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 @@ -1,32 +1,32 @@ <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> @@ -77,42 +77,43 @@ 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