After running Varscan and Mutect on a set of 10 patients (tumor / normal comparison), I have run through a pipeline of false-positive filtering. When I look at my resulting Ts/Tv ratio (by manual calculation, snpEff summary file, SnpSift tstv calculation or GATK VariantEval), it is quite low for human whole genome sequence data (1.3-1.6). I have read all I can find here and in papers about the expected ratio, and how a low ratio could denote a great deal of false positives.
I ran Varscan with relatively lax parameters for calling somatic mutations (5 reads in N, 8 in T, but strand bias filtered), however I thought Mutect would call a confident set. Both SNP callers end up with a low Ts/Tv. My question is, can I chalk this result up to false positives (which is okay with me, I wanted a sensitive not specific call set), or could it be a problem with the BAM alignment? I suppose a poorly aligned BAM would lead to false positives too, but any insight or information would be greatly appreciated.