Researchers from the National Institutes of Health (NIH) released a software tool designed to assemble gapless genomes. The tool, Verkko, was developed for telomere-to-telomere assembly of PacBio HiFi and Oxford Nanopore reads.
Verkko was created during the Telomere-to-Telomere (T2T) consortium’s recent work on the first complete human genome. Around 8-10% of the human genome was missing and generated by the T2T’s efforts. Due to many of the complex regions, manual integration was required of ultra-long reads from Oxford Nanopore sequencers along with an assembly graph built from PacBio’s
accurate high-fidelity reads. Much of this manual work took several years to complete with skilled teams of scientists dedicated to the task.
Researchers from the T2T built Verkko in order to automate and improve this process. A recent publication in Nature Biotechnology explains how Verkko builds these complete/gapless genomes.
The process begins by using Canu to correct errors in the HiFi reads. Then a multiplex de Bruijn graph is built using MBG, and the Oxford Nanopore reads are aligned to the graph using GraphAligner. This gradually resolves loops and tangles beginning with the HiFi reads, followed up with the aligned Oxford Nanopore reads. Lastly, contig consensus sequences are created with Canu's consensus module.
The end result is a phased, diploid assembly containing both haplotypes that include telomere to telomere assembled chromosomes. When Verkko was run on the HG002 human genome, the results showed that 20 out of 46 chromosomes were assembled without gaps.
Human and non-human genomes have been tested with Verkko, showing a rapid and precise assembly of whole chromosomes. The tool will now allow researchers to get a better understanding of the diversity across the entire genome and how genetic variation exists in the highly repetitive regions of DNA.
What was once a difficult and year-long process for researchers will now only take a couple of days. Creators like NHGRI senior investigator Adam Phillippy hope that the availability of this new software will make genome assemblies more affordable and routine.
Verkko was created during the Telomere-to-Telomere (T2T) consortium’s recent work on the first complete human genome. Around 8-10% of the human genome was missing and generated by the T2T’s efforts. Due to many of the complex regions, manual integration was required of ultra-long reads from Oxford Nanopore sequencers along with an assembly graph built from PacBio’s
accurate high-fidelity reads. Much of this manual work took several years to complete with skilled teams of scientists dedicated to the task.
Researchers from the T2T built Verkko in order to automate and improve this process. A recent publication in Nature Biotechnology explains how Verkko builds these complete/gapless genomes.
The process begins by using Canu to correct errors in the HiFi reads. Then a multiplex de Bruijn graph is built using MBG, and the Oxford Nanopore reads are aligned to the graph using GraphAligner. This gradually resolves loops and tangles beginning with the HiFi reads, followed up with the aligned Oxford Nanopore reads. Lastly, contig consensus sequences are created with Canu's consensus module.
The end result is a phased, diploid assembly containing both haplotypes that include telomere to telomere assembled chromosomes. When Verkko was run on the HG002 human genome, the results showed that 20 out of 46 chromosomes were assembled without gaps.
Human and non-human genomes have been tested with Verkko, showing a rapid and precise assembly of whole chromosomes. The tool will now allow researchers to get a better understanding of the diversity across the entire genome and how genetic variation exists in the highly repetitive regions of DNA.
What was once a difficult and year-long process for researchers will now only take a couple of days. Creators like NHGRI senior investigator Adam Phillippy hope that the availability of this new software will make genome assemblies more affordable and routine.
