NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01 - Clinical Trial Not Allowed) | PAR 25 447

Opportunity Information: Apply for PAR 25 447

The NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders opportunity (PAR-25-447) is a National Institutes of Health (NIH) Notice of Funding Opportunity that invites researchers to leverage the NHLBI-funded Trans-Omics for Precision Medicine (TOPMed) program to produce and integrate large-scale genetic and multi-omics datasets aimed at clarifying the biological mechanisms behind heart, lung, blood, and sleep (HLBS) disorders. The central emphasis is on generating omics-based phenotypes and integrated datasets that help connect genetic variation to molecular and cellular function, rather than stopping at statistical links between variants and disease traits. The NOFO is explicitly focused on research use and data generation and is labeled "Clinical Trial Not Allowed," meaning applications should not propose prospective interventional clinical trials as part of the work.

A defining feature of this announcement is that it uses the X01 activity code, which means no grant funding will be provided under the award. In practice, this kind of mechanism is often used to offer access to a resource, infrastructure, or coordinated program support rather than direct dollars to the applicant. Here, the resource is TOPMed itself, which is designed to support the creation of high-volume omics datasets that can be used by the broader community to accelerate discovery. Applicants should read the opportunity as a way to gain access to or participate in TOPMed-enabled data generation and integration efforts, with the expectation that the resulting datasets will become shared community assets.

The scientific goal is to push TOPMed from "genetic map" to "mechanism." In other words, the program is looking for work that helps explain how genetic factors actually drive disease biology, including identifying relevant genes, regulatory elements, pathways, cell types, molecular networks, and biological processes that link genotype to phenotype. This is aligned with modern functional genomics and systems biology, where the value comes from combining multiple layers of biology (for example, genome sequence plus transcriptomics, epigenomics, proteomics, metabolomics, and other omics measurements) and then interpreting them in a unified way. The NOFO also signals interest in the use of AI and machine learning methods where appropriate, particularly for integrating complex multi-modal datasets, discovering patterns, prioritizing mechanisms, and improving the interpretability and predictive power of mechanistic models.

Another major requirement is data sharing through NIH-designated controlled-access repositories. The genomic data and associated phenotype information generated through projects under this NOFO are expected to be deposited into controlled-access platforms such as the NIH database of Genotypes and Phenotypes (dbGaP) and NHLBI BioData Catalyst (BDC). Controlled-access repositories are used because human genomic and health-related phenotype data can be sensitive; access is managed through formal processes to protect participant privacy while still enabling broad scientific use. This requirement reflects NIH priorities around transparency, reusability, and building shared datasets that can support many downstream studies beyond the original project team.

In terms of who can apply, eligibility is broad and includes many types of U.S. organizations and governmental entities, along with certain non-U.S. entities. Eligible applicants listed include state, county, city or township, and special district governments; independent school districts; public and state-controlled universities; private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations other than small businesses; small businesses; and other organizations. The NOFO also highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities. This breadth suggests an intent to bring in diverse institutions and populations, which is particularly important for genomic and multi-omics research where representation affects both scientific validity and equity of future clinical translation.

Administratively, the opportunity is categorized as discretionary and uses the grant funding instrument type, but again, the key practical detail is that the X01 mechanism does not provide funds. The NOFO is associated with multiple CFDA numbers (93.233, 93.837, 93.838, 93.839, 93.840), reflecting NHLBI and related NIH program areas connected to heart, lung, and blood research. The original closing date is listed as May 8, 2028, indicating a long application window and the likelihood that NHLBI expects multiple submission cycles or ongoing participation as TOPMed evolves.

Overall, this opportunity is best understood as an access-to-resource and data-generation pathway designed to expand and deepen TOPMed multi-omics assets for HLBS research. The program is trying to catalyze a shift from association-driven genetics toward mechanistic, functionally grounded biology that can ultimately support personalized and precision approaches to prevention, diagnosis, and treatment. The expectation is that applicants will contribute high-quality, well-integrated omics and phenotype data that can be securely shared via NIH-controlled-access platforms, enabling broad reuse, replication, and method development across the scientific community.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01 - Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.233, 93.837, 93.838, 93.839, 93.840.
• This funding opportunity was created on 2025-09-22.
• Applicants must submit their applications by 2028-05-08.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 447

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