Extended Data Fig. 3: Topographical characteristics of 56 LCINS and 68 lung cancers from smokers exhibiting SBS4 activity.
From: The mutagenic forces shaping the genomes of lung cancer in never smokers
a,b, Distribution of SBS4 mutations with replication timing in our cohort of never-smokers (a) and in the smokers from the PCAWG cohort (b). Data are separated into deciles, with each segment harbouring 10% of the observed replication time signal in the x-axis, and the normalized mutational density displayed in the y-axis. Black dashed lines represent the behaviour of simulated mutations. c,d, Association of SBS4 mutations with nucleosome occupancy in never-smokers (c) and smokers (d). The solid blue line represents real somatic mutations, whereas the dashed grey line indicates the distribution of simulated mutations. Both lines show the average nucleosome signal in the y-axis, using a genomic window of 2 kilobases centred around the SBS4-associated mutations in the x-axis. e,f, Strand asymmetry of SBS4-associated mutations in comparison to simulations and considering lagging and leading DNA strands, transcribed and untranscribed DNA regions and genic and intergenic genomic locations in never-smokers (e) and smokers (f). The number of circles represents the odds ratio and the colour the corresponding strand/region of statistically significant asymmetries.
