Figure 1.

A gold standard of the cell-to-cell heterogeneity in DNA methylation

A. Representative scBS-seq reads from cell 1 that were mapped to the mouse genome (Chr 9: 35,113,079–35,113,167) are shaded. Cytosine in a BS-seq read represents a methylated CpG site, whereas thymine represents an unmethylated CpG site. Examples of heterozygous (A₁/A₂, Chr 9: 35,113,079–35,113,167 in cell 1) and homozygous (A₁/A₁, Chr 17: 39,981,368–39,981,383 in cell 14) epigenetic status are shown, respectively. The identity and number of all the methylation patterns in a cell are shown. Circles represent 4 consecutive CpG sites in a DNA segment, among which closed ones represent methylated sites and open ones represent unmethylated sites. Methylation patterns are ranked by their frequencies and A_i represents the ith methylation pattern. B. The distribution of the log₂-transformed frequency ratio between the top 2 methylation patterns. The dashed line indicates the cutoff of the frequency ratio. If there is only one methylation pattern present in a DNA segment, a “pseudo” methylation pattern was added with a read count equal to 1.