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Nabsys Develops 'Positional Sequencing' Tech for Assembly, Whole-Genome Mapping, Targeted Sequencing

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By Monica Heger

Nabsys is aiming to provide an "inherently targeted" nanodetector sequencing platform that can offer de novo whole-genome sequencing and assembly, whole-genome mapping, and targeted sequencing.

The platform, based on technology dubbed "positional sequencing," will be especially suited for identifying structural variation, helping to assemble repetitive regions, and parsing heterogeneous samples, company officials told In Sequence this week.

The technology uses a nanodetector system that detects probes hybridized to DNA, providing both sequence and positional information from large stretches of single molecules of DNA.

Recently, Nabsys hired industry veteran Stan Rose as chief commercial officer as part of its strategy to commercialize the system (IS 1/10/2011). Rose was previously CEO of NimbleGen and led the PCR businesses at PerkinElmer and Applied Biosystems.

Company officials declined to disclose any metrics on accuracy, speed, throughput, or cost, as well as its timeline for commercialization, but said they plan to present some details of the system at next month's Advances in Genome Biology and Technology meeting.

Rose told In Sequence that the platform is in many ways analogous to PCR. PCR involves an instrument, key reagents that drive the reaction, and then customers choose primers based on the regions they want to target, he said. Similarly, Nabsys's platform is based on solid-state nanodetectors, a proprietary set of reagents that drive the reaction, and probes that define the regions to be sequenced, which can be customized by the customer to ask specific questions.

Rose explained that users first isolate the DNA using any standard method, and then hybridize the probes. After that, the molecule is incubated with a reaction mixture and added to the instrument.

"So there's no library prep," he said, and "no special approach to isolating DNA."

Once the DNA is loaded into the platform, it threads through the nanodetectors at a speed of 1 million bases per second per detector. The company is not yet disclosing how many detectors are on each chip or how many chips are on each machine, but CEO Barrett Bready said that throughput is high, even when compared to the throughput that can be generated by sequencing-by-synthesis machines.

The number and length of probes a user employs depends on the application. Nabsys will be designing probe kits for whole-genome sequencing, whole-genome mapping, as well as a number of undisclosed targeted applications, Rose said.

"There are a series of applications for which we can provide everything the user needs, but at the same time, the customer will have the opportunity to experiment," Rose said. Users can design their own probes based on the application or question asked.

While Nabsys' positional sequencing approach is "inherently targeted," said Rose, it can also be used for whole-genome sequencing and de novo assembly, or even in tandem with short-read sequencing platforms.

For a targeted application, a user may need as few as several probes, while for de novo whole-genome sequencing, upwards of a few thousand probes will be needed. The company is not disclosing how long the probes will be, but Rose said they will be "nothing that's challenging to synthesize."

According to Rose, data analysis is much less complex than on current platforms because the system does not rely on optical imaging and it simultaneously gathers sequence information and location information. In addition, the company has developed its own algorithms for the system, which allows for "whole genome sequences that can be analyzed on a laptop, not some massive computer cluster."

Currently, data from the platform is sent to a laptop as it is generated, but Rose said that the company is still deciding whether it will provide a computer as part of the commercial platform.

Two areas that the company expects to target are oncology and agricultural biology. In oncology, the platform will be especially useful for detecting structural variations and characterizing heterogeneity, Rose said, while in the ag-bio field, he said that there has been a lot of interest from companies sequencing crops because plant genomes often contain a lot of repetitive regions.

Due to the nature of Nabsys's technology, which can anchor sequence fragments to positions in the genome, resolving highly repetitive regions is not as difficult as with short-read sequencing-by-synthesis technologies, he said.

Additionally, Rose said, the platform could be of interest to anyone doing whole-genome sequencing or mapping, anyone using fluorescence in situ hybridization to detect structural variations, or anyone "pushing the limits of PCR."

The "inherently targeted nature of it means that it makes a lot of sense in the clinic," he said.

Nabsys' platform could also be complementary to short-read sequencing platforms, aiding in de novo assembly.

The platform could compete with FISH and PCR, and will also likely compete with sequencing platforms as well as DNA mapping platforms, such as those being developed by BioNano Genomics and OpGen.

BioNano Genomics,formerly BioNanomatrix, is developing a nanochannel platform to visualize single molecules of DNA and expects its first applications to be in de novo assembly and structural variant analysis (IS 6/21/2011). OpGen has been using its optical mapping technology to help with de novo assembly and to correct errors in finished genomes (IS 7/5/2011).

According to Bready, Nabsys' technology differs from optical mapping systems because it provides not just mapping, but "positional sequencing" of targets to whatever size the user specifies. And, because it is electronic, and not based on optics, "the resolution is better" since it is not limited by diffraction.


Have topics you'd like to see covered by In Sequence? Contact the editor at mheger [at] genomeweb [.] com.

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