I have RNA-Seq data from a "control" cell line and the same cell line in which a an oncogenic transformation was induced (3 samples of each).
I want to look for SNVs that are characteristic of the transformed cells. I have followed the GATK best practices for calling variants in RNA-Seq, which includes alignment with STAR 2-pass followed by GATK splitNtrim (splits reads into exon segments).
I now want to perform the variant calling step. I believe that using GATK's HaplotypeCaller (as detailed in the workflow) is inappropriate because, first, I have a mixture of cells with possibly different somatic mutations, and second, it does not compare between the control and transformed lines. Tools such as MuTect seem to be more appropriate. Nevertheless, I don't know if such can be used on RNA-Seq data. For example, the read depth may be highly variable between the "control" and "tumor" samples, because there are large differences in gene expression between the two.
Does any of you know of any tools that can use RNA-Seq as input for calling variants in the tumor vs. normal setting?
Thank you Gil