Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity (Cell Reports)

Shi et al. report that standard coverage whole-exome sequencing and bioinformatics pipelines cannot discriminate between genuine intratumor genetic heterogeneity and sequencing artifacts. Although aggressive minimum depth filtering would not improve the false detection rate of subclonal mutations, excluding mutations in low-mappability regions or in certain mutational contexts could help.