Extended Data Fig. 6. Benchmarking of ParallelGDDetect for detection of parallel subclonal whole genome doubling (WGD).

a. A scatter diagram displaying for each tumour region between the fraction of the genome with major copy number of at least 2; the mean allelic difference; the ploidy; purity; and subclonal WGD status (determined using heterogeneity of ploidies). b. An identical scatter diagram depicting the fraction of the genome with at least a major copy number of 3. c. An example of a subclonal mutation cluster present in two whole genome doubled regions which contains mutations at copy number ~2 in areas of the genome without gains, indicating that these mutations occurred before the whole genome doubling event (pre-WGD) in these regions, but is absent in other whole genome doubled regions. d. A stacked histogram indicating the number of regions with truncal clusters harbouring different fractions of mutations with estimated mutation copy number >1.5, split by regions estimated to harbour 0, 1 or 2 WGD events. e. A stacked histogram indicating the number of regions with truncal clusters harbouring different fractions of mutations with estimated mutation copy number >1.5, restricting to genomic regions where the major copy number was equal to 2^(number of WGD events in that region), split by regions estimated to harbour 0, 1 or 2 WGD events. f. Benchmarking of ParallelGDDetect in 500 simulated tumours where 460/460 tumours lacking multiple subclonal WGDs were correctly classified (100% specificity & sensitivity) and 27/40 tumours which harboured multiple subclonal WGDs were correctly classified (68% specificity). g. An association between SCNA ITH and the number of subclonal WGD events. h. An association between mutational ITH and the number of subclonal WGD events. i. An association between the fraction of subclonal mutations attributable to APOBEC mutagenesis (SBS2/SBS13) and the number of subclonal WGD events.