Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33288906.
- Also identified by DOI 10.1038/s41587-020-0719-5 and PMC identifier 7954704.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Human genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing<sup>1,2</sup> with continuous long-read or high-fidelity<sup>3</sup> sequencing data. Employing this strategy, we produced a completely phased de novo genome assembly for each haplotype of an individual of Puerto Rican descent (HG00733) in the absence of parental data. The assemblies are accurate (quality value > 40) and highly contiguous (contig N50 > 23 Mbp) with low switch error rates (0.17%), providing fully phased single-nucleotide variants, indels and structural variants. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified 154 regions that are preferential sites of contig breaks, irrespective of sequencing technology or phasing algorithms.
Medical subject headings
- Genome, Human
- High-Throughput Nucleotide Sequencing
- Parents
- Sequence Analysis, DNA
- Single-Cell Analysis