Density of all genomic 11-mers (blue-scale) according to their genomic spans (x-axis) and mutation rates (y-axis). The mean mutation rate of the dataset (5.96 SNV/Mb/patient) is indicated by a solid line (baseline). Dashed lines indicate a 2- and 5-factor mutation rate increase. Colored curves (shades of red) represent the nominal p -value thresholds for a given 11-mer mutating at a significantly elevated rate compared to the baseline, with 11-mers above and to the right considered significant at the given level. If all 2,097,090 11-mer mutation rates were tested separately, the nominal p -value threshold of 10 –9 (red) would provide a conservative bound for significance after (Bonferroni) multiple testing correction. In the downstream analysis of this study, we focus on a total of 817 combined sets of 11-mers, with extended spans compared to individual 11-mers. The nominal p -value threshold of 10 –5 (organge) conservatively defines the region of mutation rates and spans where they would be significant after multiple testing correction.
