The sensitivity and specificity of any somatic-mutation calling method varies along the genome. They depend on several factors, including the following: depth of sequence coverage in the tumor and a patient-matched normal sample; the local sequencing error rate; the allelic fraction of the mutation; and the evidence thresholds used to declare a mutation. Understanding how sensitivity and specificity depend on these factors is necessary for designing experiments with adequate power to detect mutations at a given allelic fraction, as well as for inferring the mutation frequency along the genome, which is a key parameter for understanding mutational processes and significance analysis19,20.
