622e9ba577122e4b2c61504ca2f92a2f75d93c8e kate Tue Nov 10 16:14:24 2020 -0800 Polishing description and methods sections of track description, with Ana. refs 326351 diff --git src/hg/makeDb/trackDb/human/covidMuts.html src/hg/makeDb/trackDb/human/covidMuts.html index fbf2275..fe051f7 100644 --- src/hg/makeDb/trackDb/human/covidMuts.html +++ src/hg/makeDb/trackDb/human/covidMuts.html @@ -1,132 +1,133 @@ <h2>Description</h2> <p> -This track shows 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 detect rare or common monogenic inborn immunity errors (IEI) underlying severe forms of COVID-19 -in previously healthy individuals, as well as rare or common monogenic variations that make certain -individuals resistant to infection by SARS-CoV2 virus despite repeated exposure. +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 (LOF) at 13 human loci known to govern -TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus in patients with -life-threatening COVID-19 pneumonia, relative to subjects with asymptomatic or benign infection. +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 -manifested clinically upon infection with the more virulent SARS-CoV-2. +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&covidHgeMuts=pack&position=chr4:186990309-187006252"> chr4:186990309-187006252</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr4:186069152-186088069"> chr4:186069152-186088069</a></td> </tr> <tr> <td>IRF7</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr11:612555-615999"> chr11:612555-615999</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr11:612591-615970"> chr11:612591-615970</a></td> </tr> <tr> <td>UNC93B1</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr11:67758575-67771593"> chr11:67758575-67771593</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr11:67991100-68004097"> chr11:67991100-68004097</a></td> </tr> <tr> <td>TBK1</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr12:64845840-64895899"> chr12:64845840-64895899</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr12:64452120-64502114"> chr12:64452120-64502114</a></td> </tr> <tr> <td>TICAM1</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr19:4815936-4831754"> chr19:4815936-4831754</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr19:4815932-4831704"> chr19:4815932-4831704</a></td> </tr> <tr> <td>IRF3</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr19:50162826-50169132"> chr19:50162826-50169132</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr19:49659570-49665875"> chr19:49659570-49665875</a></td> </tr> <tr> <td>IFNAR1</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr21:34697214-34732128"> chr21:34697214-34732128</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr21:33324970-33359864"> chr21:33324970-33359864</a></td> </tr> <tr> <td>IFNAR2</td> <td><a href="../cgi-bin/hgTracks?db=hg19&covidHgeMuts=pack&position=chr21:34602231-34636820"> chr21:34602231-34636820</a></td> <td><a href="../cgi-bin/hgTracks?db=hg38&covidHgeMuts=pack&position=chr21:33229974-33264525"> chr21:33229974-33264525</a></td> </tr> </table> <h2>Methods</h2> <p> -Variant calls in 12 autosomal IFN-related genes from whole exome or genome data with a MAF lower -than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function (LOF) were considered -for statistical analysis. The proportion of individuals carrying at least one pLOF variant was -compared between cases and controls by means of logistic regression with the likelihood ratio test. -The first three principal components of the PCA were included in the logistic regression model -to account for ethnic heterogeneity of the cohorts. -Analysis of enrichment in rare (MAF < 0.001) synonymous -variants of the 12 genes was performed to check the calibration of the burden test. PCA was -conducted with Plink v1.9 software on whole exome and genome sequencing data and 1000 Genomes (1kG) -Project phase 3 public database as reference, using 27,480 exonic variants with a minor allele -frequency >0.01 and a call rate >0.99. The odds ratio was also estimated by logistic regression -and adjusted for ethnic heterogeneity. +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>