Verkko2 integrates proximity-ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding
- Dmitry Antipov1,4,
- Mikko Rautiainen2,4,
- Sergey Nurk3,
- Brian P. Walenz1,
- Steven J. Solar1,
- Adam M. Phillippy1 and
- Sergey Koren1
- 1Genome Informatics Section, Center for Genomics and Data Science Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Tukholmankatu 8, Biomedicum 2, Helsinki, Finland;
- 3Oxford Nanopore Technologies, Oxford OX4 4DQ, United Kingdom
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↵4 These authors contributed equally to this work.
Abstract
The Telomere-to-Telomere Consortium recently finished the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on the semimanual combination of long, accurate Pacific Biosciences (PacBio) HiFi and ultralong Oxford Nanopore Technologies sequencing reads. The Verkko assembler later automated this process, achieving complete assemblies for approximately half of the chromosomes in a diploid human genome. However, the first version of Verkko was computationally expensive and could not resolve all regions of a typical human genome. Here we present Verkko2, which implements a more efficient read correction algorithm, improves repeat resolution and gap closing, introduces proximity-ligation-based haplotype phasing and scaffolding, and adds support for multiple long-read data types. These enhancements allow Verkko2 to assemble all regions of a diploid human genome, including the short arms of the acrocentric chromosomes and both sex chromosomes. Together, these changes increase the number of telomere-to-telomere scaffolds by twofold, reduce runtime by fourfold, and improve assembly correctness. On a panel of 19 human genomes, Verkko2 assembles an average of 39 of 46 complete chromosomes as scaffolds, with 21 of these assembled as gapless contigs. Together, these improvements enable telomere-to-telomere comparative genomics and pangenomics, at scale.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.280383.124.
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Freely available online through the Genome Research Open Access option.
- Received December 20, 2024.
- Accepted May 12, 2025.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
