Variant calling in phased assemblies

Question

[veronica.mixao]

Hello,

I want to do variant calling in a diploid organism using a phased genome as a reference. Therefore, in the reference we have both chromosomes represented. For variant calling should I consider this genome as a diploid (as it is) or a haploid (as the reference has the 2 homolog chromosomes)? What do you think?

Thanks in advance!

Answer 1

[colindaven]

Good question (10X genomics data?). This is similar to the current situation with extra haplotypes in the human assembly. GRCh38 is now ~45 GBp of sequence, whereas without alternative haplotypes the human genome is around 3 GBp.

The only haplotype-aware mapper I know of is bwa mem, and AFAIK this is only for certain genomes. I would be happy to find our more.

I am not convinced that the appropriate approach is short read mapping on a diploid/haplotype containing genome.

Other approaches are graph based, see https://github.com/DecodeGenetics/graphtyper

and https://github.com/vgteam/vg