Fig 6. Enrichment of TFBSs among age-DMRs.

A) Left top panel depicts the age of the individuals from which the blood samples were taken, sorted by increasing age. Heatmap depicts relative DNA methylation levels for the top 500 age-hypomethylated and top 500 age-hypermethylated DMRs (blue = relative high DNA methylation, yellow = relative low DNA methylation), with samples sorted by increasing age. Right panel depicts (with black lines) which DMRs overlap with transcription factor binding sites (TFBS) for a number of TFs which exhibited highly significant enrichment either for age-hypermethylated or age-hypomethylated DMRs (or both). Below the panels we give the odds ratios (OR) and Fisher-test P-values (P) of enrichment of the corresponding TFBSs among age-hypermethylated and age-hypomethylated regions of the top 5% of age-DMRs. B) Combinatorial enrichment analysis of TFBSs. TFs have been sorted according to the strength of association (P-value) of their binding profile with the association of a region’s DNA methylation with age, as assessed from a multivariate linear regression model. Color code for P-values: white (P > 0.01), pink (P < 0.01), red (P < 1e − 5), brown (P < 1e − 10). Below P-value bar we show the corresponding estimated t-statistic in the multivariate analysis (magenta = strongly significant (P < 0.001) positive values, cyan = strongly significant (P < 0.001) negative values).