Mutation drives evolution and underlies many diseases, most prominently cancer . Of the newly developed genomic technologies, next-generation DNA sequencing (NGS), in particular, has revolutionized the scale of study of biological systems and has already started to enter the clinic where it is expected to enable a more personalized approach to patient care . Unlike conventional sequencing techniques, which simply report the average genotype of an aggregate of molecules, NGS digitally tabulates the sequence of individual DNA fragments, thereby offering the unique ability to detect minor variants within heterogeneous mixtures . Already, NGS has been used to characterize exceptional diversity within microbial viral and tumor cell populations, and many low frequency, drug-resistant variants of therapeutic importance have been identified . NGS has also revealed previously underappreciated intra-organismal mosaicism in both the nuclear and mitochondrial genomes . This somatic heterogeneity, along with that underlying adaptive immunity], is an important factor in determining the phenotypic variability of disease.