Somatic CNVs can be detected by identifying deviations either from the expected depth of sequence or in the expected distances between paired-end sequencing reads. Similarly, inversions can be identified through differences in the orientations of paired-end sequencing reads. Numerous approaches have been developed to identify CNVs from WGS (7, 87–89), and most can be applied directly to identify somatic mutations. For example, recent studies using WGA in conjunction with WGS have identified megabase-scale de novo CNVs in human and mouse neurons based on differences in read-depth across genomic bins (6–9). CNVs are more difficult to identify using WES due to the biases encountered during the capture of target exons (90).
