Nabsys, a DNA technology startup, showed off today its solid-state gene sequencing machine at the Advances in Genome Biology and Technology conference in Marco Island, Florida. The company says that later this year it will begin selling its machine, which will allow researchers to determine the structural organization of long stretches of DNA. This differs from most existing sequencing methods, which read DNA in short snippets that are later stitched together by software. The new system will, at first, complement existing methods, but it could eventually offer cheaper and faster sequencing than other approaches.
Understanding the overall order of DNA sequence on a chromosome is important for studying disease and treating patients, but this big picture can be difficult to get because of the short-snippet approach of most sequencing. Because these methods cannot always figure out how to arrange long repetitive sequences, they can fail to recognize missing sequences, additional sequences, or repeated sequences, all of which can lead to disease.
“If you encounter these [repetitive] regions in traditional sequencing where DNA is chopped up, it is very hard to know how many times it was repeated,” says Jens Gundlach, a physicist who heads the University of Washington’s Nanopore Physics Lab.
Oncology, in particular, could benefit from Nabsys’s approach because the genomic changes that occur in cancer cells often include large, structural rearrangements. “In a tumor, you need to characterize the mixture of [genetic variation] in your sample at different length scales,” says Barrett Bready, CEO of Nabsys.
There are other technologies that can provide the kind of long-range mapping information that Nabsys promises. Opgen, for example, has developed a technique that visually measures the length of DNA in between known sequences (see “A Map of the Whole Genome Tracks Outbreaks”), but the optical technique can’t provide the resolution that the Nabsys technology promises. Groups such as Oxford Nanopore (see “Nanopore Sequencing”), which introduced its technology a year ago at the same conference, and Gundlach’s lab are developing nanopore technologies as another method for getting long sequences, but so far no nanopore technology has made it to the market. These systems use a biological pore as the site of DNA analysis, which limits the speed at which DNA can be read.
Nabsys’s technology also passes DNA through a pore, but instead of the protein pore approach that Oxford Nanopore and others are taking, Nabsys uses a pore cut into a solid-state chip. According to the journal Biotechniques, Oxford Nanopore’s system can process DNA at a maximum rate of 400 bases per second. Nabsys claims its system can read up to a million nucleotides per second. Such speed could be critical in clinical settings, where fast diagnoses are needed to make treatment choices.
The Providence, Rhode Island-based company uses premade short stretches of DNA called probes that can be detected on Nabsys’s chip when bound to a single molecule of DNA under study. Each probe consists of a short combination of the four DNA bases that will stick to matching sections of the larger DNA under study. The Nabsys technology detects where a probe is bound by watching an electric current change as the DNA complex snakes through a pore on the solid-state chip. Thousands of probes of different combinations of letters would be needed to sequence the whole genome. But by combining the position of many probes of different DNA sequences, the company can re-create a map of long stretches of DNA.
“The Nabsys technology isn’t a DNA reader per se,” says Gundlach. “It’s a more complex process to look for certain regions on a piece of DNA,” he says, that is “complementary to the existing sequencing techniques and helps them in providing contiguity.”
The company will initially focus on being a complementary technology to existing next-generation sequencers, but its technology can provide full-sequence information if more probes are used to analyze a sample.