Fig. 3

Mutation signature analysis of five hepatocellular carcinoma samples in different chromatin states or with different methylation levels. a Frequencies of the 96 substitution patterns of three extracted mutational signatures. The stability of the signature and the most similar COSMIC signature are shown in Supplementary Table 4. b Contribution of the three mutational signatures to each tumor sample according to the chromatin state. The y-axis indicates the number or contributions of each signature in the mutations. In each sample, significant differences were observed between active and inactive chromatin states (P < 2.2e–16, Pearson’s Χ²-test). The contribution of Signature B (which corresponds to COSMIC Signature 16) in active state was significantly higher than that in the inactive state (P < 2.2e–16, Pearson’s Χ²-test). c The contribution of three mutational signatures in genomic regions of different methylation levels. In each sample, the contribution was significantly different between high and low methylation levels (P < 2.2e–16, Pearson’s Χ²-test). The proportions of Signature A (which corresponds to COSMIC Signature 1) and B in highly methylated regions was significantly higher than the proportions in low methylated regions (P < 2.2e–16 in Sig. A, P < 2.8e–05 in Sig. B, Pearson’s Χ²-test). d The contributions of three signatures in 15 epigenomic segments. e Odds ratio of Signature B in a particular segment compared with the other segments. *P < 0.05, **P < 0.005, ***P < 0.0005 tested with Fisher’s t-test