The NHLBI Trans-Omics for Precision Medicine (TOPMed) program will support the Institute’s larger precision medicine activities by collecting and coupling whole-genome sequencing (WGS) and other -omics data (e.g., DNA methylation signature, RNA expression profiles, metabolite profiles) with molecular, behavioral, imaging, environmental, and clinical data from studies focused on heart, lung, blood and sleep (HLBS) disorders.
The TOPMed program aims to:
- Collect and assemble -omics (RNASeq, methylation, metabolomics, epigenomics, and proteomics) data with WGS and clinical outcomes data across diverse populations including those traditionally underrepresented in research.
- Build a data commons repository that the scientific community can use for future research and to enable precision medicine.
- Stimulate systems medicine approaches that help organize data to ensure they are accessible and interpretable for health disease research.
- Promote discoveries about the fundamental mechanisms that underlie HLBS disorders.
Learn more about current TOPMed program activities, how NHLBI plans to grow the program, and the potential impact that the TOPMed program may have on research and clinical care.
Current TOPMed program activities
Establishing the WGS project was one of the first steps for the TOPMed program. The project’s goal is to collect WGS data for individuals who have well-defined clinical phenotypes and outcomes from earlier NHLBI-funded studies. Initially, the WGS project planned to sequence 20,000 genomes. The NHLBI has expanded the WGS project and it now will sequence about 62,000 individual genomes.
The TOPMed program is piloting studies to collect -omics data in a subset of WGS project participants. Currently, these pilot -omics studies are collecting RNA expression, DNA methylation, and metabolite profiles from individuals who participated in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA).
Currently, the TOPMed program consortium includes nine centers that support program activities such as data coordination, informatics research, whole-genome sequencing, RNA sequencing, and metabolite and methylation profiling. Two of these centers, the Data Coordination Center and the Informatics Research Center, serve the entire TOPMed program. As the TOPMed program grows, it is anticipated that other centers will join the consortium.
The National Center for Biotechnology Information (NCBI) will provide data repository and access service for the TOPMed program.
How NHLBI plans to grow its TOPMed program
In the coming years, NHLBI plans to expand the TOPMed program in several ways:
- Grow the WGS project even further, possibly sequencing over 100,000 individual genomes.
- Collect more -omics data.
- Develop and apply new methods for data access and analysis.
NHLBI is funding and pursuing the following efforts to build critical components of the TOPMed program.
- (PAR-16-021) NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01). Through this funding opportunity announcement (FOA), NHLBI plans to review and accept applications from researchers interested in contributing samples for TOPMed WGS and other -omics studies. Researchers interested in helping grow the TOPMed data commons can find more information about this announcement at the (PAR-16-021) NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01) FAQ.
- Centralized Omics REsource (CORE) for TOPMed. NHLBI has solicited proposals for multiple contract awards that will support the collection of WGS and other -omics data such as genome-wide DNA methylation, sequencing of expressed RNAs, and metabolite profiling.
- (RFA-HL-17-011) NHLBP TOPMed Program: Integrative Omics Approaches for Analysis of TOPMed Data (U01). Through this funding opportunity announcement (FOA), NHLBI plans to support the development of new methods for the analysis of -omics data in the TOPMed program. Awardees are expected to build and share their analytic tools with the TOPMed data commons. Visit (RFA-HL-17-011) NHLBP TOPMed Program: Integrative Omics Approaches for Analysis of TOPMed Data (U01) FAQ to see discussions about this closed funding announcement.
- NHLBI Genomics Portal (GenPort). NHLBI has released a Small Business Innovation Research (SBIR) award announcement to help develop, operate, and maintain the NHLBI GenPort data commons that will support the TOPMed program. Read NHLBI-HR-17-05-CS for more information.
- Trans-NIH collaborations. NHLBI is working with various National Institutes of Health (NIH) partners to share data and technical advice. Not only will these exchanges stimulate research, but they also will help NHLBI tackle short- and long-term technical issues related to sequencing standardization, large dataset storage and access, data commons and pilot cloud computing design, and how the TOPMed program may complement the NIH Precision Medicine Initiative Cohort Program.
The TOPMed program will provide initial -omics data for NHLBI precision medicine activities that will translate into more opportunities for the NHLBI community to pursue research that will further our understanding and improve the care of HLBS disorders. For example, the TOPMed program will support HLBS research to:
- Discover molecular biomarkers that increase or decrease the risk of HLBS disorders.
- Understand how environmental factors interact with genes to preserve health or contribute to our understanding of HLBS disorders.
- Identify potential drug targets.
- Redefine HLBS disorders or subtypes of these disorders based on molecular signatures instead of current tissue/organ-based approaches to medicine.
- Enable clinical trials to test treatments in a targeted way, such as in patients with specific genetic markers identified in the WGS project, to help develop personalized interventions.
- Accelerate systems medicine and emerging precision medicine to predict, prevent, diagnose, and treat HLBS disorders based on a patient’s unique genes, environment, and molecular signatures.