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Does MuTect work with reduced bam files produced by Reduce Reads?
Currently MuTect does not perform well on Reduce Read bams. The problem is that in the act of reducing, a lot of sequencing noise is also reduced and thus our noise model is not well powered. Similarly in the normal, low allele fraction events are reduced right out of the BAMs.
Conceptually, it's something that we would like to support but the trick will be to balance the compression against the loss of information. Right now, it will work if you set the reduction parameters very strictly... but at that point the BAMs is barely reduced thus defeating the purpose!