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Chunk #86 — Online Methods — 6. Differentially Methylated Regions (DMRs) and DNA methylation variation — 6.4 DNA methylation variation

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Integrative analysis of 111 reference human epigenomes.
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For variation in methylation of each chromatin state across epigenomes (Fig. 4g, Extended Data 4f), we first excluded any contiguous chromatin state region containing less than 3 CpG sites. Then, the mean of the methylation level for all contained CpG sites was calculated for each region, and for each epigenome, density values were calculated for these mean methylation values between 0% and 100%, with density values estimated over n=1000 points with a gaussian kernel, with a default bandwidth of ‘nrd0’. Finally, for each chromatin state, we plotted the ln(density+1) for each epigenome as rows, with the color scale set with white as the minimum ln(density+1) value and red, green, or blue, for WGBS, mCRF, and RRBS, respectively, set as the maximum ln(density+1) value in the matrix. Rows were ordered by the epigenomic lineage and grouping ordering shown in Fig. 2a; In Extended Data 4f, epigenomes were first grouped by methylation platform, and then ordered by Fig. 2a within each platform. The chromatin state methylation profiles in the cell lines vs primary cells/tissue cells were analyzed using a mixed model with