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bioRxiv · 10.1101/2024.12.20.629807

Verkko2: Integrating proximity ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding

Phillippy, A. M.·Koren, S.·Antipov, D.·Rautiainen, M.·Nurk, S.·Solar, S. J.·Walenz, B. P.
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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 semi-manual combination of long, accurate PacBio HiFi and ultra-long Oxford Nanopore 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 Verkko 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 and pangenomics, at scale.

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Phillippy, A. M., Koren, S., Antipov, D., Rautiainen, M., Nurk, S., Solar, S. J., Walenz, B. P.. 2024-12-22. Verkko2: Integrating proximity ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding. https://doi.org/10.1101/2024.12.20.629807

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