This track is part of the Episignatures collection.
-It shows the individual CpG sites that make up the DNA methylation episignatures curated by +It shows the individual CpG sites that make up the DNA methylation episignatures available on EpigenCentral, a portal from the 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.
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 the episignature with the largest absolute delta-beta at that site.
| Gain of methylation in cases, positive delta-beta | |
| Loss of methylation in cases, negative delta-beta |
-The Direction of methylation change 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. +The Direction of methylation change filter uses the episignature with the largest absolute +delta-beta value at a site. As a result, when multiple episignatures share a CpG and report +different directions of methylation change, the filter reflects only the direction associated with +the largest absolute delta-beta value. The table on the details page lists every episignature at +the site with its own direction.
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.
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 differ in which correction they applied, so the adjusted p-values in one row are not always directly comparable with those in another.
@@ -97,78 +98,78 @@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 -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 +statistical treatment; EpigenCentral uses these published DNA methylation signatures to develop +classification models that enable users to compare their own methylation data against established +episignatures. The portal and the classification it offers are described in Turinsky et al.
The data came from the track hub that the EpigenCentral group publishes at github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser, whose episignatures.bb 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 makedoc, +The commands are in the makedoc, doc/hg38/episignatures.txt, the scripts in makeDb/scripts/episignatures, and the track settings in trackDb/human/hg38/episignatures.ra.
At the request of the data providers this track is not available through the Table Browser, the Data Integrator, or the REST API. Please obtain the data from EpigenCentral instead, either from the portal at epigen.ccm.sickkids.ca or from the track hub repository at github.com/ccmbioinfo/EpigenCentral-UCSC-Genome-Browser, where the same annotation is distributed as a bigBed file. The file can be read with our tool bigBedToBed, 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 here.
-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 +Thanks to the Center for Computational Medicine and the Weksberg lab at the Hospital for Sick +Children (SickKids) 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, Max Haeussler, and Jairo Navarro.
Turinsky AL, Choufani S, Lu K, Liu D, Mashouri P, Min D, Weksberg R, Brudno M. EpigenCentral: Portal for DNA methylation data analysis and classification in rare diseases. Hum Mutat. 2020 Oct;41(10):1722-1733. DOI: 10.1002/humu.24076; PMID: 32623772