Extended Data Fig. 1: Modeling of mutation probabilities based on extended nucleotide contexts.

a, We applied the composite likelihood model to COSMIC mutation signatures. For each trinucleotide context, we compared the original mutation frequency against the mutation frequency returned by the composite likelihood model based on Pearson correlation. Dot colors reflect base substitution types. b, For six base substitution types, we plotted the original mutation probability (based on 11873 samples) against the prediction of the composite likelihood model, which we derived as the product of the mutational likelihood of its reference nucleotide and its substitution type. Each dot represents a cancer type. Pearson correlations are annotated at the bottom right. The number of samples per cancer type can be found in Extended Data Fig. 5. c, For three cancer types (bladder, n = 317 samples; endometrium, n = 327; skin, n = 582) we examined whether nucleotides outside the trinucleotide context affected mutation probabilities. For this purpose, we compared mutation probabilities, modeled based on tri- (blue) and 7-nucleotide contexts (yellow), with original mutation probabilities based on context-specific mutation counts. Data points are sorted according to the modeled mutation rates, derived from the 7-nucleotide context (x-axis). Black circles indicate ratios between the observed probabilities and the corresponding trinucleotide-specific likelihoods (y-axis). Similarly, the orange line displays the ratio between the likelihoods, derived from the 7-nucleotide and trinucleotide contexts, respectively (y-axis). Local mutation probabilities vary across positions surrounded the same trinucleotide context. Accounting for extended nucleotide contexts reduces this heterogeneity.