Finally, we have also compared the sensitivity of the methods using previously reported sequencing data and validated mutations in the COLO-829 melanoma cell line37 (Supplementary Table 2). Although MuTect is slightly more sensitive than the other methods, this dataset represents a pure cell line with easily detectable high allelic fractions events (median=0.55) and thus does not expose differences between methods. By running MuTect and the other mutation callers we were able to find additional mutations not originally reported (Supplementary Tables 3,4), underscoring that comparisons to mutations reported in the literature typically underestimate the sensitivity as the complete ground truth set of somatic mutations is often unknown.