Telomere-to-telomere Assembly of Diploid Chromosomes with Verkko

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2023 Feb 16

PMID 36797493

Authors

Mikko Rautiainen

Sergey Nurk

Brian P Walenz

Glennis A Logsdon

David Porubsky

Arang Rhie

Evan E Eichler

Adam M Phillippy

Sergey Koren

Affiliations

Soon will be listed here.

Abstract

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.

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