Dear All,

I would like some suggestions from the experts. I have been using VarScan past one year and have been very helpful in fishing out high confident calls for my samples. I would like to know ask that I see the coverage parameter of tumor is less than that of normal in varscan 2 default mode. Is there a way to compare the output of varscan with that of Mutect? Usually I use mutect for low sensitive calls. which has higher coverage reads for tumor (14 default) and for normal it is less (8 reads) for calling a somatic variant. So if I want to compare the variants that are called by both varscan and mutect (though the statistical model is different in both) but keeping coverage paramater same can I use VarScan2 with tumor coverage reads 14 and normal coverage reads 8 which will be default of Mutect. I usually take the combination of variants provided by both VarScan and Mutect since my experimental idea is not rare variants but more of finding somatic variants that are in tumor and then passing on to tumor clones. Also my tumor are polyclonal so now I want to find the clonality and I want to use same parameters in both tools so that I can use the VAF values from both tools. I have two tumors (low and high grade) with their corresponding matched normal. I would like some suggestion. Did anyone try to make similar read coverage calls earlier with both tools? How viable is it? Usually VarScan2 have normal reads coverage more but if is it advisable to make the tumor reads coverage more than normal in VarScan2 exactly the similar parameter to that of Mutect and make the call? I would like to have some guidance from the experts before I do this.

Regards