NuProbe Global, a global molecular diagnostics company based in Shanghai, China and Houston, Texas, and Bionano Genomics, based in San Diego, California, have entered into a procurement and collaboration agreement, where NuProbe will integrate their Quantitative Amplicon Sequencing (QASeq) and Blocker Displacement Amplification (BDA) technologies with Bionano’s Saphyr system for research and product development in the fields of reproductive health and oncology liquid biopsies.

“The Bionano OGM system provides direct and unambiguous identification and characterization of large-scale DNA structural variants without complex bioinformatics. NuProbe’s BDA technology helps zoom in on low frequency variants with single-base resolution. This seems a great match to provide genomics and clinical researchers with the gamut of DNA variant information from large to small,” says George Church, professor of genetics at Harvard Medical School and a member of NuProbe’s Scientific Advisory Board.

Bionano’s Saphyr single-molecule optical mapping system uses single-molecule fluorescent markers to detect structural variants and identify the specific genome structure. The technology allows researchers and clinicians to identify genetic diseases caused by structural variants and develop therapies. Compared with traditional structural variant detection methods, such as karyotyping and FISH, Saphyr has the advantages of high resolution, whole-genome coverage, user-friendly workflow and intuitive result presentation, and can accurately detect balanced translocations and inversions, which are hard-to-detect structural variants.

“Saphyr is the leading platform capable of detecting structural variants present at low fraction in complex cancer samples,” says Erik Holmlin, CEO of Bionano Genomics. “NuProbe’s technology allows for the detection of low-abundance point mutations. Combined, they can provide researchers and clinicians with a more complete picture of the mutational burden of a tumor sample than any single technology can by itself. We are excited to see how this combination of our strengths will allow NuProbe to develop a superior product for genome analysis in reproductive health and oncology.”

QASeq is an amplicon sequencing technology that uses unique molecular identifiers (UMIs) and multiplexed library construction technology to achieve accurate detection and quantitation of mutations and copy number variations in FFPE tissue, fresh or frozen tissue or cfDNA samples from blood. QASeq has high conversion yield and sensitivity. When coupled with NuProbe’s proprietary bioinformatics, it enables rapid development of custom NGS products with higher limit of detection in CNV detection of tumor cells than traditional methods such as FISH.

“Bionano’s single-molecule optical mapping system can detect structural variants and provide breakpoint information of DNA fusions at a resolution of 5kb,” says David Yu Zhang, PhD, head of Innovation at NuProbe USA. “When combining it with NuProbe’s QASeq technology, we can obtain accurate DNA breakpoint location information, thus facilitating the research in gene fusion. “

BDA is a novel PCR-based mutation enrichment technology that can effectively reduce wild-type amplification efficiency and enlarge low-frequency mutation signals through innovative thermodynamic design in PCR amplification cycle. BDA enables detecting SNVs with variant allele frequency (VAF) as low as 0.01%. BDA can be widely applied to various molecular diagnostic platforms including PCR, first-generation capillary sequencing, second-generation high-throughput sequencing, third-generation single-molecule sequencing, and nucleic acid mass spectrometry. Also, BDA technology can effectively detect low-abundance mutations at the RNA level.

“Currently, in both reproductive health and oncology, some variants cannot be detected by NGS, such as structural variants >1kb, and some gene fusions are under-detected,” says Yingshuang Chai, CEO of NuProbe. ” Bionano is a new cytogenetic technology that we have evaluated as a powerful complement to existing NGS technologies. Combined with our QASeq and BDA technologies, it can effectively help clinicians to identify the location and causes of disease.””