Does anyone know if BWA is handling masked sequences properly? I'm having a problem where I find some reads aligned to genome gaps. I have tried converting the N's to X's, but still encountering the same problem.
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This is a known issue. Ambiguous bases are converted to random sequences. If you use bwa-short, the XN tag tells you how many "N" in the alignment. If you use bwasw, you do not get this information, but you may find such hits by checking you reference genome.
The chance of a good alignment arising from random hits is vanishingly small. Just ignore those hits.
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