Verkko

Verkko automates telomere-to-telomere assembly of complete, diploid genomes by iteratively integrating long, accurate PacBio high-fidelity reads with ultra-long Oxford Nanopore sequencing reads through a graph-based pipeline.

Key Features:

• Hybrid assembly: Combines PacBio HiFi and Oxford Nanopore ultra-long reads for complete genome assembly.
• Graph-based approach: Builds a multiplex de Bruijn graph from long, accurate reads and progressively simplifies it by integrating ultra-long reads and haplotype-specific markers.
• Phased diploid output: Produces a phased, diploid assembly of both haplotypes with many chromosomes automatically assembled from telomere to telomere.
• Verkko2 enhancements: 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.
• Acrocentric and sex chromosome resolution: Assembles all regions of a diploid human genome including the short arms of acrocentric chromosomes and both sex chromosomes.

Scientific Applications:

• Complete diploid genome assembly: Enables automated assembly of complete diploid human genomes with high accuracy, achieving 99.9997% accuracy on the HG002 genome with 20 of 46 chromosomes assembled without gaps.
• Large-scale pangenomics: Enables telomere-to-telomere comparative genomics and pangenomics at scale across population panels, assembling an average of 39 of 46 complete chromosomes across 19 human genomes.
• Chromosome-scale comparative genomics: Supports the construction of comprehensive pangenome databases and chromosome-scale comparative genomics by providing complete, phased diploid assemblies.

Methodology:

Verkko begins with a multiplex de Bruijn graph built from long, accurate PacBio HiFi reads and progressively simplifies this graph by integrating ultra-long Oxford Nanopore reads and haplotype-specific markers. Verkko2 adds proximity-ligation-based haplotype phasing and scaffolding, a more efficient read correction algorithm, and improved repeat resolution and gap closing.