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OpGen Prepping Optical Mapping System for Analysis of Human, Other Larger Genomes

By Tony Fong

NEW YORK (GenomeWeb News) – As OpGen intensifies the commercialization of its optical mapping technology, it is looking to expand its use to larger genomes, including humans, within the next year, its CEO said.

During the spring, the company launched its first instrument, called the Argus LS Optical Mapping System, globally. The system is targeted for simpler organisms, such as microbes, fungi, and yeast. If all goes as planned, in the third quarter of 2011, OpGen will launch the system for whole-genome sequence assembly and finishing for research on larger organisms, such as plants and animals, including humans, CEO Doug White told GenomeWeb Daily News.

Earlier this month, the Gaithersburg, Md.-based firm announced a collaboration with BGI to evaluate the platform's utility for de novo sequence finishing in larger organisms. It and BGI, OpGen said, had already used the technology to complete a study based on human genome data to successfully close gaps in existing sequence folds.

According to White, building out the Argus system for such an application encompasses mainly developing new algorithms, while the system and the chemistries will remain largely the same. The company has also developed restriction enzymes that are specific for mammals.

"One of the things that we are doing is developing the algorithms and the computational ability to enable that work to take our single-molecule restriction maps that are created and incorporate those and utilize those for the assembly and the gap closure," he said.

The Optical Mapping Technology was licensed from New York University and the University of Wisconsin, and OpGen has been developing it since its founding in 2002.

"We think there's a significant [opportunity] for the microbial market," White said, but, he added, the company targeted less complex genomes for the initial launch of the Argus system for practical reasons.

"Larger genomes are much more complicated and therefore a bit more onerous in terms of what's required, so the smaller genomes obviously were much simpler to work with," he explained.

OpGen's Optical Mapping Technology is a method of deciphering a genome's architecture by creating high-resolution, ordered, whole-genome restriction maps from single DNA molecules. In short, it works by taking DNA and then cutting the DNA at specific sequences by using restriction enzymes. The remaining DNA is stained with fluorescent dyes and images of the DNA are taken with a fluorescent microscope.

"So we get these very long lengths of DNA and are able to take these restriction cut sites. And by analyzing the images … we can put them back together and create a whole genome," or, in essence, a whole-genome restriction map, White said. "We make a fingerprint of the DNA, of the whole genome, that we can then put into our database and we can compare it with other isolates. We can do a whole variety of things."

Applications for the technology include strain typing and whole-genome sequence assembly. For strain typing, an optical map of the isolate of interest can be generated in about 24 hours, compared to the days or weeks that it would take with next-generation sequencing-based methods.

In addition, OpGen's technology "gives you much more distinguishing features and gives you the ability to identify down to the strain in an isolate level," unlike pulsed field gel electrophoresis, which White said is the gold standard method for separating DNA molecules.

One area that the company is focusing on is using the technology to arrive at high resolution analysis of an isolate and then using that data to compare the isolate with others that are associated with a public health outbreak. By doing so, researchers can then determine how similar or dissimilar the isolates are.

The technology also provides enough granularity to determine whether there are specific motifs within the isolate that may be associated with virulence or antibiotic resistance, White said.

For whole-genome sequence assembly and finishing, the Optical Mapping System is complementary to existing second- and forthcoming third-generation sequencing technologies, he said, in that it can provide a complete genome scaffold for contig alignment and orientation.

Using OpGen's MapSolver software, contigs generated by sequencers are mapped in silico "so that the contigs can be mapped back to the complete ordered optical map scaffold of DNA, giving researchers the ability to very rapidly orient the sequence data to help accelerate assembly and finishing," he said.

As a result, mutations, such as insertions, inversions, and deletions that may be missed with sequencing technologies can be found with the Optical Mapping System, and, similarly, contig misassemblies can be identified and corrected.

"The bottom line is that … we can help orient and align the contigs to our Optical Map scaffold that's been created," White said. "It also helps to identify where there are gaps, where there needs to be more sequencing done, and the location of where those gaps are within the context of the genome."

Since launching the Argus platform, which retails for about $300,000, in April, OpGen has been "very happy" with the response to it, and sales of the platform is driving projected revenues of $4 million for 2010, above what the company had originally budgeted, said White, whose appointment as CEO of the company was announced in June as the firm moved into full commercialization mode.

Revenues for 2011 are projected to double, he added.

OgGen recently closed on a $17 million Series B financing round to support marketing of the Argus LS platform and developing it for use on larger genomes. Since its founding, OpGen has raised more than $40 million.

Interest in the Argus LS has been especially keen in the international public health sector, as well as among researchers doing microbial sequencing, White said.

The Argus LS is a research-use only platform, and OpGen is in the process of adapting the Argus system for the clinical market by making it more user-friendly and less hand-on. The company is also in the midst of creating a database that would be required for use in a clinical setting.

OpGen anticipates launching the platform as an IVD product in 2013.

Next year, in addition to launching a system for larger genomes, the company plans to introduce an epidemiology service based on the existing platform.

"We think that there may be a significant opportunity in the hospital market for understanding outbreaks associated with nosocomial infections and trying to differentiate between nosocomial and community acquired infections," White said.

He anticipates the service being launched in the first half of 2011.

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