Discordant paired-end and split-read methods will generally not perform well for CNV detection from exome or targeted-capture sequence data, as they require the capture of at least one of the breakpoints. In this case, algorithms that examine the sequence depth of coverage are the primary means for detecting CNV. Read depth methods for CNV can be applied to both whole genome and targeted-capture data but require different considerations (Figure 2). In the case of whole genome sequence data, the pattern of deletions and duplications is readily apparent from the sample's coverage profile, albeit at low resolution. The computational problems here are to accurately localize the breakpoints and to determine the number of copies present in each segment. Several software packages have been developed to address these issues; some of the existing algorithms are intended to detect CNV based on the read epth profile of a single sample, whereas others require a control sequence for comparison.
