Nabsys uses HD-mapping platform to produce first long-range, non-optical maps of whole human genomes

Genomics firm Nabsys has produced the first long-range, non-optical maps of whole human genomes using its high-definition electronic HD-mapping™ platform. The maps have subsequently been used for genome-wide analysis of structural variants, DNA changes typically larger than several hundred base pairs which are implicated in a wide array of diseases.

Structural variants are often difficult to identify (or "call") using traditional sequencing techniques, as the short reads generated often do not span the entire variant. While long-range optical mapping approaches enable long reads, their low resolution limits the ability to call variants. The ability to read longer segments of DNA at a higher resolution with the Nabsys HD-Mapping platform facilitates calling and analysis of variants over a wide range of sizes.

"Genomic variation has clinical implications at all scales, from single-base changes to aneuploidy, and every size in between," said Nabsys Founder and CEO Barrett Bready , M.D. "As a scientific community, we're currently quite good at systematically analyzing the lower third, or smaller scale, variations. However, the analysis of the larger two thirds is as much art as science. The Nabsys HD-mapping platform now allows for the systematic analysis of variants across the rest of the spectrum."

Analysis of the Nabsys data demonstrates that this electronic mapping approach is extremely powerful for analysis of structural variation over a wide range of sizes. Electronic detection allows Nabsys to call with high sensitivity and specificity both large structural variants and smaller variants, the size of short reads from next-generation sequencing platforms. Creating the link between short-read data and long-range information will enable elucidation of the full range of genomic variation.

"Our electronic mapping platform allows us to combine several desirable technical attributes that are not achievable with other technologies," added Nabsys Chief Technology Officer John Oliver, Ph.D. "Specifically, our maps are generated by analyzing very long DNA molecules, on the order of 100,000 base pairs. The DNA travels through semiconductor-based detectors at high velocity, over one million base pairs per second, while obtaining resolution superior to optical methods. With this approach, researchers can now look across whole genomes and analyze structural variation with the same sensitivity and specificity found in SNP analysis. This opens up the rest of the spectrum of genomic variation to systematic analysis."

This project was conducted in collaboration with the Genome in a Bottle (GIAB) consortium, a public-private-academic consortium hosted by the National Institute of Standards and Technology (NIST) to develop the technical infrastructure to enable translation of whole human genome analysis to clinical practice. Nabsys results were presented during a consortium meeting on September 15, 2016 , held at the NIST campus in Gaithersburg MD.

Nabsys structural variant calls are available to members of the GIAB consortium. Raw data are available to Nabsys collaborators.