I am looking to identify DNA-level variations from a matched tumor-normal WES data. Specifically, I just want to know the variations in the tumor sample in relate to the reference genome, not the normal sample.
I have noticed two possible approaches here:
- Simply use a germline-variant caller to call variants from the tumor sample, or
- Call, separately, germline variations between reference and normal, and somatic variations between tumor and normal. The two callsets are then combined.
I'm well aware of the ploidy issues surrounding tumor samples and thus somatic callers are always separate algorithms. However, which is the better approach for my purpose?
Thanks in advance!