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Old 04-27-2009, 01:46 PM   #9
Nils Homer
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Location: Boston, MA, USA

Join Date: Nov 2008
Posts: 1,285

What I don't follow is if you align each end separately you will get the highest pairing fraction, since you are the very sensitive in this case (fewer constraints, in fact no constraints between each end). Furthermore, using one end to infer hits for the other can also increase sensitivity.

In my own experience, if one is sensitive enough, potentially false SVs (due to mapping) can be eliminated since by examining the secondary hits for each end, and seeing if there exists a pair of alignments for each end that fall within the expected insert size distribution that are not too much worse than the "best pair". Is this what you are talking about? If so, then we agree.

I would take exception to Novoalign being the most accurate, since this is conditional on sensitivity, as well as the many definitions of "accuracy".

Finally, I think you and I have a fundamental disagreement between what an aligner should do. I think it should return all hits for a given read that it can find (sensitivity), and let the user filter/choose the best alignment or alignment pair based on their experiment. I would prefer gapped smith-waterman, but this could vary based on experiment. Given this, I agree to disagree.

The aligner is but one step in the whole process, and everything shouldn't be lumped into the alignment algorithm.
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