WGS CN data and functional partial deletions


I have a question regarding the new CN data released with the DepMap release 24Q2. It appears that functional partial gene deletions are not detected in the WGS/WES derived CN data (OmicsAbsoluteCNGene.csv).

For example, the cell line NCI-H1650 has a partial deletion of the PTEN gene that is described as a functional deletion [reference]. The CN call for PTEN based on WGS resulted in an absolute copy number of 1 (with ploidy 2.20) and the functional deletion is therefore not detected with the standard CN annotation. However, when looking at the segmented data (OmicsAbsoluteCNSegmentsProfile.csv), a segment (chr10:87963620-87979619) which partially covers the PTEN coding sequence has a copy number of 0 (figure).

Do you have some thoughts on why the difference occurs and the best approach to identify these partial deletions?

Figure: Coverage of the PTEN gene by the segment chr10:87963620-87979619.

Many thanks!


Hi Daphne,

Thanks for reaching out.

In this case, this segment was surrounded by two segments that have CN=2. Since we use a weighted average approach to transform the segment-level data to gene-level matrix, the gene-level copy number was averaged to 1.

It is challenging to summarize CN on the gene level, as CNV segmentation is not aware of gene boundaries. We are currently revising this approach, but in the meantime, I’d recommend referring to the segment-level data for more granular information.

Hope this helps,

Hi Simone,

Thanks for the clear explanation!