b0f7c3b8ed633f460990b271070d2c72a4d05ba1 jnavarr5 Fri Sep 25 14:55:45 2026 -0700 Adding GitHub links for the makedoc, scripts, and trackDb to the EpigenCentral page, crediting Max, adding the Turinsky DOI, and using serial commas, refs #38112 diff --git src/hg/makeDb/trackDb/human/hg38/epigenCentral.html src/hg/makeDb/trackDb/human/hg38/epigenCentral.html index 38afcd2ae9c..a54bdabdf9c 100644 --- src/hg/makeDb/trackDb/human/hg38/epigenCentral.html +++ src/hg/makeDb/trackDb/human/hg38/epigenCentral.html @@ -11,57 +11,57 @@ Centre for Computational Medicine and the Weksberg lab at the Hospital for Sick Children in Toronto where a user can upload a methylation array sample and have it classified against those signatures. The track covers 15,035 CpG sites drawn from 24 episignatures for 23 rare disorders. Every site is one that was found to be differentially methylated between affected individuals and controls in the study that published the signature. A site is often part of the signature of more than one disorder, so one row is shown per site and all the episignatures that report it are listed together on that row. </p> <h2>Display Conventions and Configuration</h2> <p> Each CpG site is drawn as a single-base feature, colored by the direction of the methylation change. Delta-beta is the mean methylation in cases minus the mean methylation in controls, so a positive value is a gain of methylation in cases and a negative value is a loss. Where a site -belongs to several episignatures, the color, the mouse-over and the delta-beta shown come from +belongs to several episignatures, the color, the mouse-over, and the delta-beta shown come from the episignature with the largest absolute delta-beta at that site. </p> <table class="stdTbl"> <tr><th style="background-color:#FF5F01;width:2em"> </th> <td>Gain of methylation in cases, positive delta-beta</td></tr> <tr><th style="background-color:#0072EB;width:2em"> </th> <td>Loss of methylation in cases, negative delta-beta</td></tr> </table> <p> The <b>Direction of methylation change</b> filter uses the same strongest episignature, so it does not catch a site where a weaker episignature changes in the opposite direction; about 1,600 of the 2,850 sites with more than one episignature are of this kind. The table on the details page lists every episignature at the site with its own direction. </p> <p> The mouse-over gives the probe ID, how many episignatures cover the site, and the episignature -with the largest effect there with its disorder, direction and delta-beta. +with the largest effect there with its disorder, direction, and delta-beta. </p> <p> Clicking a site opens a page with a table of every episignature at that site, one row each, giving the gene or locus, the disorder, its OMIM entry, the direction, the delta-beta, the -adjusted p-value and the multiple-testing correction that the publishing study used. Studies +adjusted p-value, and the multiple-testing correction that the publishing study used. Studies differ in which correction they applied, so the adjusted p-values in one row are not always directly comparable with those in another. </p> <p> Three filters are available on the track configuration page. The episignature filter keeps only sites that are part of <em>all</em> of the selected episignatures, which is the way to find the CpGs that two or more disorders have in common. The other two keep a site by how many episignatures cover it and by the direction and size of the strongest change at it. </p> <h2>Included episignatures</h2> <p> The 24 episignatures in the track, with the number of CpG sites each contributes and the study @@ -94,76 +94,79 @@ <tr><td>NSD1</td><td>Sotos syndrome</td><td><a href="https://omim.org/entry/117550" target="_blank">117550</a></td><td>6359</td><td><a href="https://pubmed.ncbi.nlm.nih.gov/26690673/" target="_blank">Choufani 2015</a></td></tr> <tr><td>SMARCA2</td><td>Nicolaides-Baraitser syndrome</td><td><a href="https://omim.org/entry/601358" target="_blank">601358</a></td><td>404</td><td><a href="https://pubmed.ncbi.nlm.nih.gov/31288860/" target="_blank">Chater-Diehl 2019</a></td></tr> <tr><td>SRCAP</td><td>Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities</td><td><a href="https://omim.org/entry/619595" target="_blank">619595</a></td><td>314</td><td><a href="https://pubmed.ncbi.nlm.nih.gov/33909990/" target="_blank">Rots 2021</a></td></tr> <tr><td>T21</td><td>Down syndrome</td><td><a href="https://omim.org/entry/190685" target="_blank">190685</a></td><td>782</td><td><a href="https://pubmed.ncbi.nlm.nih.gov/42492524/" target="_blank">Reko 2026</a></td></tr> <tr><td>Williams</td><td>Williams-Beuren syndrome</td><td><a href="https://omim.org/entry/194050" target="_blank">194050</a></td><td>1198</td><td><a href="https://pubmed.ncbi.nlm.nih.gov/26166478/" target="_blank">Strong 2015</a></td></tr> </table> <!-- END generated --> <h2>Methods</h2> <p> Each episignature was established by comparing genome-wide DNA methylation, measured on Illumina methylation arrays in blood, between a group of individuals carrying pathogenic variants in the gene or locus concerned and a control group, and keeping the CpG probes whose case-control difference survived correction for multiple testing. The studies behind the individual -signatures are listed in the table above and differ in cohort size, array version and +signatures are listed in the table above and differ in cohort size, array version, and statistical treatment; EpigenCentral collects their published probe lists, adds the disorder and OMIM annotation, and serves them together. The portal and the classification it offers are -described in Turinsky et al. +described in Turinsky <em>et al.</em> </p> <p> The data came from the track hub that the EpigenCentral group publishes at <a href="https://github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser" target="_blank">github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser</a>, whose <tt>episignatures.bb</tt> file already carries the probe coordinates on hg38. Bringing it in as a track hosted here changed four things and no coordinates or values: the OMIM column was reduced from a full URL to the entry number so the browser can build the link itself; a pre-rendered mouse-over column was replaced by the direction alone, with the mouse-over text assembled from the fields instead; the disorder of the strongest episignature was added as its own column; and 215 rows repeated within the per-site comparison table, affecting 137 sites, were removed, since the site's own count of episignatures already counted each one once. As a check on the coordinates, 5,000 sampled sites all fall on a CG dinucleotide in the hg38 sequence, and all 14,236 probes the track shares with the MethaDory track are at the same position in both. One entry, the Dup7 signature at cg19457237, has no direction or delta-beta in the source data -and is shown as NA. The commands are in the -<a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/episignatures.txt" target="_blank">makeDoc</a> -and the scripts in -<a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/episignatures" target="_blank">src/hg/makeDb/scripts/episignatures</a>. +and is shown as NA. The commands are in the makedoc, +<a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/episignatures.txt" target="_blank">doc/hg38/episignatures.txt</a>, +the scripts in +<a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/episignatures" target="_blank">makeDb/scripts/episignatures</a>, +and the track settings in +<a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/trackDb/human/hg38/episignatures.ra" target="_blank">trackDb/human/hg38/episignatures.ra</a>. </p> <h2>Data Access</h2> <p> At the request of the data providers this track is not available through the <a href="../cgi-bin/hgTables">Table Browser</a>, the -<a href="../cgi-bin/hgIntegrator">Data Integrator</a> or the +<a href="../cgi-bin/hgIntegrator">Data Integrator</a>, or the <a href="https://api.genome.ucsc.edu" target="_blank">REST API</a>. Please obtain the data from EpigenCentral instead, either from the portal at <a href="https://epigen.ccm.sickkids.ca/" target="_blank">epigen.ccm.sickkids.ca</a> or from the track hub repository at <a href="https://github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser" target="_blank">github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser</a>, where the same annotation is distributed as a bigBed file. The file can be read with our tool <tt>bigBedToBed</tt>, which can be compiled from the source code or downloaded as a precompiled binary for your system; instructions for downloading source code and binaries can be found -<a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads" target="_blank">here</a>. +<a href="https://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads" target="_blank">here</a>. </p> <h2>Credits</h2> <p> Thanks to Prajkta Kallurkar and the Centre for Computational Medicine, and to the Weksberg lab at the Hospital for Sick Children in Toronto, for curating the episignatures and for building the track hub this track is based on. Thanks also to the groups whose published episignatures are collected here, listed in the table above. The track was brought to the Genome Browser by Eliza -Alde, Barali Kitiyakara and Jairo Navarro. +Alde, Barali Kitiyakara, Max Haeussler, and Jairo Navarro. </p> <h2>References</h2> <p> Turinsky AL, Choufani S, Lu K, Liu D, Mashouri P, Min D, Weksberg R, Brudno M. <a href="https://www.ncbi.nlm.nih.gov/pubmed/32623772" target="_blank"> EpigenCentral: Portal for DNA methylation data analysis and classification in rare diseases</a>. <em>Hum Mutat</em>. 2020 Oct;41(10):1722-1733. +DOI: <a href="https://doi.org/10.1002/humu.24076" target="_blank">10.1002/humu.24076</a>; PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/32623772" target="_blank">32623772</a> </p>