Spectrum of base substitutions by mutation and polymorphism. (A) Observed-to-expected ratios were defined as the ratio of the base change frequency of mutation (red) and polymorphism (blue) in TFBSs to the overall base change frequency in open chromatin. Only changes from the reference homozygote were considered. (B) Observed-to-expected ratios were defined as the ratio of the relative enrichment of substituted dinucleotides in TFBSs to the relative enrichment of all dinucleotides in TFBSs. (C) For each TFBS CpG, differential methylation levels between lymphocytes and other cell types (embryonic stem cells (ESC), hematopoietic progenitor cells (HPC), and neutrophils) were calculated. (D) Observed-to-expected ratios of base changes at TFBS CpGs were calculated as the ratio of the substitution frequency of mutation and polymorphism in TFBSs to the overall substitution frequency in open chromatin.