A new way to study SVs

Dr. Erik Holmlin, president and CEO of Bionano, commented, “Large genomic rearrangements are increasingly understood as drivers of serious human health conditions. Sequencing solutions based on short reads do not capture these SVs with sufficient sensitivity and specificity to enable comprehensive studies of their biological and clinical significance, and even long read sequencing does not overcome these limitations. Results of these four studies demonstrate the ability of Bionano’s next-generation mapping to accurately detect large SVs, many of which have critical clinical implications with the potential to meaningfully improve patient outcomes.”

According to Holmlin, “Bionano’s next-generation mapping is a technique that generates ultra-long-range information on how genomes are organized. NGM combines proprietary NanoChannel arrays with optical mapping to image extremely long, high molecular weight DNA in its most native state. NGM provides essential genomic information no other solution can provide to help advance greater understanding of genome biology. NGM is useful for researchers in the genomics space, because the information allows them to see changes in genome structure that is invisible to sequencing methods. NGM is very complementary to industry standard next-generation sequencing (NGS).”

“Bionano’s NGM technology comprehensively detects large SVs, including both heterozygous and homozygous variants, with unrivaled sensitivity and precision in the industry,” Holmlin continues. “NGM is primarily used in two respects: to generate reference quality genomes—combining long-range info from Bionano’s NGM and short-range form sequencing to assembly the most complete reference quality genome—and to search for and identify large SVs. As a stand-alone tool, NGM with Bionano enables the detection of SVs, many of which are associated with human disease as well as complex traits in plants and animals.”

Holmlin says BioNano facilitates high-resolution de-novo mapping without the need for a reference genome. “Bionano is most excited about identifying large SVs that are well known in cytogenomics and cause genetic disorders, including playing an important role in cancer. NGM is necessary to better understand disease and develop new treatments.”

“For example, in types of leukemias, translocations gives rise to an active increase in enzymes associated with the cancer by identifying the SVs associated with increase of this enzyme. These SVs can be hard to find, but they are lurking under the surface in diseases and cancer, and can be identified using NGM with Saphyr,” notes Holmlin. “Furthermore, Saphyr allows researchers to assess genomes on population scale, not just one genome, like our first-generation system called Irys. Saphyr makes translational studies possible that can lead to diagnostics.”

“At the AGBT meeting in February, we launched the Saphyr System, Bionano’s newest and most advanced system for genome mapping. Saphyr is a high-speed, high-throughput platform that delivers unparalleled sensitivity and specificity in SV detection, genome assembly contiguities up to 100-fold longer than those of short-read sequence assemblies and the structural accuracy to correct sequencing-based errors,” Holmlin tells DDNews. “Saphyr is an incredibly forward mapping approach, with increased throughput by a solid factor of 10. This increase in throughput translates to reduction in cost, uses fewer consumables and less time, [providing] more cost-effective genome analysis. Our current focus is increasing the adoption of NGM with Saphyr in research institutes for improved genomic findings and translational research results.

“Two studies in particular [show this at the] Garvan Institute. Research from genomics leader Vanessa Hayes concludes that prostate cancer is a disease of SVs—in her research published in Oncotarget, using NGM she found hundreds of SVs missed by Illumina sequencing. Furthermore, not only were they missed but, of the ones found, half have oncogenic potential. The mapping technique proves to be very powerful and could help identify patients for clinical trials.”

“[With the second study, with] Eric Vilain at UCLA in transition to D.C. at Children’s National Health, the research in patients with inherited diseases using the undiagnosed disease network showed that mapping of 11 patients explained two patients’ diseases, which is incredible,” says Holmlin. “These 11 patients have gone through every test and turned out negative, but mapping showed at least two patients. NGM is shining a light on parts of the genome that have been invisible previously. Furthermore, with a third patient who was diagnosed via muscle biopsy, it was shown that NGM could also get the same diagnosis, using mapping on a blood sample. This mapping technique is proving to be very useful and have clinical utility.”

Asked if NGM could someday overtake NGS, Holmlin replies, “Structural variations are often missed by sequence-level technologies alone, because these technologies cannot capture or represent the full structure of genomic information. As a complementary tool to other genomic technologies like NGS, NGM with Bionano can be integrated with sequence-generated assemblies to create reference genomes and contiguous hybrid scaffolds that reveal the highly informative native structure of the chromosome, and provide the additional ability to verify, correct and enhance a genome assembly. We continue to see studies showing that the combination of sequencing technologies plus Bionano NGM data creates the most contiguous and accurate assemblies possible.”