Extended Data Figure 7. Non-random distribution of mutational signatures throughout the genome.

a, Context- and replication-timing-dependent mutation spectrum of the three mutational signatures depicted in Fig. 2a. Indicated is the contribution of each trinucleotide to the signatures (order is similar as in ref. 11), subdivided into the fraction of the trinucleotide-change present in early, intermediate or late replicating genomic regions. b, log₂ ratio of the observed and expected number of mutations per indicated base substitution (summed over all trinucleotides) in early-, intermediate- and late-replicating genomic regions for each of the signatures depicted in a. log₂ ratio indicates the effect size of the bias and asterisks indicate significant DNA-replication-timing bias (P < 0.05, binomial test). c, log₂ ratio of the total number of observed and expected mutations in early-, intermediate- and late-replicating genomic regions for each signature depicted in a. log₂ ratio indicates the effect-size of the bias and asterisks indicate significant DNA replication timing bias (P < 0.05, binomial test). d, Context- and transcriptional-strand-dependent mutation spectrum of the three mutational signatures depicted in Fig. 2a. Indicated is the contribution of each trinucleotide to the signatures (order is similar to that in ref. 11), subdivided into the fraction of the trinucleotide-change present on the transcribed and untranscribed strand. e, log₂ ratio of the number of mutations on the transcribed and untranscribed strand per indicated base substitution for each signature depicted in d. log₂ ratio indicates the effect size of the bias and asterisks indicate significant transcriptional strand bias (P < 0.05, binomial test). f, The dN/dS ratio for all protein-coding somatic point mutations observed in all ASCs per tissue type. Error bars indicate 95% confidence intervals (likelihood ratio test).