Merging CNV data with Mutation data and running on MutSigCV

Question

[sara.younes]

I am trying to find the most significant altered genes and I was thinking of using only 1 tool for significance test which is MutSigCV instead of MutSigCV for mutation data and GISTIC for CNV data. I know that MutSigCV works with short indels but can I merge my CNV segmented data in the MAF file (Divide each long CNV into regions) and input them to MutSigCV or this wouldn't work? Can MutSigCV work with long insertions or deletions? What is the maximum indel length that MutSigCV can operate on?

Answer 1

[Sean Davis]

MutSigCV will work on indels that are called by a somatic variant caller. The size of such variants is usually on the order of 1-10 base pairs. Unfortunately, that means that CNVs need to be treated somewhat separately. Determining the most significant genes, then, involves some additional work to integrate the CNV analysis with MutSigCV, other assays on the samples, and additional biological knowledge from public databases.

[sara.younes]

I tried to run GISTIC and then MutsigCV then integrate significant genes from output of both then do my downstream analysis but the problem is a gene can sometimes be insignificant interms of mutation and insignificant in terms of CNV but when this information is grouped together the gene becomes significant. that's why I wanted only to use one tool. I was thinking of dividing the CNV into small indels and adding it to the MAF file. do you think this is would lead to reasonable results?

[Sean Davis]

I do not think that adding small indels to the MAF file will be useful or lead to meaningful results. I agree that figuring out what is "significant" can be challenging and I do not know of a nice "tool" that does exactly what you want in a general sense.