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Dovetail Genomics Launches First Commercial Service Based on Short-Read Sequencing-Assembly Protocol


NEW YORK (GenomeWeb) – Dovetail Genomics has launched a Genome Assembly service based on its DNA sequencing-assembly protocol, which the firm claims will provide higher-quality genome assemblies based on short-read next-generation sequencing data than existing technologies.

The service, which is the company's first commercial offering for the market, uses its proprietary library construction approach and accompanying scaffolding software. Dovetail combines its library prep and analysis method with existing shotgun NGS assemblies to produce accurate genome assemblies that offer as much as a 200x increase in scaffold contiguity, according to the company. Its technology features a method of constructing so-called Chicago libraries that's based on in vitro chromatin assembly. 

These libraries contain inserts that span all distances up to the maximum fragment size of the input DNA. Following sequencing and initial de novo assembly, Dovetail uses its proprietary HiRise software to scaffold contigs from the preassembled sequences using the mate-pair libraries. The protocol was developed in the laboratory of Richard Green, the company's founder, at the University of California, Santa Cruz. The company presented the technology publicly for the first time at this year's Plant and Animal Genomes Conference.

Dovetail is charging variable pricing for its genome assembly service with customers able to select what portions of the service meet their requirements and needs. Todd Dickinson, Dovetail's CEO, told GenomeWeb, that prices range from under $10,000 a project to upwards of $40,000. The company offers several options for obtaining a draft assembly. The most comprehensive is for Dovetail to produce and sequence both the Chicago library as well as Illumina shotgun libraries to approximately 80x sequencing coverage, and then generate the assemblies.

Alternatively, customers can provide their existing draft assemblies that have a minimum contiguity of 30 kb, and Dovetail will use its technology to improve the assembly. The company's technology can work with sequence data from various instruments but it is currently targeting data from Illumina machines. Current turnaround time for projects is 6-10 weeks.

Dovetail's genome assembly service is the first of several planned commercial offerings from the company. As part of a five-year roadmap, Dickinson said that the company will roll out a series of targeted applications based on its technology starting with one for identifying structural variations, which should be available from its product menu in the next couple of months. The company will also eventually offer applications for metagenomics and phasing among other plans, he added.

Earlier this year, Dovetail launched a beta to give members of the community a chance to field test its technology. Dickinson said that the company worked on about 45 projects as part of the beta. In addition to testing, the company also spent the intervening months refining its workflow, setting up a facility and putting standard operating procedures in place, and recruiting staff with experience in sequencing and library building in preparation for the commercial launch. Dovetail also purchased a HiSeq 2500 and MiSeq and it has contracts in place with unnamed external sequencing vendors to handle seasons of increased demand, he said. The company has also made improvements to its protocol so that it can generate assemblies from less than a microgram of DNA, Green told GenomeWeb. However, the company does ask customers to provide at least 1-2 micrograms of material as a precaution. — By way of comparison, for at least one of the betas, the tester provided about 5.5 micrograms of high quality DNA.

Among the list of beta testers were evolutionary research groups from the University of Konstanz and the University of Copenhagen who tested the Dovetail technology in projects focused on the genomes of cichlids and vampire bats respectively. Researchers from each group that spoke to GenomeWeb for this story both said the Dovetail technology provided much better assemblies for their respective genomes of interest compared to what they'd been able to generate for a fraction of the cost associated with using existing sequencing approaches.

The group at the University of Konstanz group led by Axel Meyer, professor of zoology and evolutionary biology, among other projects, researches the evolution of cichlids exploring specifically genes associated with phenotypic traits in the different species found in lakes in Nicaragua and Africa. Meyer is part of the cichlid genome consortium that published five African cichlid genomes in Nature last year. For the Dovetail beta, he told GenomeWeb, the researchers worked with data from cichlids found in the greater Nicaraguan lakes. They used the company's technology to assemble an improved reference genome than what they were previously able to accomplish with existing approaches offered by Illumina and Roche.

Not only was the assembly size of Dovetail genome better, it was also much less fragmented, Meyer said. Their initial cichlid reference which was created using a combination of sequences and insert libraries from Illumina and Roche had about 6636 contigs and an N50 size of 1.21 megabases. For Dovetail's protocol, the assembly used about 4074 contigs and the N50 size in this case was 3.23Mb. 

Meanwhile Tom Gilbert, professor of paleogenomics at the University of Copenhagen's Natural History Museum of Denmark, and his team used Dovetail's technology to generate a reference assembly of the common vampire bat. His group studies the species to try to understand the genetic basis for the evolution of blood-feeding diets. Like the cichlid study, Gilbert's group used the Dovetail technology to improve an existing draft assembly generated by BGI. Compared to the earlier vampire assembly which had an N50 of 5.5Mb and an N90 of 0.9Mb, the final Dovetail assembly had an N50 of 27Mb and N90 of 9.5Mb. Essentially, it generates improved scaffolds, he told GenomeWeb. It makes it possible to combine longer lines of contigs, which is useful for obtaining better synteny information or exploring structural variation, he said.

Besides improved scaffolding, the cost of the Dovetail's technology is also a factor in its favor. Both Meyer and Gilbert told GenomeWeb that their labs paid significantly less for assemblies generated with Dovetail's technology than they'd previously paid for their existing assemblies. Meyer's lab for instance had spent upwards of $100,000 over several years on sequencing and assembling its existing cichlid reference compared to around $10,000 — beta pricing — it spent to get a high quality reference from Dovetail, he said.

The low cost makes it good fit for labs in smaller universities like Konstanz who might find that it's more cost-effective to use services like Dovetail's instead of running it on their own in house facilities, he noted. Furthermore, the approach also calls for less sequencing — only a few short insert libraries and Dovetail's Chicago libraries — to get a good quality reference genome, Gilbert told GenomeWeb. One possible drawback, Meyer noted, is the requirement for high quality sample material — getting longer fragments requires higher molecular weight DNA — which could limit the technology's use in projects that have to work with degraded samples and or very limited quantities of DNA.