Extended Data Fig. 2: Detection of somatic mutations in small clones of skin cells with high specificity and sensitivity.

a, Allelic dropout declines rapidly as a function of clone size. Each data point represents the percent of germline SNP alleles that could not be detected for a given clone as a function of the number of cells within the clone. b, Establishing a VAF cutoff to infer somatic mutations within a clone. The left panel depicts the VAFs for known somatic mutations and known amplification artefacts from a single clone. The right panel depicts a ROC curve, showing the VAF at which sensitivity and specificity of somatic mutation calls would be maximized when inferring the mutational status of variants based on VAF alone. Variants that fell within expressed or phase-able portions of the genome were classified as mutations or artefacts as described (Fig. 1c, d). The remaining variants were inferred based on the VAF cutoff, which maximized sensitivity and specificity of somatic mutation calls. c, d, The specificity (c), and sensitivity (d), of inferred somatic mutations as a function of clone size. The mean specificity and sensitivity of inferred somatic mutations was respectively 98.83% and 98.60% for all clones of at least 5 cells. All trendlines correspond to a moving average.