In whitepapers posted to the company’s website this week, Nabsys has provided new details into its next generation HD-Mapping™ platform. The platform provides a high-resolution electronic mapping instrument complete with solid-state nanochannel-based detectors and improved labelling chemistry with Hitachi High-Tech’s Human Chromosome Explorer™ (HCE) software as an analysis pipeline. The resulting platform provides a solution for high resolution human genome structural variation (SV) analysis with applications in disease research, clinical diagnostics, and pharmaceutical development, all while reducing complexity, consumable requirements, and associated costs.

A simple workflow is described that includes a sample preparation step to label long strands of DNA isolated from a human genome sample and use of a compact instrument the size of a desktop computer equipped with an electronic detection mechanism for reading solid-state nanochannels. The labeled DNA is passed through the nanochannels and changes in electrical resistance are detected at each label. The resultant reads contain information about the location of these labels on very long DNA molecules. Using Hitachi’s HCE analysis pipeline, reads are ultimately assembled and aligned in silico to a reference genome and any changes in alignment are called and reported as SVs.

The papers go on to claim that the combination of electronic detection, solid-state nanochannels, and optimized labelling protocols provide high signal-to-noise ratios and nearly eliminate crosstalk. The high resolution associated with electronic detection allows for the reliable detection of variants in the 300-1000bp range, as well as much larger structural variants.

“Every time I see the data, I get excited. I’m not aware of any other single-molecule bioanalytical system that achieves such a high signal-to-noise ratio, especially given the speed at which the molecules are moving through the nanochannels.” stated Nabsys CTO, John Oliver. “The accuracy and overall cost in using the platform represent a step change improvement to whole-genome mapping and provides a solution for researchers, clinical diagnostic test developers, and pharmaceutical scientists studying SVs within the human genome.”

Developed by Hitachi High-Tech, HCE is a whole-genome assembly and SV analysis pipeline that runs on Google Cloud. Results are visualized and reported through a browser-based interface.  When combined with HD-Mapping, it creates a system that detects and visualizes SV small enough to be complementary to short-read sequencing and those large enough to constitute chromosomal rearrangements. .

“HD-Mapping’s use of electronic detection eliminates the challenges of optical diffraction and allows for the detection of labels in closer proximity to one another. The higher resolution data is used by HCE to decrease the limit of detection for variants to the 300bp range while the long reads assemble nicely in HCE to elucidate large SV and repeats.”, stated Hitachi R&D lead, Tateo Nagai.

Hitachi will feature Nabsys at booth #833 during ASHG 2022 where Nabsys will showcase the HD-Mapping platform.

About Nabsys 2.0:

The Nabsys mission is to advance the understanding of disease, increase diagnostic yield, and improve patient outcomes by enabling routine, accurate, cost-effective analysis of genomic structural variation. Located in Providence, RI, Nabsys employs a growing interdisciplinary group of dedicated scientists, engineers, and other professionals committed to the advancement of genomic analysis.

About Hitachi:

Hitachi High-Tech Corporation, a wholly-owned subsidiary of Hitachi Ltd., headquartered in Tokyo, Japan, is engaged in activities in a broad range of business fields, including manufacture and sales of analytical systems, electron microscopes, in vitro diagnostic systems, and semiconductor manufacturing equipment, and providing high value-added solutions in fields of social & industrial infrastructures and mobility, etc.

Contact:

Nabsys 2.0

[email protected]