+Part of the Imprinting track collection, these tracks show an atlas of allele-specific +methylation built from deep whole-genome bisulfite sequencing of 202 purified samples covering +about 40 human cell types from 135 donors. +Because the sequencing was deep and the reads long enough to cover several CpG sites at once, the +authors could look at one DNA fragment at a time and ask whether a region carried two distinct +methylation states rather than one intermediate average. Regions that do are called bimodal here. +Where a nearby heterozygous SNP is available, the two states can be assigned to the two copies of +the chromosome, which separates the cases where methylation follows the DNA sequence from the much +rarer cases where it follows the parent the copy came from. +
+ ++The collection has three annotation sets: +
+ ++The authors published these annotations for hg19 only. Everything here was lifted to hg38, so +positions should be treated with the usual care given to lifted data. See Methods for what was +lost or changed in the lift. +
+ ++In the Parental ASM and ICRs Revised tracks, colour shows the gamete in which the methylation mark +is laid down: +
+ +| + | Oocyte germline DMR — the mark is placed in the egg, so the maternal copy is the + methylated one |
|---|---|
| + | Sperm germline DMR — the mark is placed in sperm, so the paternal copy is the + methylated one |
| + | Secondary DMR — the difference between the two copies appears after fertilisation + rather than in the gametes |
| + | Black — the gamete of origin has not been established, which is the case for every + region reported for the first time in this study |
+The Bimodal Meth track is shaded by how many cell types share a region, from light for a region +seen in a single cell type to dark for one seen in more than twenty. +
+ ++Each track can be filtered from its configuration page. The Parental ASM track filters on whether +a region is a known control region, on the gamete of origin, and on how many cell types support it. +The Bimodal Meth track filters on the individual cell types a region was called in. Clicking a +region opens a details page with the supporting SNPs, the cell types, the best adjusted p-value +and, for the parent-of-origin regions, the mean methylation of the region in published oocyte, +sperm, inner cell mass and blastocyst methylomes. The oocyte and sperm values are the direct +evidence for which parent contributes the methylated copy, and they are missing for some regions. +
+ ++Two fields record problems with the underlying data rather than biology. The Note field on the +Bimodal Meth track marks the 125 regions whose cell type list was cut off in the file the authors +published. The Lifting note field, present on all four tracks, marks regions that hg38 stretched +because sequence was inserted inside them; their boundaries no longer match the published hg19 +ones. +
+ ++Whole-genome bisulfite sequencing was done on 202 healthy samples covering around 40 primary cell +types, sorted or dissected from 135 donors, at 150 bp paired-end reads and an average of 984 +million read pairs per sample, mapped to hg19 with wgbstools. Rather than averaging methylation +over a region, each sequenced fragment covering at least three CpG sites was scored on its own and +called hyper-methylated when at least 65% of its CpGs were methylated, hypo-methylated when at most +35% were, and mixed in between. A region of at least five consecutive CpGs was called bimodal when +at least 20% of its fragments were hyper-methylated and at least 20% hypo-methylated, tested with a +log-likelihood ratio between a one-epiallele and a two-epiallele model fitted by +expectation-maximisation, with Benjamini-Hochberg correction. Bimodal regions were then intersected +with 1,360,985 gnomAD SNPs at minor allele frequency of 1% or more. In donors heterozygous at such a +SNP and with at least five fragments per allele, a Fisher exact test asked whether the genotype of +the fragment predicted its methylation state, again with FDR correction, at a threshold of 0.1. +A region where the same allele carried the methylation in every donor was taken as +sequence-dependent. A region that was bimodal regardless of genotype, and where the allele carrying +the methylation switched between unrelated donors, was taken as parent-of-origin, requiring at least +three donors with allele-specific methylation. Parent-of-origin calls were checked against 33 +mother-father-child trios by bisulfite treatment and multiplexed PCR of tongue swab DNA followed by +NextSeq sequencing, and against published gamete and early-embryo methylomes. See the reference +below for the full protocol. +
+ ++The four region sets were taken from the hg19 custom tracks the authors published, at +parental_ASM.bigbed, +ICRs-new.bigbed, +bimodal+ASM.bigbed and +bimodal.bigbed, reachable through the authors' +saved session. Those +files hold coordinates and little else, so the SNPs, cell types, p-values, gene links, control +region names and gamete methylation shown on the details pages were read out of the supplementary +data of the paper and joined onto the regions by coordinate. Region sets were not otherwise +changed. Coordinates were lifted from hg19 to hg38 with liftOver. The Parental ASM track lost 2 of +460 regions in the lift, Bimodal Meth lost 329 of 385,564, and no control region was lost; in every +case liftOver reported the region as deleted, split or only partly present in hg38. A further 33 +regions across the three tracks changed length by more than 10% because hg38 added sequence inside +them. These were kept rather than dropped, since one of them is TCEB3C, the only control region on +chr18, but each carries a note saying its boundaries are no longer reliable. One count differs from +the paper by design: the paper reports 324,759 bimodal regions while the file the authors published +for browser display holds 385,564. The build steps are in +kaplanImprint.txt and the scripts in +the imprinting script directory. +
+ ++The data can be explored interactively in table format with the +Table Browser or the +Data Integrator and exported from there to spreadsheet or +tab-sep tables. From scripts, the data can be accessed through our +API, track=kaplanParentalAsm.
+ +For automated download and analysis, the genome annotation is stored in bigBed files that can be +downloaded from our download server. The files for this track are called +kaplanParentalAsm.bb, kaplanIcr.bb and kaplanBimodal.bb. Individual regions or the whole genome annotation can be obtained using +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. The tool +can also be used to obtain features within a given range, e.g. +bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/imprinting/kaplanImprint/kaplanParentalAsm.bb +-chrom=chr21 -start=0 -end=100000000 stdout
+ +The original annotation source data can be downloaded from +the authors' server in hg19 coordinates, and the underlying sequencing data from +GEO under accession +GSE186458. The analysis code is at +github.com/yonniejon/imprint_atlas.
+ ++Thanks to Jonathan Rosenski, Tommy Kaplan and colleagues at the Hebrew University of Jerusalem for +producing this atlas and for making the region sets available as browser tracks. +
+ ++Rosenski J, Peretz A, Magenheim J, Loyfer N, Shemer R, Glaser B, Dor Y, Kaplan T. + +Atlas of imprinted and allele-specific DNA methylation in the human body. +Nat Commun. 2025 Mar 11;16(1):2141. +PMID: 40069157; PMC: PMC11897249 +
+