We analyzed the distribution of purity and ploidy values in cancer samples analyzed for allelic copy number 35, 21, 33 to determine an appropriate depth of sequencing coverage needed to detect clonal mutations with power 0.8 in each sample. For this purpose, we calculated the number of reads needed to detect a mutation present in one copy at a locus present at the average copy number, given the sample's purity. (One could alternatively choose a particular percentile on the copy-number distribution.) For such a locus, we found that 30× local coverage would suffice for most samples (Supplementary Fig. 7d). By contrast, a locus of average copy number with a mutation carried in a subclone at 20% frequency would require coverage of ∼ 100-fold to allow detection in about half of the samples (Supplementary Fig. 7e). Using these calculations and the distribution of local coverage along the genome (which depends on the specific sequencing technology), one can determine the average coverage necessary to obtain sufficient power in a predefined fraction of the genome (e.g. >80% power in >80% of the genome).
