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index.html
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<!DOCTYPE html>
<html lang="en"><head>
<script src="index_files/libs/clipboard/clipboard.min.js"></script>
<script src="index_files/libs/quarto-html/tabby.min.js"></script>
<script src="index_files/libs/quarto-html/popper.min.js"></script>
<script src="index_files/libs/quarto-html/tippy.umd.min.js"></script>
<link href="index_files/libs/quarto-html/tippy.css" rel="stylesheet">
<link href="index_files/libs/quarto-html/quarto-html.min.css" rel="stylesheet" data-mode="light">
<link href="index_files/libs/quarto-html/quarto-syntax-highlighting.css" rel="stylesheet" id="quarto-text-highlighting-styles"><meta charset="utf-8">
<meta name="generator" content="quarto-1.0.36">
<title>index</title>
<meta name="apple-mobile-web-app-capable" content="yes">
<meta name="apple-mobile-web-app-status-bar-style" content="black-translucent">
<meta name="viewport" content="width=device-width, initial-scale=1.0, maximum-scale=1.0, user-scalable=no, minimal-ui">
<link rel="stylesheet" href="index_files/libs/revealjs/dist/reset.css">
<link rel="stylesheet" href="index_files/libs/revealjs/dist/reveal.css">
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
pre > code.sourceCode { white-space: pre; position: relative; }
pre > code.sourceCode > span { display: inline-block; line-height: 1.25; }
pre > code.sourceCode > span:empty { height: 1.2em; }
.sourceCode { overflow: visible; }
code.sourceCode > span { color: inherit; text-decoration: inherit; }
div.sourceCode { margin: 1em 0; }
pre.sourceCode { margin: 0; }
@media screen {
div.sourceCode { overflow: auto; }
}
@media print {
pre > code.sourceCode { white-space: pre-wrap; }
pre > code.sourceCode > span { text-indent: -5em; padding-left: 5em; }
}
pre.numberSource code
{ counter-reset: source-line 0; }
pre.numberSource code > span
{ position: relative; left: -4em; counter-increment: source-line; }
pre.numberSource code > span > a:first-child::before
{ content: counter(source-line);
position: relative; left: -1em; text-align: right; vertical-align: baseline;
border: none; display: inline-block;
-webkit-touch-callout: none; -webkit-user-select: none;
-khtml-user-select: none; -moz-user-select: none;
-ms-user-select: none; user-select: none;
padding: 0 4px; width: 4em;
color: #aaaaaa;
}
pre.numberSource { margin-left: 3em; border-left: 1px solid #aaaaaa; padding-left: 4px; }
div.sourceCode
{ color: #003b4f; background-color: #f1f3f5; }
@media screen {
pre > code.sourceCode > span > a:first-child::before { text-decoration: underline; }
}
code span { color: #003b4f; } /* Normal */
code span.al { color: #ad0000; } /* Alert */
code span.an { color: #5e5e5e; } /* Annotation */
code span.at { color: #657422; } /* Attribute */
code span.bn { color: #ad0000; } /* BaseN */
code span.bu { } /* BuiltIn */
code span.cf { color: #003b4f; } /* ControlFlow */
code span.ch { color: #20794d; } /* Char */
code span.cn { color: #8f5902; } /* Constant */
code span.co { color: #5e5e5e; } /* Comment */
code span.cv { color: #5e5e5e; font-style: italic; } /* CommentVar */
code span.do { color: #5e5e5e; font-style: italic; } /* Documentation */
code span.dt { color: #ad0000; } /* DataType */
code span.dv { color: #ad0000; } /* DecVal */
code span.er { color: #ad0000; } /* Error */
code span.ex { } /* Extension */
code span.fl { color: #ad0000; } /* Float */
code span.fu { color: #4758ab; } /* Function */
code span.im { color: #00769e; } /* Import */
code span.in { color: #5e5e5e; } /* Information */
code span.kw { color: #003b4f; } /* Keyword */
code span.op { color: #5e5e5e; } /* Operator */
code span.ot { color: #003b4f; } /* Other */
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code span.wa { color: #5e5e5e; font-style: italic; } /* Warning */
</style>
<link rel="stylesheet" href="index_files/libs/revealjs/dist/theme/quarto.css" id="theme">
<link href="index_files/libs/revealjs/plugin/quarto-line-highlight/line-highlight.css" rel="stylesheet">
<link href="index_files/libs/revealjs/plugin/reveal-menu/menu.css" rel="stylesheet">
<link href="index_files/libs/revealjs/plugin/reveal-menu/quarto-menu.css" rel="stylesheet">
<link href="index_files/libs/revealjs/plugin/quarto-support/footer.css" rel="stylesheet">
<style type="text/css">
.callout {
margin-top: 1em;
margin-bottom: 1em;
border-radius: .25rem;
}
.callout.callout-style-simple {
padding: 0em 0.5em;
border-left: solid #acacac .3rem;
border-right: solid 1px silver;
border-top: solid 1px silver;
border-bottom: solid 1px silver;
display: flex;
}
.callout.callout-style-default {
border-left: solid #acacac .3rem;
border-right: solid 1px silver;
border-top: solid 1px silver;
border-bottom: solid 1px silver;
}
.callout .callout-body-container {
flex-grow: 1;
}
.callout.callout-style-simple .callout-body {
font-size: 1rem;
font-weight: 400;
}
.callout.callout-style-default .callout-body {
font-size: 0.9rem;
font-weight: 400;
}
.callout.callout-captioned.callout-style-simple .callout-body {
margin-top: 0.2em;
}
.callout:not(.callout-captioned) .callout-body {
display: flex;
}
.callout:not(.no-icon).callout-captioned.callout-style-simple .callout-content {
padding-left: 1.6em;
}
.callout.callout-captioned .callout-header {
padding-top: 0.2em;
margin-bottom: -0.2em;
}
.callout.callout-captioned .callout-caption p {
margin-top: 0.5em;
margin-bottom: 0.5em;
}
.callout.callout-captioned.callout-style-simple .callout-content p {
margin-top: 0;
}
.callout.callout-captioned.callout-style-default .callout-content p {
margin-top: 0.7em;
}
.callout.callout-style-simple div.callout-caption {
border-bottom: none;
font-size: .9rem;
font-weight: 600;
opacity: 75%;
}
.callout.callout-style-default div.callout-caption {
border-bottom: none;
font-weight: 600;
opacity: 85%;
font-size: 0.9rem;
padding-left: 0.5em;
padding-right: 0.5em;
}
.callout.callout-style-default div.callout-content {
padding-left: 0.5em;
padding-right: 0.5em;
}
.callout.callout-style-simple .callout-icon::before {
height: 1rem;
width: 1rem;
display: inline-block;
content: "";
background-repeat: no-repeat;
background-size: 1rem 1rem;
}
.callout.callout-style-default .callout-icon::before {
height: 0.9rem;
width: 0.9rem;
display: inline-block;
content: "";
background-repeat: no-repeat;
background-size: 0.9rem 0.9rem;
}
.callout-caption {
display: flex
}
.callout-icon::before {
margin-top: 1rem;
padding-right: .5rem;
}
.callout.no-icon::before {
display: none !important;
}
.callout.callout-captioned .callout-body > .callout-content > :last-child {
margin-bottom: 0.5rem;
}
.callout.callout-captioned .callout-icon::before {
margin-top: .5rem;
padding-right: .5rem;
}
.callout:not(.callout-captioned) .callout-icon::before {
margin-top: 1rem;
padding-right: .5rem;
}
/* Callout Types */
div.callout-note {
border-left-color: #4582ec !important;
}
div.callout-note .callout-icon::before {
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}
div.callout-note.callout-style-default .callout-caption {
background-color: #dae6fb
}
div.callout-important {
border-left-color: #d9534f !important;
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<section>
<section id="introduction-to-msk-impact-part-2" class="title-slide slide level1 center" data-background-color="#007CBA" style="text-align: center;">
<h1>Introduction to MSK IMPACT Part 2</h1>
<div class="cell">
</div>
<img data-src="images/logos.png" width="1000" class="r-stretch"><p>Karissa Whiting <br> Research Biostatistician <br> Memorial Sloan Kettering <br></p>
<p><br></p>
<p><svg aria-hidden="true" role="img" viewbox="0 0 512 512" style="height:1em;width:1em;vertical-align:-0.125em;margin-left:auto;margin-right:auto;font-size:inherit;fill:white;overflow:visible;position:relative;"><path d="M459.4 151.7c.325 4.548 .325 9.097 .325 13.65 0 138.7-105.6 298.6-298.6 298.6-59.45 0-114.7-17.22-161.1-47.11 8.447 .974 16.57 1.299 25.34 1.299 49.06 0 94.21-16.57 130.3-44.83-46.13-.975-84.79-31.19-98.11-72.77 6.498 .974 12.99 1.624 19.82 1.624 9.421 0 18.84-1.3 27.61-3.573-48.08-9.747-84.14-51.98-84.14-102.1v-1.299c13.97 7.797 30.21 12.67 47.43 13.32-28.26-18.84-46.78-51.01-46.78-87.39 0-19.49 5.197-37.36 14.29-52.95 51.65 63.67 129.3 105.3 216.4 109.8-1.624-7.797-2.599-15.92-2.599-24.04 0-57.83 46.78-104.9 104.9-104.9 30.21 0 57.5 12.67 76.67 33.14 23.72-4.548 46.46-13.32 66.6-25.34-7.798 24.37-24.37 44.83-46.13 57.83 21.12-2.273 41.58-8.122 60.43-16.24-14.29 20.79-32.16 39.31-52.63 54.25z"></path></svg> <span style="color: white"><a href="https://twitter.com/karissawhiting">@karissawhiting</a></span></p>
<p><svg aria-hidden="true" role="img" viewbox="0 0 496 512" style="height:1em;width:0.97em;vertical-align:-0.125em;margin-left:auto;margin-right:auto;font-size:inherit;fill:white;overflow:visible;position:relative;"><path d="M165.9 397.4c0 2-2.3 3.6-5.2 3.6-3.3 .3-5.6-1.3-5.6-3.6 0-2 2.3-3.6 5.2-3.6 3-.3 5.6 1.3 5.6 3.6zm-31.1-4.5c-.7 2 1.3 4.3 4.3 4.9 2.6 1 5.6 0 6.2-2s-1.3-4.3-4.3-5.2c-2.6-.7-5.5 .3-6.2 2.3zm44.2-1.7c-2.9 .7-4.9 2.6-4.6 4.9 .3 2 2.9 3.3 5.9 2.6 2.9-.7 4.9-2.6 4.6-4.6-.3-1.9-3-3.2-5.9-2.9zM244.8 8C106.1 8 0 113.3 0 252c0 110.9 69.8 205.8 169.5 239.2 12.8 2.3 17.3-5.6 17.3-12.1 0-6.2-.3-40.4-.3-61.4 0 0-70 15-84.7-29.8 0 0-11.4-29.1-27.8-36.6 0 0-22.9-15.7 1.6-15.4 0 0 24.9 2 38.6 25.8 21.9 38.6 58.6 27.5 72.9 20.9 2.3-16 8.8-27.1 16-33.7-55.9-6.2-112.3-14.3-112.3-110.5 0-27.5 7.6-41.3 23.6-58.9-2.6-6.5-11.1-33.3 2.6-67.9 20.9-6.5 69 27 69 27 20-5.6 41.5-8.5 62.8-8.5s42.8 2.9 62.8 8.5c0 0 48.1-33.6 69-27 13.7 34.7 5.2 61.4 2.6 67.9 16 17.7 25.8 31.5 25.8 58.9 0 96.5-58.9 104.2-114.8 110.5 9.2 7.9 17 22.9 17 46.4 0 33.7-.3 75.4-.3 83.6 0 6.5 4.6 14.4 17.3 12.1C428.2 457.8 496 362.9 496 252 496 113.3 383.5 8 244.8 8zM97.2 352.9c-1.3 1-1 3.3 .7 5.2 1.6 1.6 3.9 2.3 5.2 1 1.3-1 1-3.3-.7-5.2-1.6-1.6-3.9-2.3-5.2-1zm-10.8-8.1c-.7 1.3 .3 2.9 2.3 3.9 1.6 1 3.6 .7 4.3-.7 .7-1.3-.3-2.9-2.3-3.9-2-.6-3.6-.3-4.3 .7zm32.4 35.6c-1.6 1.3-1 4.3 1.3 6.2 2.3 2.3 5.2 2.6 6.5 1 1.3-1.3 .7-4.3-1.3-6.2-2.2-2.3-5.2-2.6-6.5-1zm-11.4-14.7c-1.6 1-1.6 3.6 0 5.9 1.6 2.3 4.3 3.3 5.6 2.3 1.6-1.3 1.6-3.9 0-6.2-1.4-2.3-4-3.3-5.6-2z"></path></svg> <span style="color: white"><a href="https://github.com/karissawhiting/">github.com/karissawhiting</a></span></p>
</section>
<section id="agenda" class="slide level2">
<h2>Agenda</h2>
<ul>
<li><p><span class="emphasized">Accessing IMPACT Data (Review)</span></p>
<ul>
<li>{cbioportalR}</li>
</ul></li>
<li><p><span class="emphasized">Processing IMPACT Data</span></p>
<ul>
<li>{gnomeR}</li>
</ul></li>
<li><p><span class="emphasized">Visualizing & Analyzing IMPACT Data</span></p>
<ul>
<li>{gnomeR} & {ggplot}</li>
</ul></li>
<li><p><span class="emphasized">Common Analysis Issues</span></p>
<ul>
<li>Multiple testing</li>
<li>Tumor Mutation Burden</li>
<li>Survival Analysis Issues</li>
</ul></li>
</ul>
</section>
<section id="get-the-data-cbioportal" class="slide level2">
<h2>Get the Data: cBioPortal</h2>
<div class="columns">
<div class="column" style="width:60%;">
<ul>
<li class="fragment"><p><span class="emphasized"><strong>cBioPortal</strong></span> is a website and database that provides access to genomic data sets</p></li>
<li class="fragment"><p>Provides tools for <span class="emphasized">downloading, visualizing</span>, and <span class="emphasized">analyzing</span> data sets</p></li>
<li class="fragment"><p>However, we often prefer to do all aspects of analysis programmatically for reproducibility!</p></li>
</ul>
</div><div class="column" style="width:40%;">
<p><img data-src="images/cbp-logo.png"> <img data-src="images/cbp-screenshot.png"></p>
</div>
</div>
</section>
<section id="get-the-data-cbioportalr" class="slide level2">
<h2>Get the Data: cBioPortalR</h2>
<div class="columns">
<div class="column" style="width:70%;">
<p><span class="emphasized">{cbioportalR}</span> allows you to access cBioPortal’s genomic and clinical data sets directly through R</p>
<p>Install the most up to date version:</p>
<div class="sourceCode cell-code" id="cb1"><pre class="sourceCode numberSource r number-lines code-with-copy"><code class="sourceCode r"><span id="cb1-1"><a href="#cb1-1"></a>remotes<span class="sc">::</span><span class="fu">install_github</span>(<span class="st">"karissawhiting/cbioportalR"</span>)</span></code><button title="Copy to Clipboard" class="code-copy-button"><i class="bi"></i></button></pre></div>
<p>Documentation: https://www.karissawhiting.com/cbioportalR/</p>
</div><div class="column">
<p><img data-src="images/cbioportalR-logo.png"></p>
</div>
</div>
</section>
<section id="get-the-data-authenticate-yourself" class="slide level2">
<h2>Get the Data: Authenticate Yourself</h2>
<ul>
<li>You can access public data anytime without credentials using the <span class="emphasized">public site</span> (https://www.cbioportal.org/):</li>
</ul>
<div class="cell">
<div class="sourceCode cell-code" id="cb2"><pre class="sourceCode numberSource r number-lines code-with-copy"><code class="sourceCode r"><span id="cb2-1"><a href="#cb2-1"></a><span class="fu">library</span>(cbioportalR)</span>
<span id="cb2-2"><a href="#cb2-2"></a><span class="fu">set_cbioportal_db</span>(<span class="st">'public'</span>)</span>
<span id="cb2-3"><a href="#cb2-3"></a><span class="fu">available_studies</span>() <span class="sc">%>%</span> <span class="fu">head</span>(<span class="at">n =</span> <span class="dv">3</span>)</span></code><button title="Copy to Clipboard" class="code-copy-button"><i class="bi"></i></button></pre></div>
<div class="cell-output cell-output-stdout">
<pre><code># A tibble: 3 × 13
studyId name descr…¹ publi…² groups status impor…³ allSa…⁴ readP…⁵ cance…⁶
<chr> <chr> <chr> <lgl> <chr> <int> <chr> <int> <lgl> <chr>
1 acc_tcga Adre… "TCGA … TRUE PUBLIC 0 2022-0… 92 TRUE acc
2 bcc_unige… Basa… "Whole… TRUE PUBLIC 0 2022-0… 293 TRUE bcc
3 ampca_bcm… Ampu… "Exome… TRUE PUBLIC 0 2022-0… 160 TRUE ampca
# … with 3 more variables: referenceGenome <chr>, pmid <chr>, citation <chr>,
# and abbreviated variable names ¹description, ²publicStudy, ³importDate,
# ⁴allSampleCount, ⁵readPermission, ⁶cancerTypeId</code></pre>
</div>
</div>
<ul>
<li>Many project rely on <span class="emphasized">internal data sets</span> and will require you to <span class="emphasized">authenticate yourself</span> (https://cbioportal.mskcc.org/)</li>
</ul>
<div class="cell">
<div class="sourceCode cell-code" id="cb4"><pre class="sourceCode numberSource r number-lines code-with-copy"><code class="sourceCode r"><span id="cb4-1"><a href="#cb4-1"></a><span class="co"># assumes you've already gotten a login/token</span></span>
<span id="cb4-2"><a href="#cb4-2"></a><span class="fu">set_cbioportal_db</span>(<span class="st">'msk'</span>)</span>
<span id="cb4-3"><a href="#cb4-3"></a><span class="fu">available_studies</span>() <span class="sc">%>%</span> <span class="fu">head</span>(<span class="at">n =</span> <span class="dv">3</span>)</span></code><button title="Copy to Clipboard" class="code-copy-button"><i class="bi"></i></button></pre></div>
<div class="cell-output cell-output-stdout">
<pre><code># A tibble: 3 × 13
studyId name descr…¹ publi…² pmid citat…³ groups status allSa…⁴ readP…⁵
<chr> <chr> <chr> <lgl> <chr> <chr> <chr> <int> <int> <lgl>
1 dlbc_bcgsc_… Diff… Whole … TRUE 2369… Morin … PUBLIC 1 52 TRUE
2 dlbc_broad Diff… Whole … TRUE 2234… Lohr e… PUBLIC 1 58 TRUE
3 fl_unmc Foll… Copy-n… TRUE <NA> <NA> EXTEN… 1 198 TRUE
# … with 3 more variables: cancerTypeId <chr>, referenceGenome <chr>,
# importDate <chr>, and abbreviated variable names ¹description,
# ²publicStudy, ³citation, ⁴allSampleCount, ⁵readPermission</code></pre>
</div>
</div>
</section>
<section id="get-the-data-how-data-is-organized-in-cbioportal" class="slide level2">
<h2>Get the Data: How Data is Organized in cBioPortal</h2>
<img data-src="images/cbp-diagram.png" class="r-stretch"></section>
<section id="get-the-data-how-data-is-organized-in-cbioportal-1" class="slide level2">
<h2>Get the Data: How Data is Organized in cBioPortal</h2>
<p><span class="emphasized">!! NOTE: Some studies exist in both public and MSK databases, but may differ in format or content</span></p>
<img data-src="images/cbp-diagram.png" class="r-stretch"></section>
<section id="get-the-data-a-few-notes" class="slide level2">
<h2>Get the Data: A Few Notes</h2>
<ul>
<li><p>Sometimes you need to analyze <span class="emphasized">data not available in cBioPortal</span> in cases of:</p>
<ul>
<li>Germline tumor samples</li>
<li>Samples from other institutions</li>
<li>Data hand curated/annotated for certains variants (e.g. certain SNPs only)</li>
</ul></li>
<li><p>Be sure to check for <span class="emphasized">selection of genes</span> or filters that may have been applied</p></li>
<li><p>You may have to do some additional data wrangling to get this data to work in MSK pipelines</p></li>
</ul>
</section></section>
<section>
<section id="processing-data" class="title-slide slide level1 center" data-background-color="#007CBA" style="text-align: center;">
<h1>Processing Data</h1>
</section>
<section id="processing-data-issues-to-address" class="slide level2">
<h2>Processing Data: Issues To Address</h2>
<ol type="1">
<li><strong>Research Samples vs. IMPACT Samples</strong>
<ul>
<li>Some samples may be sequenced outside MSK or using different panels. You can usually tell by the sample ID (if P-000XXX-T0X-IMX, it is likely IMPACT with IMX indicating panel)</li>
</ul></li>
<li><strong>Cohort Inclusion</strong>
<ul>
<li>Samples with no alterations may be dropped when pulling data</li>
</ul></li>
<li><strong>Data Formats & Gene Standards Often Inconsistent</strong>
<ul>
<li>Column names, data formats and gene names may differ between studies or even within studies!</li>
</ul></li>
<li><strong>Missing Data in Mutation Status</strong>
<ul>
<li>Mutation Status is sometimes missing data.</li>
</ul></li>
</ol>
</section>
<section id="processing-data-code-example" class="slide level2">
<h2>Processing Data: Code Example</h2>
<p><span class="largest">Code Example on github:</span> <span class="larger"><a href="https://github.com/MSKCC-Epi-Bio/introduction-to-msk-impact">https://github.com/MSKCC-Epi-Bio/introduction-to-msk-impact</a></span></p>
</section>
<section id="processing-data-recap" class="slide level2">
<h2>Processing Data: Recap</h2>
<ol type="1">
<li><strong>Research Samples vs. IMPACT Samples</strong>
<ul>
<li>Some samples may be sequenced outside MSK or using different panels.</li>
<li><span class="emphasized">Check panels and annotate NAs accordingly</span></li>
</ul></li>
<li><strong>Cohort Inclusion</strong>
<ul>
<li>Samples with no alterations may be dropped when pulling data</li>
<li><span class="emphasized">Use <code>samples</code> arg of <code>create_gene_binary()</code> and check data</span></li>
</ul></li>
<li><strong>Data Formats & Gene Standards Often Inconsistent</strong>
<ul>
<li>Column names, data formats and gene names may differ between studies or even within studies!</li>
<li><span class="emphasized">Reformat data as necessary and check gene aliases (<code>recode_aliases = TRUE</code>)</span></li>
</ul></li>
<li><strong>Missing Data in Mutation Status</strong>
<ul>
<li>Mutation Status is sometimes missing data.</li>
<li><span class="emphasized">Check Mutation Status column</span></li>
</ul></li>
</ol>
</section></section>
<section>
<section id="analyzing-data" class="title-slide slide level1 center" data-background-color="#007CBA" style="text-align: center;">
<h1>Analyzing Data</h1>
</section>
<section id="analyzing-data-issues-to-address" class="slide level2">
<h2>Analyzing Data: Issues To Address</h2>
<ol type="1">
<li><strong>OncoKB Annotation</strong>
<ul>
<li>Some studies may require oncoKB annotation of data</li>
</ul></li>
<li><strong>Multiple Testing and False Positives</strong>
<ul>
<li>Very low prevalence genes are often not very informative in standard IMPACT analyses. Choose a threshold (e.g. 1% or 5 %) <em>a prior</em> to limit number of tests.</li>
<li>Report q-value (adjusted for multiple testing)</li>
</ul></li>
<li><strong>Analyzing Tumor Mutation Burden Across Samples</strong>
<ul>
<li>Although TMB is always measured as number of mutations per coding area, depth of sequencing can make this measure inconsistent between studies.</li>
<li>Usually ok within IMPACT studies but not always comparable with WES studies</li>
</ul></li>
<li><strong>Survival Analysis Biases</strong></li>
</ol>
</section>
<section id="analyzing-data-multiple-testing" class="slide level2">
<h2>Analyzing Data: Multiple Testing</h2>
<ul>
<li><p>Because each hypothesis test has a probability of producing a type I error (falsely rejecting a null hypothesis that is true), performing a large number of hypothesis tests virtually guarantees the presence of type I errors among the findings.</p></li>
<li><p>Firstly, depending on size of data and type of analysis, choose a prevalence threshold for genes to test</p></li>
<li><p><span class="emphasized">Report tests with adjustment</span>- Recommended to use false discovery rate adjustment as opposed to FWER (eg. bonferroni) as it controls for a low proportion of false positives, instead of guarding against making any false positive conclusion at all</p></li>
<li><p>Reference: Goeman JJ, Solari A. Multiple hypothesis testing in genomics. Stat Med. 2014 May 20;33(11):1946-78. doi: 10.1002/sim.6082. Epub 2014 Jan 8. PMID: 24399688.</p></li>
</ul>
</section>
<section id="analyzing-data-tumor-mutational-burden" class="slide level2">
<h2>Analyzing Data: Tumor Mutational Burden</h2>
<ul>
<li>Tumor mutation burden (TMB): total number of mutations per coding area of a tumor genome.</li>
<li>Coding area (denominator) different for different versions of MSK-IMPACT</li>
</ul>
<img data-src="images/tmb.png" class="r-stretch"><ul>
<li>Get this data from cBioPortal when you can (they have published methods on this).</li>
</ul>
<div class="sourceCode cell-code" id="cb6"><pre class="sourceCode numberSource r number-lines code-with-copy"><code class="sourceCode r"><span id="cb6-1"><a href="#cb6-1"></a><span class="fu">available_clinical_attributes</span>(<span class="sc"><</span>your<span class="sc">-</span>study<span class="sc">></span>)</span>
<span id="cb6-2"><a href="#cb6-2"></a><span class="fu">get_clinical_by_study</span>(<span class="at">clinical_attribute =</span> <span class="sc"><</span>tmb<span class="sc">-</span>attribute<span class="sc">-</span>name<span class="sc">></span>)</span></code><button title="Copy to Clipboard" class="code-copy-button"><i class="bi"></i></button></pre></div>
<ul>
<li>If it’s not available, you can calculate it yourself</li>
</ul>
</section>
<section id="analyzing-data-survival-analysis-biases" class="slide level2">
<h2>Analyzing Data: Survival Analysis Biases</h2>
<ul>
<li>Often in older studies, patients who were sampled were worse off- check this if you can</li>
<li>Also, sampling bias may be present:</li>
</ul>
<p><span class="larger">Brown S, Lavery JA, Shen R, et al. Implications of Selection Bias Due to Delayed Study Entry in Clinical Genomic Studies. JAMA Oncol. 2022;8(2):287–291. doi:10.1001/jamaoncol.2021.5153</span></p>
</section></section>
<section id="thank-you" class="title-slide slide level1 center" data-background-color="#007CBA" style="text-align: center;">
<h1>Thank You!</h1>
<div class="footer footer-default">
</div>
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