Haplotype-Resolved Assembly for Synthetic Long Reads Using a Trio-Binning Strategy

Abstract

ABSTRACTThe accuracy and completeness of genome haplotyping are crucial for characterizing the relationship between human disease susceptibility and genetic variations, especially for the heterozygous variations. However, most of current variations are unphased genotypes, and the construction of long-range haplotypes remains challenging. We introduced a de novo haplotype-resolved assembly tool, HAST that exports two haplotypes of a diploid species for synthetic long reads with trio binning. It generates parental distinguishing k-mer libraries, partitions reads from the offspring according to the unique markers, and individually assembles them to resolve the haplotyping problem. Based on the stLFR co-barcoding data of an Asian as well as his parental massive parallel sequencing data, we utilized HAST to recover both haplotypes with a scaffold N50 of >11 Mb and an assembly accuracy of 99.99995% (Q63). The complete and accurate employment of long-range haplotyping information provided sub-chromosome level phase blocks (N50 ∼13 Mb) with 99.6% precision and 94.1% recall on average. We suggest that the accurate and efficient approach accomplishes the regeneration of the haplotype chromosomes with trio binning, thus promoting the determination of haplotype phase, the heterosis of crossbreeding, and the formation of autopolyploid and allopolyploid.