Fig. 4: Functional and regulatory role of DMRs.

a Density plot of hyper (red), hypo (blue), and hypo-blocks (green) Differentially Methylated Regions (DMRs) around ±10 Kbp of TSS. b Box plot showing the distribution of the fraction of DMRs across the distinct tumor types annotated to the different genic features for hyper-DMRs, hypo-DMRs, and hypo-blocks. c Box plot of ChromHMM states from matched normal tissues. Each dot represents a tumor type, and the fraction of segments within each class of DMRs is reported. Neutral refers to the not-differentially methylated genome obtained from the Rocker-meth segmentation. Statistical significance is estimated using pairwise Wilcoxon test. d Dot plot showing the Odds-ratio of the pan-cancer enrichment of hyper (red) and hypo (blue) Differentially Methylated Regions (DMRs) in under-expressed (left) and over-expressed (right) genes estimated by Fisher Exact Test (FET) for different genic annotations. Error bars show the 95% confidence interval. e Lollipop plot reporting the Odds-ratio (OR) of the enrichment (by proportion test) of Transcription Factors in the set of differentially expressed genes deregulated by hyper-DMRs (red) and hypo-DMRs (blue) in their regulatory regions. The size of the dots associates (inversely) with p-values. f Fraction of matched ChromHMM states in DMRs associated with transcription factors, grouped by deregulation. -1: TF is downregulated, 0: TF is not deregulated. 1 TF is upregulated (FDR <0.05 is used to call differential expression). g Bar plots showing the distribution of TF families for the TFs affected by DMRs.