c248c85dafaa2167b3ad8e0ad76be7d4a9a05385 max Fri Oct 30 09:02:47 2020 -0700 lifting covid rare mutations to hg38 and polishing up the track a bit more, refs #26351 diff --git src/hg/makeDb/trackDb/human/covidMuts.html src/hg/makeDb/trackDb/human/covidMuts.html new file mode 100644 index 0000000..303b490 --- /dev/null +++ src/hg/makeDb/trackDb/human/covidMuts.html @@ -0,0 +1,82 @@ +<h2>Description</h2> +<p> +This track shows variants associated with monogenic congenital defects of immunity to <b>SARS-CoV-2</b>, +with incomplete or complete penetrance from 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. +</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. +These genetic defects display incomplete penetrance for influenza respiratory distress and only +manifested clinically upon infection with the more virulent SARS-CoV-2. +</p> + +<h2>Display Conventions</h2> +<p> +Unlike a regular genome browser track, the <b>COVID-19 Immunity Variants</b> track displays all +affected genes in <a href="https://genome.ucsc.edu/goldenPath/help/multiRegionHelp.html">multi-region view</a>, +showing the variants within the coordinates of the gene, but hiding all the intergenic bases. To +return to the default Genome Browser view, click on the "-" button next to the "region" box. +</p> +<p> +Only eight genes and few variants are contained in this track. Use the links below to browse the +the gene of interest: + +<dl> + <dd>Gene 1 chr:</dd> + <dd>Gene 2 chr:</dd> +</dl> +</p> + +<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. +</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> + +