Say I have two VCFs with 100 samples in each file. Each VCF was joint-called separately and now I want to merge the variant calls.
Do I need to left-align the INDELs in the merged VCF? I've used bcftools norm in the past and got odd results. It seems that vt is a better tool for this.
Is left-aligning only useful for common variants? If I'm interested in rare variants (<0.5% AF) would left-alignment actually matter?
Thanks
Here's an example of bcftools norm
Original VCF
chr7 157009949 . AGCGGCGGCGGCG AGCGGCGGCGGCGGCGGCG,A,AGCGGCGGCGGCGGCGGCGGCG,AGCGGCGGCG,AGCGGCGGCGGCGGCGGCGGCGGCG,AGCGGCGGCGGCGGCG
Left-Aligned VCF (with multiallelics split into biallelic calls)
chr7 157009949 . A AGCGGCGGCG
chr7 157009949 . A AGCGGCGGCGGCG
chr7 157009949 . A AGCGGCG
chr7 157009949 . A AGCG
chr7 157009949 . A AGCGGCGGCGGCGGCG
chr7 157009949 . AGCG A
chr7 157009949 . AGCGGCG A
chr7 157009949 . AGCGGCGGCGGCG A
Suppose one of your VCF files has a non-left-aligned insertion, represented as REF=AG, ALT=AGT, starting at position 99999, and another file has an insertion represented as REF=G, ALT=GT, starting at position 100000. If you don't left-align, these may not be recognized as the same variant, and downstream analysis will suffer.
Thanks for the clear answer. Do you recommend vt or bcftools for normalization?
Either will work (as long as you aren't using a very old bcftools version). The latest bcftools should be faster, especially if compiled with "libdeflate".
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Hello,
could you please give an example of an "odd result" of
bcftools norm?fin swimmer
Edited the main query above.