This detailed understanding of the factors determining sensitivity is critical for targeting the appropriate depth of sequencing. Because the allelic fraction of a mutation depends on the tumor purity, local copy-number and clonality8, one can calculate the sequencing depth required for a desired sensitivity on a tumor-specific basis. Also, given a sequencing data set we can calculate the sensitivity to have detected a mutation with a particular allelic fraction for each base along the genome. This allows us to assert the absence of a mutation (with a specified allele fraction), which is particularly important in a clinical setting.
