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Bwa Combined Reference Vs Sequential Alignment

Hi,

I am currently developing a pipeline for novel viral detection and I am using BWA for filtering the mapped sequnces.

I recognized during my tests that I have a different number of unmapped reads after I align my sample against the whole genome once, in contrast to if I align each chromosome seperately and pipe the output.

Is this causing BWA heuristically concept, that I get a different number of mapped sequences by using the same references? Is this normal?

What is better, to align chromosome by chromosome or to align the whole genome at once?

Would be pelased if anyone could help.

bwa

1 answer

A related question on Biostar would be Exome sequencing: masking the non-genic sequences?

The answer to your question is that in general you should always align against the full reference genome that your samples could come from.

For example as mentioned above even though the process attempts to capture the exome a lot of reads could come from other regions and if you'd mask these regions during alignment you could be mistakenly assign the reads to exons.

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