Somatic CNV Smoothing

The segmentation stage might produce adjacent or nearby segments that are assigned the same copy number and have similar depth and BAF data. This can result in fragmentation of a region with consistent true copy number into several pieces, which may be undesirable for downstream use of copy number estimates. Additionally, for some uses, it may be preferable to smooth short segments that would be assigned different copy number whether due to a true copy number change or an artifact. To reduce undesirable fragmentation, initial segments may be merged during a post-calling segment smoothing step.

After initial calling, segments shorter than the specified value of --cnv-filter-length are deemed negligible. Among the remaining non-negligible segments, successive pairs are evaluated for merging. Two successive segments that are within --cnv-merge-distance of one another and have the same CN and MCN assignments are combined, along with any intervening neglibible segments, on a trial basis, into a single segment that is recalled and rescored. If the merged segment receives the same CN and MCN as its constituent non-neglible pieces, with a sufficiently high quality score, the original segments are replaced with the merged segment. The merged segment might be further merged with other initial or merged segments to either side. Merging proceeds until there are not any segment pairs that meet the merging criteria.