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} </style> <!-- Add a small amount of space between sections. --> <style type="text/css"> div.section { padding-top: 12px; } </style> <div class="fluid-row" id="header"> <h1 class="title toc-ignore">Distribution of eQTL sharing across tissues</h1> <h4 class="author"><em>Sarah Urbut, Gao Wang, Peter Carbonetto and Matthew Stephens</em></h4> </div> <p><strong>Last updated:</strong> 2018-06-06</p> <strong>workflowr checks:</strong> <small>(Click a bullet for more information)</small> <ul> <li> <p><details> <summary> <strong style="color:blue;">✔</strong> <strong>R Markdown file:</strong> up-to-date </summary></p> <p>Great! Since the R Markdown file has been committed to the Git repository, you know the exact version of the code that produced these results.</p> </details> </li> <li> <p><details> <summary> <strong style="color:blue;">✔</strong> <strong>Environment:</strong> empty </summary></p> <p>Great job! The global environment was empty. Objects defined in the global environment can affect the analysis in your R Markdown file in unknown ways. For reproduciblity it’s best to always run the code in an empty environment.</p> </details> </li> <li> <p><details> <summary> <strong style="color:blue;">✔</strong> <strong>Seed:</strong> <code>set.seed(1)</code> </summary></p> <p>The command <code>set.seed(1)</code> was run prior to running the code in the R Markdown file. 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The version displayed above was the version of the Git repository at the time these results were generated. <br><br> Note that you need to be careful to ensure that all relevant files for the analysis have been committed to Git prior to generating the results (you can use <code>wflow_publish</code> or <code>wflow_git_commit</code>). workflowr only checks the R Markdown file, but you know if there are other scripts or data files that it depends on. Below is the status of the Git repository when the results were generated: <pre><code> Ignored files: Ignored: .sos/ Ignored: data/.sos/ Ignored: output/MatrixEQTLSumStats.Portable.Z.coved.K3.P3.lite.single.expanded.V1.loglik.rds Ignored: workflows/.ipynb_checkpoints/ Ignored: workflows/.sos/ Untracked files: Untracked: fastqtl_to_mash_output/ Untracked: gtex6_workflow_output/ Unstaged changes: Modified: analysis/Tspecific.Rmd Modified: analysis/gtex.Rmd </code></pre> Note that any generated files, e.g. HTML, png, CSS, etc., are not included in this status report because it is ok for generated content to have uncommitted changes. </details> </li> </ul> <details> <summary> <small><strong>Expand here to see past versions:</strong></small> </summary> <ul> <table style="border-collapse:separate; border-spacing:5px;"> <thead> <tr> <th style="text-align:left;"> File </th> <th style="text-align:left;"> Version </th> <th style="text-align:left;"> Author </th> <th style="text-align:left;"> Date </th> <th style="text-align:left;"> Message </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;"> Rmd </td> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/0226fe3288a183d5626d077010c86d7573eabd44/analysis/SharingHist.Rmd" target="_blank">0226fe3</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> wflow_publish(“SharingHist.Rmd”) </td> </tr> <tr> <td style="text-align:left;"> Rmd </td> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/ddd3bd368e5ffd5eb6a8eb5c52f33af448d4157b/analysis/SharingHist.Rmd" target="_blank">ddd3bd3</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> wflow_publish(“SharingHist.Rmd”) </td> </tr> <tr> <td style="text-align:left;"> html </td> <td style="text-align:left;"> <a href="https://cdn.rawgit.com/stephenslab/gtexresults/0c91e3fbf4d3e552b281a8321a071a36ec88394d/docs/SharingHist.html" target="_blank">0c91e3f</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> I have a first complete revision of the SharingHist analysis without </td> </tr> <tr> <td style="text-align:left;"> Rmd </td> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/0f4a56abd4c3a2be4a6330113c25195342d14f1f/analysis/SharingHist.Rmd" target="_blank">0f4a56a</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> wflow_publish(“SharingHist.Rmd”) </td> </tr> <tr> <td style="text-align:left;"> Rmd </td> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/9ee901fc33d3d847a808c48e0d09b43dc6ce3126/analysis/SharingHist.Rmd" target="_blank">9ee901f</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> Revised data/results loading steps in HeterogeneityTables.Rmd. </td> </tr> <tr> <td style="text-align:left;"> Rmd </td> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/d199d6626f1890ad53dced3b79065d20bb2c40a0/analysis/SharingHist.Rmd" target="_blank">d199d66</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> <td style="text-align:left;"> wflow_publish(“Tspecific.Rmd”) </td> </tr> </tbody> </table> </ul> <p></details></p> <hr /> <p>Here we develop another summary of sharing of eQTLs across tissues by showing the estimated distribution of sharing; specifically, the distribution of the number of tissues shared by sign and by magnitude. This complements <a href="HeterogeneityTables.html">this summary</a> and <a href="Tspecific.html">this one</a>.</p> <p>Compare the plots below to the plots in Figure 5 of the paper.</p> <div id="set-up-environment" class="section level2"> <h2>Set up environment</h2> <p>First, we load some functions defined for the mash analyses.</p> <pre class="r"><code>source("../code/normfuncs.R")</code></pre> <p>This is the threshold used to determine whether a gene has an eQTL in a given tissue.</p> <pre class="r"><code>thresh <- 0.05</code></pre> </div> <div id="load-data-and-mash-results" class="section level2"> <h2>Load data and mash results</h2> <p>Load some GTEx summary statistics, as well as some of the results generated from the mash analysis of the GTEx data.</p> <pre class="r"><code>out <- readRDS("../data/MatrixEQTLSumStats.Portable.Z.rds") maxbeta <- out$test.b maxz <- out$test.z out <- readRDS(paste("../output/MatrixEQTLSumStats.Portable.Z.coved.K3.P3", "lite.single.expanded.V1.posterior.rds",sep = ".")) lfsr <- out$lfsr pm.mash <- out$posterior.means standard.error <- maxbeta/maxz pm.mash.beta <- pm.mash * standard.error</code></pre> </div> <div id="histograms-of-sharing-by-magnitude" class="section level1"> <h1>Histograms of sharing by magnitude</h1> <p>Sharing by magnitude means that two eQTLs have similar effect size (within a factor of 2).</p> <p>Here we plot histograms of sharing by magnitude across all tissues (left), tissues other than brain (middle), and brain tissues only (right).</p> <pre class="r"><code>sigmat <- (lfsr <= thresh) nsig <- rowSums(sigmat) par(mar = c(4,4,2,1)) par(oma = c(8,4,0,0) + 0.1) par(mfrow = c(1,3)) hist((het.func(het.norm(effectsize=pm.mash.beta[nsig>0,]),threshold=0.5)), main="",xlab="",breaks=0.5:44.5,col="grey",freq=FALSE,ylim=c(0,0.9), xaxt="n") axis(1,at = seq(1, 44, by=1),labels = c(1:44)) mtext("All Tissues") sigmat <- (lfsr[,-c(7:16)] <= thresh) nsig <- rowSums(sigmat) hist((het.func(het.norm(effectsize=pm.mash.beta[nsig>0,-c(7:16)]), threshold=0.5)),main="",xlab="",breaks=0.5:34.5,col="grey", freq=FALSE,ylim=c(0,0.9),xaxt="n") axis(1,at = seq(1, 34, by=1),labels = c(1:34)) mtext("Non-Brain Tissues") sigmat <- (lfsr[,c(7:16)]<=thresh) nsig <- rowSums(sigmat) brain.norm <- het.norm(effectsize=pm.mash.beta[nsig>0,c(7:16)]) hist(het.func(brain.norm,threshold=0.5),main="",xlab="",breaks=0.5:10.5, col="grey",freq=FALSE,xaxt="n",ylim=c(0,0.9)) axis(1, at=seq(1, 10, by=1), labels=c(1:10)) mtext("Brain Tissues")</code></pre> <p><img src="figure/SharingHist.Rmd/hindex-plot-magnitude-1.png" width="768" style="display: block; margin: auto;" /></p> <details> <summary><em>Expand here to see past versions of hindex-plot-magnitude-1.png:</em></summary> <table style="border-collapse:separate; border-spacing:5px;"> <thead> <tr> <th style="text-align:left;"> Version </th> <th style="text-align:left;"> Author </th> <th style="text-align:left;"> Date </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/0c91e3fbf4d3e552b281a8321a071a36ec88394d/docs/figure/SharingHist.Rmd/hindex-plot-magnitude-1.png" target="_blank">0c91e3f</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> </tr> </tbody> </table> <p></details></p> <p>Observe that the distribution of the number of tissues in which an eQTL is shared by magnitude has a mode at 1. This is a subset of eQTLs that have much stronger effect in one tissue than in any other (“tissue-specific”).</p> <div id="histogram-of-sharing-by-magnitude" class="section level2"> <h2>Histogram of sharing by magnitude</h2> <p>Sharing by sign means that the eQTLs have the same sign of effect.</p> <p>Here we plot histograms of sharing by sign across all tissues (left), tissues other than brain (middle), and brain tissues only (right).</p> <pre class="r"><code>sign.func <- function (normeffectsize) apply(normeffectsize,1,function(x)(sum(x>0))) sigmat <- (lfsr<=thresh) nsig <- rowSums(sigmat) par(mar = c(4,4.5,2,1)) par(oma = c(8,4,0,0) + 0.1) par(mfrow = c(1,3)) hist(sign.func(het.norm(effectsize=pm.mash.beta[nsig>0,])),main="",xlab="", breaks=0.5:44.5,col="grey",freq=FALSE,xaxt="n",ylim=c(0,0.9)) axis(1, at=seq(1, 44, by=1), labels=c(1:44)) mtext("All Tissues") sigmat <- (lfsr[,-c(7:16)] <= thresh) nsig <- rowSums(sigmat) hist(sign.func(het.norm(effectsize = pm.mash.beta[nsig>0,-c(7:16)])), main="",xlab="",breaks=0.5:34.5,col="grey",freq=FALSE,ylim=c(0,0.9), xaxt="n") axis(1, at=seq(1, 34, by=1), labels=c(1:34)) mtext("Non-Brain Tissues") sigmat <- (lfsr[,c(7:16)]<=thresh) nsig <- rowSums(sigmat) brain.norm <- het.norm(effectsize=pm.mash.beta[nsig>0,c(7:16)]) hist(sign.func(brain.norm),main="",xlab="",breaks=0.5:10.5,col="grey", freq=FALSE,xaxt="n",ylim=c(0,0.9)) axis(1, at=seq(1, 10, by=1), labels=c(1:10)) mtext("Brain Tissues")</code></pre> <p><img src="figure/SharingHist.Rmd/hindex-plot-sign-1.png" width="768" style="display: block; margin: auto;" /></p> <details> <summary><em>Expand here to see past versions of hindex-plot-sign-1.png:</em></summary> <table style="border-collapse:separate; border-spacing:5px;"> <thead> <tr> <th style="text-align:left;"> Version </th> <th style="text-align:left;"> Author </th> <th style="text-align:left;"> Date </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;"> <a href="https://github.com/stephenslab/gtexresults/blob/0c91e3fbf4d3e552b281a8321a071a36ec88394d/docs/figure/SharingHist.Rmd/hindex-plot-sign-1.png" target="_blank">0c91e3f</a> </td> <td style="text-align:left;"> Peter Carbonetto </td> <td style="text-align:left;"> 2018-06-06 </td> </tr> </tbody> </table> <p></details></p> <p>Similar to other summaries of the mash analysis, we see that eQTLs exhibit a high level of sharing across tissues.</p> </div> <div id="session-information" class="section level2"> <h2>Session information</h2> <pre class="r"><code>sessionInfo() # R version 3.4.3 (2017-11-30) # Platform: x86_64-apple-darwin15.6.0 (64-bit) # Running under: macOS High Sierra 10.13.4 # # Matrix products: default # BLAS: /Library/Frameworks/R.framework/Versions/3.4/Resources/lib/libRblas.0.dylib # LAPACK: /Library/Frameworks/R.framework/Versions/3.4/Resources/lib/libRlapack.dylib # # locale: # [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8 # # attached base packages: # [1] stats graphics grDevices utils datasets methods base # # loaded via a namespace (and not attached): # [1] workflowr_1.0.1.9000 Rcpp_0.12.16 digest_0.6.15 # [4] rprojroot_1.3-2 R.methodsS3_1.7.1 backports_1.1.2 # [7] git2r_0.21.0 magrittr_1.5 evaluate_0.10.1 # [10] stringi_1.1.7 whisker_0.3-2 R.oo_1.21.0 # [13] R.utils_2.6.0 rmarkdown_1.9 tools_3.4.3 # [16] stringr_1.3.0 yaml_2.1.18 compiler_3.4.3 # [19] htmltools_0.3.6 knitr_1.20</code></pre> </div> </div> <script type="text/x-mathjax-config"> MathJax.Hub.Config({ "HTML-CSS": { availableFonts: ["TeX"] } }); </script> <!-- Adjust MathJax settings so that all math formulae are shown using TeX fonts only; see http://docs.mathjax.org/en/latest/configuration.html. 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