Extended Data Fig. 1: Exemplar tumour genome demonstrating mutation asymmetry from lesion segregation.
a, Mutational summary of one DEN induced tumour; the tumour genome represented by the shared x-axis and chromosome boundaries marked with dashed vertical lines. Mutations are called relative to the forward strand of the reference genome and shown as coloured points stratified type (C → N, T → N, A → N, G → N). Y-axis positions show the genomic distance to the next mutation of the same type and plotted on a log10 scale. Mutations of type T → N and A → N are complements of each other and plotted on opposite sides of the asymmetry segmentation track with inverted y-axis orientations (y-axis arrows). The same for C → N versus G → N mutations. Genomic segmentation by T → N/A → N mutation asymmetry is plotted showing genomic segments where mutations have arisen from forward strand lesions (blue), reverse strand lesions (gold), or where one chromosome has forward and the other reverse strand lesions meaning that they cancel each other out (grey). Hemizygous X chromosomes are always mutationally asymmetric. The asymmetry score is calculated as S = (forward-reverse)/(forward+reverse) where forward and reverse are the sequence composition adjusted rates of T → N and A → N mutations. Both average total mutation rate and read coverage are typically uniform across the autosomal portion of the tumour genomes. b, The mutational asymmetry calculated from T → N/A → N mutations (x-axis) and C → N/G → N mutations (y-axis) in 5 Mb windows over the genome is closely correlated, consistent with the interpretation that most mutagenic adducts in these tumours are on T and C nucleotides2 and supported by reduced mutation rates when T and C are on the transcriptional template strand (Extended Data Fig. 7).
