Graph reference genome and base-calling approach using imputed haplotypes

Abstract

The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a graph reference genome customized for a particular sample genome and utilizing the customized graph reference genome to determine final nucleotide-base calls for the sample genome. To illustrate, the disclosed systems can generate a customized graph reference genome including various paths representing imputed haplotypes corresponding to a particular genomic region. Additionally, or alternatively, the disclosed system can determine and compare direct and imputed nucleotide-base calls for a sample genome as a basis for generating final nucleotide-base calls. In some such cases, the disclosed system weights (and selects between) direct nucleotide-base calls and imputed nucleotide-base calls for genomic coordinates based on sequencing metrics corresponding to the direct nucleotide-base calls or based on the variability of the genomic regions comprising the genomic coordinates.