Both tumor purity and ploidy will affect the local depth of sequencing necessary to detect point mutations. For example, suppose that a region is present at 6 copies with only 1 copy carrying a mutation, in a sample that has 50% contamination with normal cells. In this case, only 1 of 8 alleles at this locus (6 from the cancer cells and 2 from the normal cells) carry the mutation (Supplementary Fig. 7a). We therefore expect that the mutation will be observed in only 12.5% of reads. Given this allelic fraction, local sequence coverage of 33-fold is required to detect the mutation with 80% sensitivity, assuming a sequencing error rate of 10-3 per base and a false positive rate controlled at <5×10-7, (Online Methods, Eq. 9, Supplementary Fig. 7b).
