Description

This track is part of the Episignatures collection.

It shows the individual CpG sites that make up the DNA methylation signatures 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.

Display Conventions and Configuration

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 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.

Hovering over a CpG displays:

• The episignature driving the displayed color (highest absolute delta-beta).
• The methylation direction (Gain or Loss).
• The corresponding delta-beta value.

Example (cg16689481):

NSD1|Gain|0.318

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.

Four filters are available on the track configuration page. The Episignature filter keeps only sites that are part of all of the selected episignatures, which is the way to find the CpGs that two or more disorders have in common. The others keep a site by the Number of episignatures at this probe, the Direction of methylation change, and the Absolute delta-beta of the strongest episignature at this probe.

Included episignatures

The 24 episignatures in the track, with the number of CpG sites each contributes and the study that published it. Two signatures are listed for Kabuki syndrome, from a 2017 and a 2026 study, and they are kept apart rather than merged.

Episignature	Disorder	OMIM	CpG probes	Reference
16pDel	Autism spectrum	611913	106	Siu 2019
ANKRD11	KBG syndrome	148050	82	Awamleh 2023
ARID1B	Coffin-Siris syndrome 1	135900	142	Chen 2026
ASXL1	Bohring-Opitz syndrome	605039	695	Awamleh 2022
CHD7	CHARGE syndrome	214800	151	Butcher 2017
CHD8	Intellectual developmental disorder with autism and macrocephaly	615032	389	Siu 2019
Dup7	Chromosome 7q11.23 duplication syndrome	609757	405	Strong 2015
DYRK1A	Intellectual developmental disorder, autosomal dominant 7	614104	383	Courraud 2021
EHMT1	Kleefstra syndrome 1	610253	535	Goodman 2020
EZH2	Weaver syndrome	277590	213	Choufani 2020
FHS	Floating-Harbor syndrome	136140	415	Rots 2021
HNRNPK	Au-Kline syndrome	616580	388	Choufani 2022
KANSL1	Koolen-De Vries syndrome	610443	424	Awamleh 2024
KMT2A	Wiedemann-Steiner syndrome	605130	240	Awamleh 2026
KMT2B	Dystonia 28, childhood-onset	617284	4286	Awamleh 2026
KMT2C	Kleefstra syndrome 2	617768	37	Rots 2024
KMT2D_2017	Kabuki syndrome 1	147920	196	Butcher 2017
KMT2D_2026	Kabuki syndrome 1	147920	632	Wang 2026
MN1	CEBALID syndrome	618774	27	Mak 2025
NSD1	Sotos syndrome	117550	6359	Choufani 2015
SMARCA2	Nicolaides-Baraitser syndrome	601358	404	Chater-Diehl 2019
SRCAP	Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities	619595	314	Rots 2021
T21	Down syndrome	190685	782	Reko 2026
Williams	Williams-Beuren syndrome	194050	1198	Strong 2015

Methods

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 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. 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.

Data Access

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.

Credits

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.

References

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