Haplotype-resolved assembly of diploid genomes without parental data

Routine haplotype-resolved genome assembly from single samples remains an unresolved problem. Here we describe an algorithm that combines PacBio HiFi reads and Hi-C chromatin interaction data to produce a haplotype-resolved assembly without the sequencing of parents. Applied to human and other vertebrate samples, our algorithm consistently outperforms existing single-sample assembly pipelines and generates assemblies of similar quality to the best pedigree-based assemblies. Haplotype-resolved genome assemblies are generated by combining HiFi reads with Hi-C long-range interactions.