Vanderbilt University Medical Center (VUMC) has formed a subsidiary focused on applying its genomic and bioinformatics data toward advancing the discovery and development of new drugs and diagnostics.
VUMC said the new subsidiary, Nashville Biosciences, seeks to support the institution’s research as well as work with biopharmas and other life science companies to accelerate their development of new treatments by leveraging data contained within the medical center’s genomics and health information technology resources.
Those resources include VUMC’s BioVU biorepository of de-identified DNA samples. BioVU contains more than 250,000 DNA samples extracted over the last decade from discarded blood collected during routine clinical testing, coupled with 2.8 million de-identified patient records, the medical center said—adding that participation in BioVU is strictly voluntary.
The new subsidiary can also draw upon analytical methods developed for mining DNA datasets. VUMC cited the development of phenome-wide association studies or PheWAS designed to analyze many phenotypes compared to a single genetic variant, or other attribute.
Researchers led by Josh Denny, M.D., VP of personalized medicine, originally developed the method using electronic medical record (EMR) data from EMR-linked in BioVU. The original PheWAS catalog contains PheWAS results for 3,144 single-nucleotide polymorphisms (SNPs) present in the NHGRI GWAS Catalog as of April 17, 2012, in 13,835 European-ancestry individuals from five sites of the Electronic Medical Records and Genomics (eMERGE) network. A total of 1,358 EMR-derived phenotypes were analyzed for each SNP. This PheWAS replicated 66% (51/77) of sufficiently powered prior GWAS associations, and 210/751 of all prior GWAS associations.
PheWAS can also be applied to other richly phenotyped sets, VUMC says.
“Partnering with the pharmaceutical and broader life sciences industry through Nashville Biosciences will enable VUMC to expand and support its mission of advancing translational and precision medicine,” Nashville Biosciences founder and COO Leeland Ekstrom, Ph.D., said in a statement.
Added Dan Roden, M.D., VUMC’s SVP for personalized medicine: “The creation of Nashville Biosciences will dramatically accelerate our ability to work with pharmaceutical and other partners to advance human health by accelerating rational drug and diagnostics development and use.”
Seeking Genotype-Phenotype Associations
In a study published last year, researchers from VUMC and Vanderbilt University School of Medicine detailed the creation and activity of an incubator designed to support a diverse pipeline of drug indication-finding projects by leveraging human genetic data from BioVU.
The Accelerating Drug Development and Repurposing Incubator (ADDRI) is a multidisciplinary think-tank of experts in various therapeutic areas within both basic and clinical science, as well as experts in legal, business, and other operational domains. ADDRI seeks to validate candidate genotype-phenotype associations that are identified based on known biology, literature associations, and clinical attractiveness.
Key factors in exploring these associations, according to the researchers, include:
- Identifying existing published results related to the gene, protein, SNP, and phenotype, including GWAS data and established databases for gene/phenotype associations such as OMIM, ClinVar, and MalaCards.
- Analyzing data on the known and predicted functional impact of prioritized SNPs by using SIFT, PolyPhen, and Combined Annotation-Dependent Depletion
- Evaluating the plausibility by analyzing the known and predicted involvement of the SNP, gene, and protein in the potential underlying biologic pathway of the phenotype.
- Assessing peer-reviewed biomedical literature related to the SNP, gene, protein, and effects of modulation of the protein via genetic or pharmacologic methods to gauge and summarize the volume, strength, and nature of published evidence.
- Assessing the utility of known or predicted compounds for modulating the protein of interest; and
- Gauging the potential clinical impact and treatment efficacy for the condition.
“This program will extend our capacity to effectively direct a diverse pipeline of repurposing candidates, ensure the scientific validity and commercial viability of targets, and provide a mechanism for efficiently applying intellectual and other institutional resources toward drug repurposing,” corresponding author Jill Pulley, MBA, of the Vanderbilt Institute for Clinical and Translational Research, and colleagues, wrote of ADDRI.
Their study, “Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics,” was published in ASSAY and Drug Development Technologies, a journal published by Clinical OMICs publisher Mary Ann Liebert Inc.
Before the official launch of Nashville Biosciences, VUMC said, it has leveraged its resources in partnerships with biopharma giants Pfizer and Celgene, as well as precision medicine developers Goldfinch Bio and Population Bio. The medical center teamed up with the companies to discover new treatments in disease areas of interest for each partner—among efforts that VUMC said will be transitioned to Nashville Biosciences.
Added Gordon Bernard, MD, VUMC’s EVP for research: “We’ve only just started to scratch the surface of what is possible with genomics and informatics resources that can be coalesced for research in a comprehensive academic medical center.”