06d7be056190c14b85e71bc12523f18ea6815b5e markd Mon Dec 7 00:50:29 2020 -0800 BLAT mmap index support merge with master diff --git src/hg/makeDb/trackDb/human/covidMuts.html src/hg/makeDb/trackDb/human/covidMuts.html new file mode 100644 index 0000000..d47d628 --- /dev/null +++ src/hg/makeDb/trackDb/human/covidMuts.html @@ -0,0 +1,133 @@ +<h2>Description</h2> +<p> +This track shows rare variants associated with monogenic congenital defects of immunity to +the <b>SARS-CoV-2</b> virus identified by the +<a target=_blank href="https://www.covidhge.com/">COVID Human Genetic Effort</a>. +This international consortium aims to discover truly causative variations: those underlying +severe forms of COVID-19 in previously healthy individuals, and those that make certain +individuals resistant to infection by the SARS-CoV2 virus despite repeated exposure. +</p> +<p> +The major feature of the small set of variants in this track is that they are functionally tested +to be <b>deleterious</b> and genetically tested to be <b>disease-causing</b>. +Specifically, rare variants were predicted to be loss-of-function at human loci known to govern +interferon (IFN) immunity to influenza virus in patients with life-threatening COVID-19 pneumonia, +relative to subjects with asymptomatic or benign infection. +These genetic defects display incomplete penetrance for influenza respiratory distress and only +appear clinically upon infection with the more virulent SARS-CoV-2. +</p> + +<h2>Display Conventions</h2> +<p> +Only eight genes and few variants are contained in this track. Use the links in the table to +browse the gene of interest: +</p> + +<table class="stdTbl"> + <tr> + <th>Gene Name</th> + <th>Human GRCh37/hg19 Assembly</th> + <th>Human GRCh38/hg38 Assembly</th> + </tr> + <tr> + <td>TLR3</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr4:186990309-187006252"> +chr4:186990309-187006252</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr4:186069152-186088069"> +chr4:186069152-186088069</a></td> + </tr> + <tr> + <td>IRF7</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr11:612555-615999"> +chr11:612555-615999</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr11:612591-615970"> +chr11:612591-615970</a></td> + </tr> + <tr> + <td>UNC93B1</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr11:67758575-67771593"> +chr11:67758575-67771593</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr11:67991100-68004097"> +chr11:67991100-68004097</a></td> + </tr> + <tr> + <td>TBK1</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr12:64845840-64895899"> +chr12:64845840-64895899</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr12:64452120-64502114"> +chr12:64452120-64502114</a></td> + </tr> + <tr> + <td>TICAM1</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr19:4815936-4831754"> +chr19:4815936-4831754</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr19:4815932-4831704"> +chr19:4815932-4831704</a></td> + </tr> + <tr> + <td>IRF3</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr19:50162826-50169132"> +chr19:50162826-50169132</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr19:49659570-49665875"> +chr19:49659570-49665875</a></td> + </tr> + <tr> + <td>IFNAR1</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr21:34697214-34732128"> +chr21:34697214-34732128</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr21:33324970-33359864"> +chr21:33324970-33359864</a></td> + </tr> + <tr> + <td>IFNAR2</td> + <td><a href="../cgi-bin/hgTracks?db=hg19&covidMuts=pack&position=chr21:34602231-34636820"> +chr21:34602231-34636820</a></td> + <td><a href="../cgi-bin/hgTracks?db=hg38&covidMuts=pack&position=chr21:33229974-33264525"> +chr21:33229974-33264525</a></td> + </tr> +</table> + +<h2>Methods</h2> +<p> +This track uses variant calls in autosomal IFN-related genes from whole exome and genome data +with a MAF lower than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function. +The patient population studied consisted of 659 patients with life-threatening COVID-19 pneumonia +relative to 534 subjects with asymptomatic or benign infection of varying ethnicities. +Variants underlying autosomal-recessive or autosomal-dominant deficiencies were identified in +23 patients (3.5%) 17 to 77 years of age. +The proportion of individuals carrying at least one variant was compared between severe cases +and control cases by means of logistic regression with the likelihood ratio test. +Principal Component Analysis (PCA) was conducted with Plink v1.9 software on whole exome and +genome sequencing data with the 1000 Genomes (1kG) Project phase 3 public database as reference. +Analysis of enrichment in rare synonymous variants of the genes was performed to check the +calibration of the burden test. +The odds ratio was also estimated by logistic regression and adjusted for ethnic heterogeneity. +</p> + +<h2>Data Access</h2> +<p> +The raw data can be explored interactively with the <a target="_blank" href="../cgi-bin/hgTables"> +Table Browser</a>, or the <a target="_blank" href="../cgi-bin/hgIntegrator">Data Integrator</a>. +Please refer to +our <a href="https://groups.google.com/a/soe.ucsc.edu/forum/#!forum/genome" +target="_blank">mailing list archives</a> for questions, or our <a target="_blank" +href="../FAQ/FAQdownloads.html#download36">Data Access FAQ</a> for more information. +</p> + +<h2>Credits</h2> +<p> +Thanks to the COVID Human Genetic Effort contributors for making these data available, and in +particular to Qian Zhang at the Rockefeller University for review and input during browser track +development. +</p> + +<h2>References</h2> +<p> +Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C +<em>et al</em>. +<a href="https://www.ncbi.nlm.nih.gov/pubmed/32972995" target="_blank"> +Inborn errors of type I IFN immunity in patients with life-threatening COVID-19</a>. +<em>Science</em>. 2020 Sep 24;. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/32972995" target="_blank">32972995</a> +</p> +