11 months ago by
San Francisco, CA
Yes, CNVkit and other segmentation-based copy number callers struggle to accurately detect CNVs in constitutional samples. Using default settings, a single-exon CNV won't show up with the segmenters currently available (though you could in theory use the 'spread' and 'log2' columns in a pooled reference as the basis for a Z-test of each exon in your capture -- this is not yet supported directly).
If your sequencing data are high quality then you can subdivide the targets and antitargets more finely, as your other comment mentions, though this can result in more noise as well. Then if you've managed to increase the sensitivity of CNVkit on your data and are now seeing poor specificity, you can reduce false positives with the
segmetrics --ci and
call --filter ci commands.