What is the goal of the TOPMed program?
The goal of the TOPMed program is to generate scientific resources that will improve the understanding of heart, lung, blood, and sleep disorders and advance precision medicine. Precision medicine is an emerging approach to disease prevention and treatment that considers the unique genes and environment of each patient.
The TOPMed program collects whole-genome sequencing and other -omics data. In biology, -omics refers to measurable differences or changes in biological molecules, such as genes, metabolites, proteins, and RNA. The program will integrate -omics data with molecular, behavioral, imaging, environmental, and clinical data to improve the prevention and treatment of heart, lung, blood, and sleep disorders.
The TOPMed program will specifically support the National Heart, Lung, and Blood Institute (NHLBI) Precision Medicine Activities. The program also complements the National Institutes of Health (NIH) Precision Medicine Initiative and All of Us Research Program, which will collect data from one million or more people to help study a range of health issues and diseases.
In 2016, the NHLBI released its Strategic Vision, which will guide the Institute’s research activities for the coming decade. The TOPMed program addresses many of the objectives, compelling questions, and critical challenges identified in the plan. For example, the program will leverage new technologies and advances in data science to promote discoveries about the earliest origins of diseases and individual differences in disease processes. The program will also leverage data from diverse participants in NHLBI’s population and epidemiology studies to enable research on health differences among populations.
- The Whole-Genome Sequencing (WGS) project, part of the TOPMed program, has sequenced over 90,000 genomes and aims to sequence more than 120,000.
- TOPMed program studies are collecting -omics data—RNA, gene, and metabolite profiles—in a subset of WGS project participants.
- The TOPMed program and WGS project are leveraging data from participants in NHLBI’s clinical and population studies.
- The NHLBI will fund efforts to accept additional samples, develop new ways to analyze -omics data, and present TOPMed program data in NIH’s Data Commons.
How does the TOPMed program contribute to scientific discoveries?
The TOPMed program will support research that furthers our understanding of heart, lung, blood, and sleep disorders. The program may lead to future scientific discoveries such as:
- Biomarkers that increase or decrease the risk of heart, lung, blood, and sleep disorders
- Interactions between the environment and genes that affect health
- Potential targets for new treatments
- New ways to define heart, lung, blood, and sleep disorders or subtypes of these disorders based on molecular signatures
- Targeted ways to develop and test personalized treatments in specific patients
- Advances in precision medicine to predict, prevent, diagnose, and treat heart, lung, blood, and sleep disorders
How does the TOPMed program work?
As the first step in the TOPMed program, the NHLBI established the WGS project. The WGS project is collecting whole-genome sequencing data for individuals who have well-defined clinical phenotypes and outcomes from earlier NHLBI-funded studies. The project has sequenced over 90,000 individual genomes and plans to sequence more than 120,000.
TOPMed researchers have started releasing WGS project data through the NIH Database of Genotypes and Phenotypes (dbGaP). Currently, there are over 30,000 whole genome sequences in dbGAP and approximately 45,000 more will be added to dbGaP in early 2018. The dbGaP was developed to archive and distribute data from studies that have investigated the interaction of genotype and phenotype, including all genome-wide association studies supported by the NIH.
The TOPMed program has started studies to collect -omics data in a subset of WGS project participants. Currently, these -omics studies are collecting RNA, gene, and metabolite profiles from individuals who participated in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA).
To help build -omics data, the NHLBI plans to review applications from researchers interested in contributing samples for the TOPMed WGS project and other -omics studies. The NHLBI is also supporting efforts to develop new ways to analyze -omics data. Data from NHLBI’s TOPMed program are one of three NIH-funded datasets included in a recently announced NIH Data Commons Pilot Phase, a part of the NIH Big Data to Knowledge (BD2K) program. Visit the NIH Common Fund’s NIH Data Commons Pilot Phase Explores Using the Cloud to Access and Share FAIR Biomedical Big Data page to learn more about the NIH Data Commons Pilot Phase, its awardees, and its test case data sets that include TOPMed program data. Read more about NHLBI precision medicine funding opportunities.
The TOPMed program consortium includes many centers, including the Data Coordination Center and the Informatics Research Center that serve the entire TOPMed program. As the TOPMed program grows, the NHLBI anticipates that other centers will join the consortium.