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

FAQs: NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (PAR-25-447)

What is PAR-25-447?

PAR-25-447 is an NIH Notice of Funding Opportunity (NOFO) from the National Heart, Lung, and Blood Institute (NHLBI) focused on the TOPMed program. It invites projects that generate and integrate large-scale genetic and multi-omics datasets to clarify biological mechanisms behind heart, lung, blood, and sleep (HLBS) disorders.

What is the main purpose of this opportunity?

The purpose is to move from genetic association findings toward mechanistic understanding. Projects are expected to create omics-based phenotypes and integrated datasets that connect genetic variation to molecular and cellular function, rather than stopping at statistical links between variants and traits.

What does TOPMed refer to in this NOFO?

TOPMed stands for Trans-Omics for Precision Medicine, an NHLBI-funded program designed to support creation of high-volume omics datasets and related resources that can be used broadly by the research community.

What activity code does this NOFO use, and why does it matter?

This NOFO uses the X01 activity code. Under X01 awards, no grant funding is provided to the applicant. Instead, the mechanism is commonly used to provide access to a resource, infrastructure, or coordinated program support. In this case, the core resource is TOPMed-enabled data generation and integration efforts.

Does an X01 award provide any direct dollars to support the research?

No. The defining feature described for this opportunity is that it provides no grant funding under the award. The value of the award is participation in, or access to, TOPMed resources and coordinated support for data generation and integration, with the goal of producing shared community datasets.

Is this opportunity focused on research use and data generation, or on delivering a clinical service?

It is explicitly focused on research use and data generation. The emphasis is on producing and integrating large-scale omics datasets and phenotypes that can be used by the broader community to accelerate discovery in HLBS disorders.

Are clinical trials allowed under this NOFO?

No. The NOFO is labeled "Clinical Trial Not Allowed," which means applications should not propose prospective interventional clinical trials as part of the work.

What kinds of diseases or conditions are in scope?

The scope includes heart, lung, blood, and sleep (HLBS) disorders. The work is aimed at clarifying the biological mechanisms behind these disorder areas using genetic and multi-omics approaches.

What does the NOFO mean by moving from "genetic map" to "mechanism"?

It means the program is looking for studies that explain how genetic factors drive disease biology. Examples of the kinds of mechanistic targets described include genes, regulatory elements, pathways, cell types, molecular networks, and biological processes that link genotype to phenotype.

What types of data are expected to be generated or integrated?

The NOFO centers on large-scale genetic and multi-omics datasets and omics-based phenotypes. It highlights combining multiple layers of biology, such as genome sequence with transcriptomics, epigenomics, proteomics, metabolomics, and other omics measurements, then interpreting them together in an integrated way.

Is the opportunity interested in AI or machine learning methods?

Yes. The NOFO signals interest in the use of AI and machine learning where appropriate, especially for integrating complex multi-modal datasets, discovering patterns, prioritizing mechanisms, and improving interpretability and predictive power of mechanistic models.

What are the data sharing expectations?

Genomic data and associated phenotype information generated under this NOFO are expected to be deposited into NIH-designated controlled-access repositories. The stated examples include dbGaP and NHLBI BioData Catalyst (BDC). The intent is to make resulting datasets shared community assets while protecting participant privacy.

Why does the NOFO require controlled-access repositories?

Because human genomic and health-related phenotype data can be sensitive. Controlled-access systems manage access through formal processes to protect participant privacy while still enabling broad scientific use.

Which repositories are specifically mentioned for data deposition?

The NOFO specifically mentions the NIH database of Genotypes and Phenotypes (dbGaP) and NHLBI BioData Catalyst (BDC) as examples of controlled-access platforms where data are expected to be deposited.

Who is eligible to apply?

Eligibility is broad and includes many U.S. organizations and government 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.

Are non-U.S. (non-domestic) entities eligible?

Yes. The eligibility list explicitly includes non-domestic (non-U.S.) entities among eligible applicant categories.

Are tribal entities eligible to apply?

Yes. The NOFO lists federally recognized tribal governments and also tribal organizations that are not federally recognized as eligible applicants.

Does the NOFO encourage applications from institutions serving underrepresented groups?

It highlights additional eligible applicant categories including Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISI), among others.

Are faith-based or community-based organizations eligible?

Yes. The NOFO includes faith-based or community-based organizations in the additional eligible applicant categories.

Are small businesses and for-profit organizations eligible?

Yes. The NOFO lists small businesses and also for-profit organizations other than small businesses as eligible applicants.

What federal program areas or identifiers are associated with this NOFO?

The NOFO is associated with multiple CFDA numbers: 93.233, 93.837, 93.838, 93.839, and 93.840. These reflect NHLBI and related NIH program areas connected to heart, lung, and blood research.

What is the funding instrument type and administrative category?

Administratively, the opportunity uses the grant funding instrument type and is categorized as discretionary. However, the practical detail emphasized in the description is that the X01 mechanism does not provide grant funds to the applicant.

When is the closing date for PAR-25-447?

The original closing date listed is May 8, 2028, suggesting a long application window and the likelihood of ongoing submission cycles or continued participation as TOPMed evolves.

What is the expected outcome for the broader community?

The expectation is that projects will contribute high-quality, well-integrated omics and phenotype data that become securely shared community assets via NIH-controlled-access platforms, enabling broad reuse, replication, and method development across the scientific community.

What is the overall best way to interpret this opportunity?

It is best understood as an access-to-resource and data-generation pathway tied to TOPMed, designed to expand and deepen multi-omics assets for HLBS research and to accelerate a shift from association-driven genetics to functionally grounded, mechanistic biology.