March 16, 2023
Our Senior Vice President of Science, Anthony Schmitt, PhD, joined Mendelspod host Theral Timpson to discuss 3D genomics, its current applications, and future opportunities arising from early successes in translational oncology. The podcast is available here (or search Mendelspod in your favorite podcast app).
What is 3D Genomics?
DNA sequencing produces a string of letters representing the bases of DNA, visualized in a linear fashion. Since DNA is more like a ball of spaghetti tightly packed within the nucleus of a cell, 3D genomics technologies like Hi-C and HiChIP can help researchers understand the three-dimensional arrangement of DNA bases and better study the effect of the genome’s structure on cellular function across a range of applications.
In his interview, Anthony describes the ways Arima Genomics is focused on advancing science, innovation, and health. We’ve built on our technological success in developing market-leading 3D genomics tools and actively partner with our customers to support scientific discovery across a range of basic and translational scientific research programs. We continue to innovate by providing tools to clinical and translational researchers and forming partnerships with the pharmaceutical and oncology communities. And increasingly, we are exploring new ways our technology can better support disease researchers, especially in cancer, as we become more focused on how our work can be translated into advances in the clinic.
The Many Uses of 3D Genomics
There are three main ways Arima Genomics customers use 3D genomics technologies today: genome assembly projects, to understand gene regulation as part of disease research, and to detect and understand structural variants, particularly for the purpose of understanding cancer biology.
Despite advances in next-generation sequencing technology, building high-quality, phased, chromosome-scale genome assemblies remains challenging. Arima Hi-C technology is being used by many large research consortia to build reference quality genomes including the Darwin Tree of Life project to help fill in the missing pieces in draft reference genomes and get to complete reference sequences.
As the structure of the genome plays a critical role in regulating gene expression, researchers use Arima Genomics technology to understand the chromosomal loops which bring regulatory elements into close proximity, which can alter their functions. We’ve seen this approach used in conjunction with other multi-omics technologies across many disease areas, both in bulk analysis and in single-cell studies, such as research focused on mapping the human brain at the single-cell level.
Structural variant detection
Structural variants are known to play a significant role in cancer. 3D genomics offers a consistent, hypothesis-free method for their detection. More than 95% of cancers have one or more somatic structural variants, and at least 30% of cancers have a known pathogenic structural variant. The growing knowledge base around the importance of gene fusions and other structural variants for patient stratification in cancer has fueled new translational and clinical opportunities for Arima Genomics.
Moving Towards the Clinic
The team at Arima Genomics has been working in close collaboration with several clinical partners to understand the clinical potential of 3D genomics technologies, especially in identifying potential therapeutic targets from cancer tumor samples deemed driver-negative by other next-generation sequencing-based assays. Working with these partners, the company has shared data at medical and scientific conferences, including 2022 presentations at the Association of Molecular Pathology annual meeting and the American Association for Cancer Research annual meeting.
Following initial successes, the company has recently signed partnership deals to smooth the path forward for the clinical adoption of 3D genomics. A recently announced partnership with Velsera will enable the broad adoption of Arima Genomics technology for the detection of gene fusions by clinical laboratories using Velsera’s Pierian Clinical Genomics Workspace.
Additionally, a recent agreement with Protean Biodiagnostics, a Florida-based CLIA-certified, CAP-accredited laboratory, will enable the development of a lab-developed test for the detection of gene fusions using Arima Genomics technology, and make it available for clinician orders. Also, leveraging the capabilities of Protean Biodiagnostics’ laboratory, the companies plan to utilize this test to support biopharmaceutical companies needing a partner in the prospective enrollment of patients in clinical trials which require a structural variant biomarker.