By Julia Karow
OpGen is betting on structural variation detection in humans as an important niche for its optical genome mapping technology as the company scales up from microbial to mammal-size genomes.
Last week, the firm launched Genome-Builder, a new software tool to handle the increased data yield of the Argus Optical Mapping System that will visualize whole-genome maps and help with the assembly of sequence scaffolds. Along with it, the company will be offering higher-density disposable cards for its Argus system that will increase the amount of usable mapping data about three times, from 750 megabases to 1 gigabase per card today to about 2.5 gigabases. OpGen is also offering optical mapping services using these new products.
Combined with next-gen sequencing data, the new software and consumables kit will be especially useful for the de novo assembly of genomes from humans and other large organisms, according to Richard Moore, OpGen's CSO. For that application, the software will combine sequence scaffolds and optical restriction enzyme maps from OpGen's Argus system and create "super-scaffolds," resulting in assemblies that can reach almost the size of chromosome arms, he said. While assembling large genomes by conventional methods, such as BAC libraries and genetic markers, takes "many months," collecting data for the optical maps requires about a week for a human-sized genome, and the analysis about another week, he said.
OpGen has already tested the application in a yet-to-be-published demonstration project with BGI that the partners presented at several conferences earlier this year, where they assembled the goat genome (IS 7/5/2011). Since then, BGI has used the Genome-Builder software to help assemble a variety of organisms, Moore said.
In addition, in collaboration with the Wellcome Trust Sanger Institute, which recently received the Genome-Builder software, OpGen plans to assemble several genomes for the Genome Reference Consortium, he said (IS 8/30/2011).
Structural Variation Assays
Besides assisting with the assembly of DNA sequence data, OpGen is focusing on structural variation detection. In a recently published project, for example, scientists at the Walter Reed Army Institute of Research demonstrated that the Argus system, in combination with sequence data, could detect important structural rearrangements in the malaria genome that no other technique had been able to find. The authors wrote that using optical maps, they were able to produce "high-quality contigs" spanning the four genomes in six weeks for less than $1,000 per genome.
The scientists used OpGen's technology to produce optical maps of all 14 chromosomes of four malaria genomes. They found new copy number variations that may be related to drug resistance, virulence factors, and immune evasion.
Also, early next year, OpGen plans to launch a whole-chromosome de novo assembly application for the Argus platform, which will be "somewhat" independent of sequence data. "You can use [the assemblies] as screens for structural variations, either with or without sequence," Moore said, adding that the application will also be available as a service.
The assembly technology will be able to detect structural variations two kilobases or less in length that would be difficult to detect with either classical cytogenetic techniques, which are good at picking up larger variants, or next-gen sequencing, which is good at detecting smaller ones. "I think we will fill a nice, high-resolution niche in between," he said. Also, in contrast to comparative genomic hybridization, the technology will be able to pick up balanced events.
The company hopes to use the whole-genome application to build specific structural variation assays, both for inherited disease and cancer, initially for clinical research. It might be a while, though, before any clinical applications emerge.
"We're not ready for it now, mainly because I don't know exactly where the clinical assays are going to come from," Moore said. He added that much like CGH, the approach will likely remain in the clinical research setting "until it's very clear what exactly the clinical assays will be."
Have topics you'd like to see covered in In Sequence? Contact the editor at jkarow [at] genomeweb [.] com.