+Most genes are expressed from both the maternal and the paternal copy of a +chromosome. A small number of genes break this rule: they are +imprinted, meaning that only the copy inherited from one parent is +active while the other copy is silenced. The mark that keeps the two copies +apart is DNA methylation. At an imprinted locus, one allele carries methylated +CpG sites and the other does not, a pattern called allele-specific methylation +(ASM). Regions with this pattern are candidates for imprinting control regions, +the switches that set the expression of whole gene clusters. +
+ ++Whole-genome bisulfite sequencing reads are long enough to cover several CpG +sites at once, so the methylation states of neighboring sites on the same DNA +molecule can be read together. When the reads at a locus fall into two clearly +separated groups, one mostly methylated and one mostly unmethylated, that locus +shows allele-specific methylation. This track shows, for every CpG site in the +genome, the fraction of MethBase2 human methylomes in which the site was called +part of an allelically methylated region (AMR). Values range from 0 to 1. High +values mean that many independent samples show two differently methylated +alleles at that site, which is the expected signature of a constitutive +imprinted region. Lower but non-zero values point at loci where allele-specific +methylation is restricted to certain tissues or is driven by sequence variation +rather than by imprinting. +
+ ++The score is a summary across samples, not a measurement in any single sample. +A value of 0.5 does not mean that half of the DNA molecules are methylated; it +means that about half of the surveyed methylomes had an AMR call covering that +CpG. +
+ ++The track is a signal graph with one value per CpG site. The default vertical +range is 0 to 0.5, since even the strongest known imprinted regions rarely +exceed that fraction across a set of samples this diverse. The range, the +graph height, the smoothing window and the aggregation function can all be +changed on the track configuration page. Positions between CpG sites carry no +data and are drawn as gaps. +
+ ++The per-sample methylation levels, hypomethylated regions and read coverage +that this summary is derived from are published by the Smith lab as a track +hub, which can be loaded from +http://smithlab.usc.edu/trackdata/methylation/hub.txt +or found in the list of public hubs. +
+ ++MethBase2 collects publicly available whole-genome bisulfite sequencing runs +from the NCBI Sequence +Read Archive and reprocesses all of them through one uniform pipeline built +on DNMTools. +Reads are mapped with abismal, duplicates are removed, the bisulfite conversion +rate is estimated, and per-site methylation levels are computed and symmetrized +across the two strands of each CpG. A methylome enters the browsable collection +only if its bisulfite conversion rate is at least 0.9 and at least 70% of CpG +sites are covered, which in practice implies well above 1x average coverage. +Allelically methylated regions are then called per methylome with the +amrfinder +command. It slides a window of 10 CpG sites along the genome and fits two +models to the reads in each window, one in which both alleles share a single +methylation state and one in which the two alleles have separate states. The +window is called an AMR when the two-allele model fits significantly better, +using a likelihood ratio test with a false discovery rate correction; windows +need at least 4x mean coverage per CpG to be tested, and neighboring AMRs closer +than 1 kb are merged. The statistical model is described in Fang et al. (2012). +The score shown here is the number of methylomes whose AMR set covers a given +CpG, divided by the number of methylomes tested. +
+ ++The data file was downloaded from +http://smithlab.usc.edu/methbase/data/common/hg38/hg38.asm.bw, +the "common" section of the MethBase2 track hub at +http://smithlab.usc.edu/trackdata/methylation/hub.txt. +The file is a bigWig and was used as it is, without reformatting or +recalculation; it covers 29,401,795 CpG positions on the 25 main chromosomes +(chr1 to chr22, chrX, chrY, chrM) and no positions were dropped. The steps we +ran are documented in the +imprinting makeDoc. +
+ ++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=methBaseAsm. +
+ ++For automated download and analysis, the annotation is stored in a bigWig file +that can be downloaded from +our download server. +The file for this track is called hg38.asm.bw. Individual regions or the +whole annotation can be obtained using our tools bigWigToBedGraph or +bigWigSummary, which can be compiled from the source code or downloaded +as precompiled binaries for your system. Instructions for downloading source +code and binaries can be found +here. +The tools can also be used to obtain values within a given range, e.g. +bigWigToBedGraph http://hgdownload.soe.ucsc.edu/gbdb/hg38/imprinting/methBaseAsm/hg38.asm.bw -chrom=chr15 -start=24950000 -end=25200000 stdout +
+ ++The original data can be downloaded from the MethBase2 track hub at +http://smithlab.usc.edu/trackdata/methylation/hub.txt. +
+ ++Thanks to Andrew D. Smith and the Smith lab at the University of Southern +California for building MethBase2 and for making the allele-specific +methylation summary available. The collection is maintained at +https://github.com/smithlabcode/methbase. +
+ ++Fang F, Hodges E, Molaro A, Dean M, Hannon GJ, Smith AD. + +Genomic landscape of human allele-specific DNA methylation. +Proc Natl Acad Sci U S A. 2012 May 8;109(19):7332-7. +PMID: 22523239; PMC: PMC3358917 +
+ ++Song Q, Decato B, Hong EE, Zhou M, Fang F, Qu J, Garvin T, Kessler M, Zhou J, Smith AD. + +A reference methylome database and analysis pipeline to facilitate integrative and comparative +epigenomics. +PLoS One. 2013;8(12):e81148. +PMID: 24324667; PMC: PMC3855694 +
+