Features of grade-CpGs. A, Supervised clustering analysis of the 1,985 grade-CpGs. Donor’s number and corresponding lesion grade are shown for each sample. Note the tendency for hypermethylation in the advanced lesion group. Heatmap color and contrast were enhanced to improve readability, as changes in DNA methylation were overall weak (see intensity distribution above upper right corner of heatmap). B, Proportion of grade-CpGs with positive (i.e. hypermethylation with lesion grade) and negative correlation between lesion grade and intra-pair Delta-Beta. C, Intra-pair Delta-Beta and position of grade-CpGs (black diamonds) and the previously described dm-CpGs (open circles) in the PDGFA and PRDM16 gene-body. Notice that grade-CpGs reinforce the dm-CpG profiles. D, Grade-CpG mapping relative to gene compartments. Solid bars, observed distribution; open bars, distribution of 450 k array probes.