Two characteristic CNVs on chromosome 8 and their corresponding paired-end sequencing signatures. Gray reads give rise to read depth measurements, represented as black circles. Blue reads correspond to discordant read pairs and contribute to read pair measurements denoted as blue squares. Split reads and their corresponding counts are represented in green. Hybrid green/blue reads provide evidence of split reads combined with abnormal read pair distance. (a) Read depth signature for well described homozygous deletion on chromosome 8. Reads are absent inside the deleted region. (b) Read pair signature for the same deletion as (a). The distance of the pairs spanning the deletion is significantly increased compared to the expected insert size. (c) Combination of read depth, read pair and split read signatures. Two split reads that span the breakpoints of the deletion were identified. The joint analysis of all the sources improves the breakpoint detection. (d) Read depth signature for multi-copy tandem duplication on chromosome 8. Significantly more reads are present inside the duplicated region. (e) Read pair signature for the same duplication as (d). The read pair distance appears significantly decreased compared to the expected insert size. (f) Combination of read depth and read pair signatures provides improved breakpoints. The split reads detected in the region are used to rescue their orphaned pair and are thus incorporated into the read pair signature.
Bellos et al. Genome Biology 2012 13:R120 doi:10.1186/gb-2012-13-12-r120