Figure 4.

Validation of iiDMRs in an independent cohort. (A) For this analysis we used 30 MZ twin pairs from [20] whose whole blood DNA methylation profiles were generated by Illumina 27K arrays. We defined low and high expression based on the RNA-seq data we generated in this study from CD14+ cells. High expression: >1 FPKM, Low expression: <1 FPKM. (B) Promoter iiDMRs in the test set are preferentially enriched at regions low in H3K4me3 and high in H3K27me3, and in regions that lack both of these marks in hES cells. The analysis was performed essentially as described in the legend for Figure 3D. (C) Intra- and inter-MZ pair iiDMRs are correlated in the discovery and validation cohorts. For the 30 MZ pairs from [20], we measured intra-pair methylation variability by taking the RMS (root-mean-square) methylation differences for each probe. We also calculated a similar inter-pair variability measure by permuting the pairs. For each of the five possible pairs in the current study, we bin probes by methylation difference, and plot the mean inter- and intra-pair validation methylation variabilities. (D) For the 30 MZ pairs from [20], we calculated intra-pair and inter-pair RMS methylation variability as above and show a scatter plot for all probes on the Illumina27K array (with exclusions as described in the Methods for the Illumina450K data).