Fig. 2: Signature analysis uncovers distinct mutagenic processes focused at constitutive origins.

a Cancer sample clustering based on the cosine similarity of their origin trinucleotide mutational signature. Each signature at origin domains was corrected to adjust for local trinucleotide composition and background values from neighbouring origin flanking domains. Only whole-genome-sequenced cancer samples with at least 50 mutations at origins were considered. b Distribution of cancer types and primary sites within the five identified clusters of tumours. c Origin-associated mutational signatures for tumour clusters. Signatures were computed from aggregated mutation calls at origin domains for clustered cancer samples and corrected as previously. d Local exposure to mutational signatures associated with clustered tumours. Signature contributions are corrected for background origin flank values. e Total mutation count at origins and (f) origin/origin flanks mutation density ratios for individual cancer samples grouped by clusters. Box plot show medians and interquartile ranges. Individual cancer samples are represented as grey dots.