I have two haplotype-resolved genomes from a human individual and want to map long reads to them. My question is how to properly define the reference genome. Although I have both haplotypes, it seems that only one can typically be used as the reference for read mapping. One possible approach is to concatenate the two genomes into a single FASTA file, treating them as one combined reference, and then use minimap2 for alignment.
1 answer
I think concatenating H1 and H2 is an approach that is worth exploring. Unless there are large structural variants in one haplotype, or one is less complete than the other, I won't predict a massive increase in mapping rates (say +-2%), but it is worth trying. You need to be aware of the possibility of secondary alignments for every match, so remember to adjust your downstream filtration if necessary.
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