{A vector of length 2 specifying quantiles for lower (first element) and upper (second element) bounds of \code{lambda}. Default = \code{c(0.025, 0.975)}.} \item{showDeviance}{Logical flag (\code{FALSE}/\code{TRUE}) for reporting deviance (-2*log(likelihood) at estimated seroincidence. Default = \code{TRUE}.} \item{showConvergence}{Logical flag (\code{FALSE}/\code{TRUE}) for reporting convergence (see help for \code{\link{optim}} for details). Default = \code{TRUE}.} } \value{ A list with the following items: \describe{ \item{\code{Results}}{Dataframe with maximum likelihood estimate of \code{lambda} (the seroincidence) (column \code{Lambda}) and corresponding lower (\code{Lambda.lwr}) and upper (\code{Lambda.upr} bounds.\cr Optionally \code{Deviance} (Negative log likelihood (NLL) at estimated (maximum likelihood) \code{lambda}) and \code{Covergence} (Convergence indicator returned by \code{\link{optim}}. Value of 0 indicates convergence) columns are included.} \item{\code{Antibodies}}{Character vector with names of input antibodies used in \code{\link{estimateSeroincidence}}.} \item{\code{Strata}}{Character with names of strata used in \code{\link{estimateSeroincidence}}.} \item{\code{CensorLimits}}{List of cutoffs for each of the antibodies used in \code{\link{estimateSeroincidence}}.} } } \description{ Calculate seroincidence from output of the seroincidence calculator \code{\link{estimateSeroincidence}}. } \examples{ \dontrun{ # estimate seroincidence seroincidence <- estimateSeroincidence(...) # calculate summary statistics for the seroincidence object seroincidenceSummary <- summary(seroincidence) } } seroincidence/man/campylobacterSSIParams1.Rd0000644000176200001440000000154313303571700020561 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{campylobacterSSIParams1} \alias{campylobacterSSIParams1} \title{Campylobacter SSI Response Parameters Data for Model 1} \format{A list of three dataframes: \describe{ \item{\code{IgA}}{A dataframe containing 4000 rows with 7 parameters for IgA antibody.} \item{\code{IgM}}{A dataframe containing 4000 rows with 7 parameters for IgM antibody.} \item{\code{IgG}}{A dataframe containing 4000 rows with 7 parameters for IgG antibody.} }} \usage{ campylobacterSSIParams1 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type } \examples{ # Show first rows of every dataframe contained in campylobacterSSIParams1 lapply(campylobacterSSIParams1, head) } seroincidence/man/pertussisIgGPTParams2.Rd0000644000176200001440000000116313303571700020250 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/data-help.R \docType{data} \name{pertussisIgGPTParams2} \alias{pertussisIgGPTParams2} \title{Pertussis IgG-PT Response Parameters Data for Model 2} \format{A dataframe \code{IgG} containing 3000 rows with 7 parameters for IgG antibody.} \usage{ pertussisIgGPTParams2 } \description{ List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type. } \examples{ # Show first rows of every dataframe contained in pertussisIgGPTParams2 lapply(pertussisIgGPTParams2, head) } seroincidence/man/estimateSeroincidence.Rd0000644000176200001440000000462113305423060020433 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/estimateSeroincidence.R \name{estimateSeroincidence} \alias{estimateSeroincidence} \title{Estimate Seroincidence} \usage{ estimateSeroincidence(data, antibodies, strata = "", params, censorLimits, par0, start = -6, numCores = 1L) } \arguments{ \item{data}{Data frame with cross-sectional serology data per antibody and age, and additional columns to identify possible \code{strata}.} \item{antibodies}{Character vector with one or more antibody names. Values must match \code{data}.} \item{strata}{Character vector of strata. Values must match with \code{data}. Default = "".} \item{params}{List of data frames of all longitudinal parameters. Each data frame contains Monte Carlo samples for each antibody type.} \item{censorLimits}{List of cutoffs for one or more named antibody types (corresponding to \code{data}).} \item{par0}{List of parameters for the (lognormal) distribution of antibody concentrations for true seronegatives (i.e. those who never seroconverted), by named antibody type (corresponding to \code{data}).} \item{start}{A starting value for \code{log(lambda)}. Value of -6 corresponds roughly to 1 day (log(1/365.25)), -4 corresponds roughly to 1 week (log(7 / 365.25)). Default = -6.} \item{numCores}{Number of processor cores to use for calculations when computing by strata. If set to more than 1 and package \pkg{parallel} is available, then the computations are executed in parallel. Default = 1L.} } \value{ A set of lambda estimates for each strata. } \description{ Function to estimate seroincidences based on cross-section serology data and longitudinal response model. } \examples{ \dontrun{ estimateSeroincidence(data = csData, antibodies = c("IgG", "IgM", "IgA"), strata = "", params = campylobacterDelftParams4, censorLimits = cutOffs, par0 = baseLn, start = -4) estimateSeroincidence(data = csData, antibodies = c("IgG", "IgM", "IgA"), strata = "", params = campylobacterDelftParams4, censorLimits = cutOffs, par0 = baseLn, start = -4, numCores = parallel::detectCores()) } } seroincidence/man/getAdditionalData.Rd0000644000176200001440000000234213304210045017461 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/getAdditionalData.R \name{getAdditionalData} \alias{getAdditionalData} \title{Get Additional Data} \usage{ getAdditionalData(fileName, repoURL = "http://ecdc.europa.eu/sites/portal/files/documents", savePath = NULL) } \arguments{ \item{fileName}{Name of the file to download. Required.} \item{repoURL}{Web address of the remote repository of files to download from. Required. Default = \code{"http://ecdc.europa.eu/sites/portal/files/documents"}} \item{savePath}{Folder to save the downloaded and unzipped (if needed) file. File is saved only if this argument is not \code{NULL}. Optional. Default = \code{NULL}.} } \value{ Data object } \description{ Retrieves additional data from internet. This can be any file type, but the purpose of this function is to download data such as longitudinal response parameters from an online repository. } \examples{ \dontrun{ getAdditionalData(fileName = "coxiellaIFAParams4.zip") getAdditionalData(fileName = "yersiniaSSIParams4.zip") getAdditionalData(fileName = "coxiellaIFAParams4.zip", savePath = getwd()) getAdditionalData(fileName = "yersiniaSSIParams4.zip", savePath = getwd()) } } seroincidence/man/seroincidence.Rd0000644000176200001440000001231213302455573016746 0ustar liggesusers% Generated by roxygen2: do not edit by hand % Please edit documentation in R/seroincidence-package.R \docType{package} \name{seroincidence} \alias{seroincidence} \alias{seroincidence-package} \alias{seroincidence-package} \title{Estimating Infection Rates from Serological Data} \description{ Translates antibody levels measured in a (cross-sectional) population sample into an estimate of the frequency with which seroconversions (infections) occur in the sampled population. } \details{ For detailed documentation type the following in the R console:\cr \code{vignette("installation", package = "seroincidence")}\cr \code{vignette("tutorial", package = "seroincidence")}\cr \code{vignette("methodology", package = "seroincidence")} } \references{ \strong{\emph{Methods for estimating seroincidence}} \itemize{ \item Teunis, P. F., van Eijkeren, J. C., Ang, C. W., van Duynhoven, Y. T., Simonsen, J. B., Strid, M. A., van Pelt, W.\cr "Biomarker dynamics: estimating infection rates from serological data"\cr Statistics in Medicine 31, no. 20 (September 9, 2012): 2240--48. doi:10.1002/sim.5322. \item Simonsen, J., Molbak, K., Falkenhorst, G., Krogfelt, K. A., Linneberg, A., Teunis, P. F.\cr "Estimation of incidences of infectious diseases based on antibody measurements"\cr Statistics in Medicine 28, no. 14 (June 30, 2009): 1882--95. doi:10.1002/sim.3592. } \strong{\emph{Applications}} \itemize{ \item Monge, S., Teunis, P. F., Friesema, I., Franz, E., Ang, W., van Pelt, W., Mughini-Gras, L.\cr "Immune response-eliciting exposure to Campylobacter vastly exceeds the incidence of clinically overt campylobacteriosis but is associated with similar risk factors: A nationwide serosurvey in the Netherlands"\cr Journal of Infection, 2018, 1--7, doi:10.1016/j.jinf.2018.04.016 \item Kretzschmar, M., Teunis, P. F., Pebody, R. G.\cr "Incidence and reproduction numbers of pertussis: estimates from serological and social contact data in five European countries"\cr PLoS Medicine 7, no. 6 (June 1, 2010):e1000291. doi:10.1371/journal.pmed.1000291. \item Simonsen, J., Strid, M. A., Molbak, K., Krogfelt, K. A., Linneberg, A., Teunis, P.\cr "Sero-epidemiology as a tool to study the incidence of Salmonella infections in humans"\cr Epidemiology and Infection 136, no. 7 (July 1, 2008): 895--902. doi:10.1017/S0950268807009314 \item Simonsen, J., Teunis, P. F., van Pelt, W., van Duynhoven, Y., Krogfelt, K. A., Sadkowska-Todys, M., Molbak K.\cr "Usefulness of seroconversion rates for comparing infection pressures between countries"\cr Epidemiology and Infection, April 12, 2010, 1--8. doi:10.1017/S0950268810000750. \item Falkenhorst, G., Simonsen, J., Ceper, T. H., van Pelt, W., de Valk, H., Sadkowska-Todys, M., Zota, L., Kuusi, M., Jernberg, C., Rota, M. C., van Duynhoven, Y. T., Teunis, P. F., Krogfelt, K. A., Molbak, K.\cr "Serological cross-sectional studies on salmonella incidence in eight European countries: no correlation with incidence of reported cases"\cr BMC Public Health 12, no. 1 (July 15, 2012): 523--23. doi:10.1186/1471-2458-12-523. \item Teunis, P. F., Falkenhorst, G., Ang, C. W., Strid, M. A., De Valk, H., Sadkowska-Todys, M., Zota, L., Kuusi, M., Rota, M. C., Simonsen, J. B., Molbak, K., Van Duynhoven, Y. T., van Pelt, W.\cr "Campylobacter seroconversion rates in selected countries in the European Union"\cr Epidemiology and Infection 141, no. 10 (2013): 2051--57. doi:10.1017/S0950268812002774. \item de Melker, H. E., Versteegh, F. G., Schellekens, J. F., Teunis, P. F., Kretzschmar, M.\cr "The incidence of Bordetella pertussis infections estimated in the population from a combination of serological surveys"\cr The Journal of Infection 53, no. 2 (August 1, 2006): 106--13. doi:10.1016/j.jinf.2005.10.020 } \strong{\emph{Quantification of seroresponse}} \itemize{ \item de Graaf, W. F., Kretzschmar, M. E., Teunis, P. F., Diekmann, O.\cr "A two-phase within-host model for immune response and its application to serological profiles of pertussis"\cr Epidemics 9 (2014):1--7. doi:10.1016/j.epidem.2014.08.002. \item Berbers, G. A., van de Wetering, M. S., van Gageldonk, P. G., Schellekens, J. F., Versteegh, F. G., Teunis, P.F.\cr "A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens"\cr Vaccine 31, no. 36 (August 12, 2013): 3732--38. doi:10.1016/j.vaccine.2013.05.073. \item Versteegh, F. G., Mertens, P. L., de Melker, H. E., Roord, J. J., Schellekens, J. F., Teunis, P. F.\cr "Age-specific long-term course of IgG antibodies to pertussis toxin after symptomatic infection with Bordetella pertussis"\cr Epidemiology and Infection 133, no. 4 (August 1, 2005): 737--48. \item Teunis, P. F., van der Heijden, O. G., de Melker, H. E., Schellekens, J. F., Versteegh, F. G., Kretzschmar, M. E. "Kinetics of the IgG antibody response to pertussis toxin after infection with B. pertussis"\cr Epidemiology and Infection 129, no. 3 (December 10, 2002):479. doi:10.1017/S0950268802007896. } } \author{ Author: Peter Teunis \email{}\cr Author: Jan van Eijkeren\cr Contributor: Daniel Lewandowski \email{}\cr Maintainer: Chantal Quinten \email{} }