Fig. 2. Our model for the effects of copy number alterations on mutated-read fractions in DNA profiles.

a For each mutation in each biopsy s, the mutated-read fraction is a function of the true proportion of profiled cells with the mutation (mutation frequency) φ_s, the copy number of the reference allele in cells without the mutation δ_s, and the copy numbers of the reference and the mutated allele in tumor cells with the mutation, ${\delta }_{\mathrm{s}}^0$ and ${\delta }_{\mathrm{s}}^{\mathrm{a}}$, respectively. The frequency of tumor and WT cells without the mutation is (1 − φ_s) and the two reference alleles can be assumed to have a combined copy number of 2δ_s. c–e To compare inference methods we synthetically generated profiling data based on parametrized simulated copy number distributions. b Shown are representative phylogenies and c a representative cellular composition matrix, as well as d density plots of average copy numbers across profiles of TCGA-profiled hepatocellular (HCC) and breast (BRCA) carcinomas. These include the distribution of copy numbers in two individual HCCs (HCC1 and HCC2) and across all HCCs (black) and all BRCAs (blue); copy numbers ranged from 0 to >260×. e Simulated copy numbers, including simulations of more-stable and less-stable cancers, ranged from 0× to 15× copies.