Telomere-to-telomere assembly of diploid chromosomes with Verkko

The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on manual integration of ultra-long Oxford Nanopore sequencing reads with a high-resolution assembly graph built from long, accurate Pa...

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Bibliographic Details
Published in:Nature biotechnology 2023-10, Vol.41 (10), p.1474-1482
Main Authors: Rautiainen, Mikko, Nurk, Sergey, Walenz, Brian P., Logsdon, Glennis A., Porubsky, David, Rhie, Arang, Eichler, Evan E., Phillippy, Adam M., Koren, Sergey
Format: Article
Language:English
Subjects:
631/114/2785/2302
631/208/514/1948
631/208/728
Agriculture
Assembling
Assembly
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Chromosomes
Diploids
Diploidy
Genome, Human - genetics
Genomes
Genomics - methods
Graph theory
Haplotypes
High-Throughput Nucleotide Sequencing - methods
Humans
Life Sciences
Nucleotide sequence
Sequence Analysis, DNA - methods
Telomere - genetics
Telomeres
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Summary:The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on manual integration of ultra-long Oxford Nanopore sequencing reads with a high-resolution assembly graph built from long, accurate PacBio high-fidelity reads. We have improved and automated this strategy in Verkko, an iterative, graph-based pipeline for assembling complete, diploid genomes. Verkko begins with a multiplex de Bruijn graph built from long, accurate reads and progressively simplifies this graph by integrating ultra-long reads and haplotype-specific markers. The result is a phased, diploid assembly of both haplotypes, with many chromosomes automatically assembled from telomere to telomere. Running Verkko on the HG002 human genome resulted in 20 of 46 diploid chromosomes assembled without gaps at 99.9997% accuracy. The complete assembly of diploid genomes is a critical step towards the construction of comprehensive pangenome databases and chromosome-scale comparative genomics. Integration of long and ultra-long reads results in improved phased, diploid assemblies.
ISSN:1087-0156
1546-1696
1546-1696
DOI:10.1038/s41587-023-01662-6