Meraculous-2D: Haplotype-sensitive Assembly of Highly Heterozygous genomes

TL;DR

Meraculous-2D is a genome assembly method that accurately reconstructs both haplotypes in highly heterozygous diploid genomes by preserving allelic variation, overcoming limitations of traditional bubble resolution approaches.

Contribution

It introduces Meraculous-2D, an improved algorithm that maintains haplotype information during assembly, enabling accurate reconstruction of highly heterozygous genomes.

Findings

Successfully assembled highly heterozygous genomes with preserved haplotypes.

Produced more complete and less fragmented assemblies compared to traditional methods.

Reported phased haplotype variant information during assembly.

Abstract

While many short read assemblers attempt to simplify the de Brujin graph by identifying and resolving variant-induced bubbles to produce a haploid mosaic result, this approach is only viable when variants are relatively rare and the bubbles are well defined in a graph context. We observed that diploid genomes with very high levels of heterozygosity fail to display well-resolved bubble structures in a typical assembly graph and thus result in highly fragmented and incomplete assemblies. Here we present an enhancement of Meraculous2 algorithm, called Meraculous-2D, which preserves haplotypes across variant sites and generates accurate assembly of highly heterozygous diploid genomes. Preserving and taking advantage of the allelic variation throughout the assembly process allows reconstructing both haplomes at once, without the need to pick arbitrary paths through bubble structures. We also enhanced the original diploidy resolution method of Meraculous2 to maintain and report phased haplotype variant information.