Extended Data Fig. 5: Mutation signatures of the Pole mutant cell lines.

a, Schematic explanation of the baseline and de novo SNVs in parental and mutant cell lines. b, Transcriptional strand bias (TSB) of the six base substitution categories of the baseline and de novo mutations from the B16F10 parental and Pole^P286R mutant cell lines. De novo mutations in the parental and the Pole^P286R mutation cell lines showed distinct transcriptional strand bias, indicating that these mutations are generated by different biological processes. c, The 192 TSB base substitutions in tri-nucleotide sequence contexts of the three NMF extracted de novo TSB mutational signatures from the baseline and de novo SNVs of the B16F10 parental and Pole^P286R mutant cell lines. d, Contribution of the three NMF extracted de novo TSB mutation signatures to the baseline and de novo mutations in the B16F10 parental and Pole^P286R mutant cell lines showed that the TSB-Sig.B is exclusively contributed to the de novo mutations discovered in the B16F10 Pole^P286R mutant cell lines. e, Cosine similarity of the de novo mutational TSB signatures with COSMIC TSB-SBS signatures v3. The TSB-Sig.B is highly similar to the POLE/D1 function-assocaited signature TSB-SBS10b (cosine similarity of 0.84). f, COSMIC SBS signatures extracted from B16F10 parental and Pole^P286R mutant cell lines by NNLS method. The POLE/D1 function-associated signature SBS10b can only be extracted from the de novo SNVs of the Pole^P286R mutant samples.