Fig. 2: In silico mixing strategy and optimal CCF calculation metrics.

a A schematic illustrating the subsampling and merging process used to create in silico mixtures of real tumour samples. The top diagram shows the three-cluster in silico mixtures, created by mixing the two metastasis samples in different proportions. The bottom diagram shows the methodology for creating the four- and five-cluster mixtures, which separates each mixture sample into even and odd chromosomes, then subsamples these samples to create additional clusters. The resultant CCFs are based on the subsampling percentage of each odd or even chromosome sample, rather than the sample proportion (as in the three-cluster mixtures). b The CCF ground truth (based on sample membership) versus optimal SV and SNV results (based on transformed variant allele frequencies from the true cluster mean) for a representative three-cluster mixture and the four- and five-cluster mixtures. c Mean per-variant CCF error of optimal SNV and SV CCFs compared with the expected, ground truth CCF. d ROC curves for classifying variants as clonal or subclonal based on optimal variant CCFs.