Saphyr Study Is First to Analyze Cancer Regulation at Level of Single DNA Molecules, Opens Promising New Avenue of Cancer Research
Publication on novel Saphyr based method to analyze DNA methylation in cancer genomes enables new field of cancer research and drug target discovery
Bionano Genomics
February 02, 2021 08:00 ET
SAN DIEGO, Feb. 02, 2021 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO), announced today the publication of a study that measured DNA methylation, the chemical modification of the DNA that controls gene regulation, of the various regions regulating cancer genes on single DNA molecules. The study led by Dr. Yuval Ebenstein at the Tel Aviv University found that optical genome mapping (OGM) with Bionano’s Saphyr system combined with a custom labeling method developed by the scientists was capable of analyzing regulatory regions that work together to turn cancer genes on and off over distances of hundreds of thousands of basepairs. The ability to measure these relationships on single DNA molecules is something that was previously impossible. Only Saphyr can detect these long-distance connections in methylation profiles because it’s the only technology that can generate such long-range, single molecule data at high throughput and coverage.
While most of the important information in our genome is encoded in the sequence and the structural organization of the sequence, the regulation of genes is partially registered through chemical labels attached to the DNA. These chemical labels, called DNA methylation, can turn genes on and off at specific time points and in certain tissues. A normal cell can only become cancerous and grow excessively by making multiple changes to the genome and the way it is regulated. These changes include single nucleotide variations, structural variations and changes to DNA methylation patterns that can happen to the actual cancer gene, to the promoter region that switches the gene on and off, or to enhancer regions that can be hundreds of thousands of basepairs removed from the cancer gene. Studying these methylation patterns has been difficult or impossible because current methods only allow you to measure values averaged over dozens or hundreds of cells. To fully understand how cancer genes are turned on and off, it is important to measure the methylation status of a gene, its promoter, and its enhancers on individual, single molecules, which is impossible with short-read or long-read sequencing because their read lengths are insufficient.
The study by Dr. Ebenstein is the first to systematically analyze more than one hundred thousand promoter-enhancer pairs up to 200,000 basepairs apart, on millions of single molecules. This large dataset enabled them to correctly distinguish between normal and tumor cells with an error rate smaller than 1%.
Yuval Ebenstein, PhD, commented: “Long methylation reads at such high coverage just never existed before, mostly because Saphyr produces the highest fraction of the longest reads compared to any other platform. This dataset allows us to analyze long range information on the single-molecule level, which opens up a whole new avenue for complex disease specific epigenetic biomarkers. This study can be dramatic for early cancer diagnostics where the normal and cancer cells have a very similar genetic background but the extreme changes in enhancer methylation distinguish the cancer cells. This data may for the first time allow us to discover new biomarkers and point to novel drug targets in places of the genome where no one has looked before.”
Erik Holmlin, PhD, CEO of Bionano Genomics commented: “While Bionano Genomics is laser focused on bringing comprehensive, whole genome structural variation detection to the clinic, scientists around the world are pushing the boundaries of what our single molecule analysis system Saphyr can do. Dr. Ebenstein’s team has developed a novel application of our technology that contributes to solving unique scientific questions. The epigenetic regulation of cancer genes through DNA methylation of its promoters and enhancers has been difficult or impossible to study with current methods that are limited by short read lengths. We are excited about the possibilities for discoveries of novel diagnostics and treatments for cancer that this application enables.”
The publication is available at https://www.biorxiv.org/content/10.1101/2021.01.28.428654v1