Assembly of complete diploid phased chromosomes from draft genome sequences

Abstract

De novo genome assembly is essential for genomic research. High-quality genomes assembled into phased pseudomolecules are challenging to produce and often contain assembly errors caused by repeats, heterozygosity, or the chosen assembly strategy. Although algorithms exist that produce partially phased assemblies, haploid draft assemblies that may lack biological information remain favored because they are easier to generate and use. We developed HaploSync, a suite of tools that produces fully phased, chromosome-scale diploid genome assemblies and performs extensive quality control to limit assembly artifacts. HaploSync uses a genetic map and/or the genome of a closely related species to guide the scaffolding of a diploid assembly into phased pseudomolecules for each chromosome. It compares alternative haplotypes to identify and correct misassemblies independent of a reference, fills assembly gaps with un-placed sequences, and resolves collapsed homozygous regions. In a series of plant, fungal, and animal kingdom case studies, we demonstrate that HaploSync increases the assembly contiguity of phased chromosomes, improves completeness by filling gaps, corrects scaffolding, and correctly phases highly heterozygous, complex regions.