Extended Data Fig. 11: Relationship between mutational signatures and gene expression patterns.

a, b, Principal component analysis (PCA) of signatures across 1,159 patients (PCA on signature-specific SNVs per patient) (a) and signature–gene expression associations across 18,831 genes (PCA on adjusted P values of signature–gene expression associations) (b). The PCA on the SNVs recapitulates known interdependencies, for example, between signatures 7, whereas the PCA on the signature–gene association studies also emphasizes functional relatedness, for example, between signatures 2 and 13. c, Hierarchical clustering of signatures. The numbers at the nodes indicate the number of genes commonly associated with two to four respective signatures. The dendrogram shows genes that are associated with more than one signature mostly owing to similar SNV patterns of these signatures across patients. d, Frequency of number of significantly associated genes per signature (FDR ≤ 10%). Although many signatures are significantly associated with a few genes, 18 signatures are associated with more than 20 genes. Signature 9 is associated with more than 350 genes. Vice versa, 1,009 genes are associated with only one signature, 129 with two, 32 with three, 5 with four and 1 with five signatures. e, f, Mutational signature–gene associations, depicting positive associations between the expression of the canonical APOBEC pathway genes APOBEC3B (e) and APOBEC3A (f) and signature 2. The associations within the three cancer type with the strongest correlation between signature and gene expression (hepatocellular carcinoma (Liver–HCC), bone leiomyosarcoma (Bone–Leiomyo) and prostate adenocarcinoma (Prost–AdenoCA)) are shown.