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Cloufield committed Jun 14, 2024
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18 changes: 11 additions & 7 deletions 09_Gene_based_analysis/index.html
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Expand Up @@ -2312,7 +2312,11 @@ <h2 id="table-of-contents">Table of Contents</h2>
<li><a href="#reference">Reference</a></li>
</ul>
<h3 id="magma-introduction">MAGMA Introduction</h3>
<p>MAGMA is one the most commonly used tools for gene-based and gene-set analysis. </p>
<p>MAGMA is one of the most commonly used tools for gene-based and gene-set analysis. </p>
<div class="admonition info">
<p class="admonition-title">Overview of MAGMA</p>
<p><img width="700" alt="image" src="https://github.com/Cloufield/GWASTutorial/assets/40289485/3b0c887b-ead4-4146-ad01-c3693b9cff2f"></p>
</div>
<p><strong>Gene-level analysis</strong> in MAGMA uses two models:</p>
<p><strong>1.Multiple linear principal components regression</strong></p>
<p>MAGMA employs a multiple linear principal components regression, and F test to obtain P values for genes.
Expand All @@ -2326,7 +2330,7 @@ <h3 id="magma-introduction">MAGMA Introduction</h3>
<li><span class="arithmatex">\(W\)</span> : covariate matrix</li>
<li><span class="arithmatex">\(\beta_g\)</span> : effects of covariates </li>
</ul>
<p><span class="arithmatex">\(X_g\)</span> is obtained by first projecting the variant matrix of a gene onto its PC, and removing PCs with samll eigenvalues.</p>
<p><span class="arithmatex">\(X_g\)</span> is obtained by first projecting the variant matrix of a gene onto its PC, and removing PCs with small eigenvalues.</p>
<div class="admonition note">
<p class="admonition-title">Note</p>
<p>The linear principal components regression model requires raw genotype data.</p>
Expand All @@ -2348,10 +2352,10 @@ <h3 id="magma-introduction">MAGMA Introduction</h3>
\]</div>
<ul>
<li><span class="arithmatex">\(S_S\)</span> : indicator (if the gene is in a specified gene set)</li>
<li><span class="arithmatex">\(\beta_S\)</span> : difference in effects between genes in the specified set and genes ouside the set.</li>
<li><span class="arithmatex">\(\beta_S\)</span> : difference in effects between genes in the specified set and genes outside the set.</li>
</ul>
<h3 id="install-magma">Install MAGMA</h3>
<p>Dowload MAGMA for your operating system from the following url:</p>
<p>Download MAGMA for your operating system from the following URL:</p>
<p>MAGMA: https://ctg.cncr.nl/software/magma</p>
<p>For example:
<div class="highlight"><pre><span></span><code>cd ~/tools
Expand All @@ -2366,15 +2370,15 @@ <h3 id="install-magma">Install MAGMA</h3>
MAGMA version: v1.10 (linux)
</code></pre></div></p>
<h3 id="download-reference-files">Download reference files</h3>
<p>We nedd the following reference files:</p>
<p>We need the following reference files:</p>
<ul>
<li>gene location files</li>
<li>LD reference panel</li>
<li>Gene-set files</li>
</ul>
<p>The gene location files and LD reference panel can be downloaded from magma website. </p>
<p>-&gt; https://ctg.cncr.nl/software/magma</p>
<p>The third one can be downloaded form MsigDB. </p>
<p>The third one can be downloaded from MsigDB. </p>
<p>-&gt; https://www.gsea-msigdb.org/gsea/msigdb/</p>
<h3 id="format-input-files">Format input files</h3>
<div class="highlight"><pre><span></span><code>zcat ../08_LDSC/BBJ_HDLC.txt.gz | awk &#39;NR&gt;1 &amp;&amp; $2==3 {print $1,$2,$3}&#39; &gt; HDLC_chr3.magma.input.snp.chr.pos.txt
Expand All @@ -2390,7 +2394,7 @@ <h3 id="annotate-snps">Annotate SNPs</h3>
</code></pre></div>
<div class="admonition tip">
<p class="admonition-title">Tip</p>
<p>Usually to capture the variants in the regulatory regions, we will add windows upstream and downstream of the genes with <code>--annotate window</code>. </p>
<p>Usually, to capture the variants in the regulatory regions, we will add windows upstream and downstream of the genes with <code>--annotate window</code>. </p>
<p>For example, <code>--annotate window=35,10</code> set a 35 kilobase pair(kb) upstream and 10kb downstream window.</p>
</div>
<h3 id="gene-based-analysis">Gene-based analysis</h3>
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