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Oxford Nanopore Technologies announced recently that it has two products capable of sequencing DNA by reading the chemical bases in a DNA molecule directly, as it is threaded through a nanoscopic hole in a protein. The U.K.-based company will begin selling a simple, disposable, portable $900 DNA-reading device, and a more comprehensive desktop model, by the end of the year.

If Oxford Nanopore’s technology can do what the company claims, it will be “a total game-changer,” says Jeffery Schloss, director for technology development at the National Human Genome Research Institute, part of the National Institutes of Health.

The technology relies on the fact that a DNA base, or a combination of bases on a DNA strand, creates a characteristic disruption in a current as it passes through the nanopore. Electrodes measure the change in current flow as DNA molecules are fed through protein nanopores; an electrical gradient drives the DNA through the pore, while molecular “controllers” attached to the molecules mechanically slow them down so that their electrical signals may be recorded.

This approach has two important advantages.

First, the system is compact and doesn’t require a supply of expensive reagents. That means sequencing can come out of the lab, making it useful for personalized medicine or for use in resource-poor clinics. Indeed, the disposable sequencer the company is about to introduce is the size of a USB memory stick.

Second, the technology reads much longer stretches of DNA than other rapid sequencing approaches, which means it has the potential to be better at spotting important “structural variants” related to disease. These variants occur when a whole segment of chromosome is moved, inverted, duplicated, or otherwise changed. When DNA is chopped into shorter stretches to be sequenced and then put back together on a computer, it is easier to miss, or misinterpret, such variants.

The best way to identify variants is still to use conventional sequencing methods, which are highly accurate but also expensive and slow. Other rapid sequencers released in recent years are fast and inexpensive, but Schloss believes Oxford Nanopore’s may have an edge when it comes to spotting structural variants.

Better structural information could be useful for personalized medicine. Among other things, it could identify cases of translocation, a chromosomal abnormality in which large stretches of DNA break away from the chromosome where they belong and reattach someplace else. These mutations can cause cancer and other diseases.

The company’s portable nanopore sequencers could be used in the field—for example, to quickly identify or sequence a new strain of bacteria. A spokesperson for Oxford Nanopore says the portable sequencers might be used to monitor wound care in hospitals or to aid in on-site monitoring of agricultural sites for food safety.

At a research conference last week in Marco Island, Florida, Oxford Nanopore reported continuously sequencing 100,000-base stretches of DNA in the lab—sequences about 10 to 100 times longer than any other company has read. Pacific Biosciences’ newest commercial machines are capable of sequencing up to 3,000 bases at once, says the company’s director of product management, Edwin Hauw.

But nanopore sequencing could go way beyond this. In theory, the only limit on the length the system can sequence is researchers’ ability to prepare the inherently fragile samples. Human chromosomes encompass a million or so DNA bases.

The Oxford Nanopore system so far has a raw error rate of 4 percent. In the short term this might be improved by sequencing the same strand of DNA multiple times, threading it back and forth through the pore. However, the company says that in the coming months it will make improvements to the nanopore and the algorithms associated with the DNA analysis that will also reduce the error rate. 

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Credit: Oxford Nanopore

Tagged: Biomedicine, DNA, sequencing, personalized medicine, Oxford Nanopore Technologies

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