Fig. 3
From: Sequence dependencies and mutation rates of localized mutational processes in cancer
Assignment of cohorts and 11-mers to mutational signatures. a Stratification of genomes based on mutational signature load into 60 so-called activity cohorts. Each activity cohort comprises a number from 0 to 2049 genomes (median 48). The cohort with active signature 17b has 240 patients. b Fraction of cancer types in each activity cohort. Cancer type color legend can be found in Fig. 1a. c Each mutation has a posterior probability distribution of possible explanatory signatures (piechart). The average posterior probability distribution for an 11-mer is used to evaluate its most likely explanatory signature. On average, the mutations in 11-mers AGAACTTCGAG and AAAACTTATGC are most like explained by signature 17b, while mutations in CCCAGCACTTT are most likely explained by signature 18. All mutated 11-mers in the cohort are used as a background (red column). All 11-mers with signature 17b as the most likely signature make up a set of signature 17b-assigned 11-mers used for further analyses (blue column). The color legend for the piecharts can be found in panel d. d Color legend for signature association (top). Mutation rate of mutated 11-mers within each activity cohort (bottom). The mutation rates (left y-axis) are compared to the pan-cancer mutation rate (5.96 SNV/Mb/patient; grey dashed line) and differences are represented as a fold-change (right y-axis). e Mean mutation rate of each signature-assigned 11-mer set (blue). The mutation rates (left y-axis) are compared to the global mutation rate (5.96 SNV/Mb/patient; grey dashed line) and represented as a fold-change (right y-axis). f Fold-change from activity cohort mutation rate to signature-assigned 11-mer sets mutation rate. g Fraction of the genome spanned by 11-mers selected in each analysis step. h Sequence information content visualized by bit logo plots. The surprise (information) of observing a nucleotide is measured in bits derived from the Kullback–Leibler divergence with the reference genome as a background (A = 29.5%; C = 20.5%; G = 20.5%, T = 29.5%; “Methods”)