Benzinga | Nov 22, 2021 08:05AM EST

Bionano Genomics Announces Peer-Reviewed Publication From Johns Hopkins University Outlining A Stepwise Approach To The Adoption Of Optical Genome Mapping For Cancer Analysis

Bionano Genomics, Inc. (BNGO), provider of optical genome mapping (OGM) solutions on the Saphyr(r) system and the leading software for genomic data visualization, interpretation and reporting, today announced the publication of a study by Johns Hopkins University in the Journal of Clinical & Anatomic Pathology outlining a stepwise approach to adoption of OGM for cancer analysis in the cytogenetics lab.



"This publication is by an outstanding team at Johns Hopkins University and we believe it represents the type of foundational work needed to establish where OGM fits in the cancer analysis lab and the types of subjects and samples that should be analyzed with OGM," commented Dr. Alka Chaubey, chief medical officer of Bionano Genomics. "Knowing how different samples perform with OGM and the variants it detects can allow us to build a paradigm for working with OGM alongside other powerful tools in molecular pathology and cytogenomics as we push forward in our mission to transform the way the world sees the genome."

Conducted as a blinded comparison to a comprehensive collection of tools, this study compared results from OGM to those from whole-genome chromosomal microarrays (CMA) from Illumina, fluorescence in-situ hybridization (FISH) probes from Abbott, a targeted panel by next-generation sequencing (NGS) from Illumina, a gene fusion panel by gene expression on the nCounter from NanoString and traditional g-banding by karyotyping. The cohort comprised five different cancer subjects and multiple sample types: four leukemia/lymphoma subjects and one solid tumor subject across three bone marrow samples, one peripheral blood sample and one solid tumor sample (kidney tissue from a Wilm's tumor subject).

The findings by OGM were concordant with those obtained by CMA and NGS for copy number variants (CNVs) and FISH and karyotyping for balanced structural variations (SVs) such as inversions and translocations. Sensitivity compared to CMA was 96% (22/23 CNVs detected) excluding copy neutral loss of heterozygosity calls. Sensitivity compared to karyotyping and FISH was 100% (98/98 loci detected). OGM also revealed substantially more SVs than the traditional methods, including an additional 51 CNVs and 20 SVs. Of the variants revealed by OGM that were not detected by the standard methods, 52% involved genes and 7.7% of them involved known cancer genes. The other 48% were classified as variants of unknown significance (VOUSs). The authors point out that these VOUSs have the potential to play a role in further refining patient diagnosis and identifying novel proteins that could be therapeutic targets.

OGM was also used in the study to provide high resolution analysis of subjects with complex karyotypes exhibiting chromothripsis. Chromothripsis, or chromosome shattering, results in highly complex chromosomal structures that are typically very challenging to unravel by CMA, FISH and karyotyping. OGM provides a more comprehensive view across the genome that targeted methods like FISH cannot give and it has been shown to have a higher resolution than traditional methods as well. Compared to karyotyping, which has a resolution of 5 Mbp, OGM's resolution is 10,000 times higher and compared to CMA, OGM's resolution is 20-100 times higher, depending on the probe density used on the array. The authors used OGM to reveal and characterize chromothripsis (complex genome structures) in leukemia subjects with unprecedented scope and resolution, which they said can be extremely helpful in determining if there are druggable variants present, markers consistent with aggressive disease or disease that's treatment refractory.

The principal conclusions of this publication is that OGM provides an alternative workflow that provides valuable genomic information often with higher resolution than traditional methods without sacrificing sensitivity. OGM is complementary to methods like NGS, which reveal sequence variants, and provides an opportunity to simplify and consolidate workflows for SV analysis by using OGM as an alternative to CMA, FISH and karyotyping.

This publication is available at http://www.clinpathology.com/wp-content/uploads/2021/05/JCAP-6-117.pdf.