Fig. 2.

Synonymous rates are lower at exon flanks compared with cores when controlling for multiple variables. a, b Comparison of SSM mutational load between exon flanks and cores in which CpG sites were masked out. c, d SSM from TCGA exomes (c) and ICGC WGS (d) were segregated into six equivalent classes of substitutions and normalized by the number of reference nucleotides. e SSM relative to nucleosome occupancy. Top 25% (bottom 25%) of the nucleosome occupied regions are designated as high (low). f SSM relative to DNA replication timing. g SSM relative to mismatch repair status in TCGA STAD. h SSM comparison in alternative vs constitutive exons. Statistical significance was computed using Wilcoxon signed rank test. The y-axis unit is SSM rate per bp per tumour. Error bars, 95% CI computed by bootstrapping