Benzinga | Oct 14, 2021 08:02AM EDT

Bionano Genomics Announces Study Shows The Combination Of OGM And NGS With Linked-Reads Detects Significantly More Clinically Relevant Variants Resulting In Higher Success Rates For Resolving Previously Unclassified Subjects In Genetic Disease Research

Bionano Genomics, Inc. (BNGO), developer of the Saphyr(r) system that uses optical genome mapping (OGM) for the detection and analysis of structural variants (SVs), today announced the publication of a study in which OGM and next-generation sequencing (NGS) with linked-reads were used together to resolve genetic diseases that were previously unclassified after evaluation by whole-exome sequencing (WES) alone. This study, from the University of California, San Francisco (UCSF) and Children's Hospital Oakland (now UCSF Benioff Children's Hospital Oakland) and appearing in the September 23, 2021 peer-reviewed issue of Nature Publishing Journal of Genomic Medicine, shows the benefit of combining OGM with short-read sequencing for improved detection of clinically relevant variants in genetic disease research.



The study's authors, Shieh, et al., describe their Full-Genome Analysis (FGA) approach with automated analysis using NGS linked-read sequencing and OGM to evaluate a full spectrum of genetic variants found in inherited genetic diseases. FGA identified structural variants and small variants with an increase in detection capability of 40% (20 of 50 cases). The number of resolved cases attributable to SVs was notable in the study, as 50% of exome-negative cases (four of eight cases) were solved by identifying an SV or rearrangement. The authors also identified candidate variants in another 60% (18 of 30 cases) for future follow-up.

In one specific case, the authors found a rare 32?kb heterozygous de novo intronic duplication within the NHEJ1 gene that was not detected by standard microarray analysis because it was small and intronic. It had also escaped detection in copy number variants called from short-read, whole genome sequencing (WGS) data but was easily identified with their FGA method using OGM.

The findings reinforce that the combination of OGM and NGS used in the FGA method detects and localizes SVs such as duplications missed by WGS, and can quickly identify translocations and phase variants across long distances. For individuals with undiagnosed conditions, these two technologies encompass what is currently provided by the combination of chromosome analysis -- karyotyping, microarray testing and short-read WGS. FGA provides information beyond current assays and results in higher resolution genome maps that can be used for future studies.

As observed in the study, Bionano's Saphyr(r) system, which can detect all classes of SVs, such as insertions, deletions, inversions, duplications, translocations and copy number variations, complemented NGS. Accordingly, when used together, they can provide the clinical research community with the ability to see the entire genome and identify a more comprehensive set of genetic variants to diagnose rare diseases accurately.

Erik Holmlin, PhD, CEO of Bionano Genomics, commented, "This study's results go beyond just reinforcing the power of OGM -- it shows us how we can significantly impact people's lives by combining NGS and OGM in genome analysis to find answers. Fifty percent of the participants in this study had clinically relevant variants hidden in their genomes that WES alone had not uncovered. OGM, together with a linked-read assay using NGS, revealed key answers for these participants. We believe there is tremendous potential in using OGM together with NGS to understand disease from the very beginning of any study. Congratulations to Dr. Shieh and his team on this tremendous progress."

This publication is available at https://www.nature.com/articles/s41525-021-00241-5