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This is a Request for Application (RFA) announcing a Notice of Funding Opportunity (NOFO) for computational modeling and analysis centers within the Impact of Genomic Variation on Function (IGVF) Consortium. The National Human Genome Research Institute (NHGRI) is soliciting applications under the UM1 activity code (Research Project with Complex Structure Cooperative Agreement) to develop, apply, and test predictive models and perform integrative analyses determining how genomic variation impacts genome function and phenotype. The NOFO was posted October 9, 2026, with an open submission date of November 14, 2026, and all applications are due by 5:00 PM local time by December 15, 2026. The earliest start date for funded projects is July 2027, with scientific merit review scheduled for August 2027 and advisory council review in September 2027. The funding opportunity number is RFA-HG-27-010, and the assistance listing number is 93.172 (Human Genome Research). Clinical trials are not permitted under this announcement.

Applicants must develop models predicting the impact of untested genomic variants on genome function and phenotype, share predictions through the IGVF catalog and data portal, guide experimental design optimization, provide analytical expertise for consortium-wide integrative analyses, and collaborate with other consortia on data integration and joint analyses. Centers must work collaboratively within the IGVF Consortium framework, contribute all data and methodologies to the IGVF Data and Coordinating Center, participate in working groups and steering committee meetings, and ensure consortium resources are accessible to diverse users. Research is limited to mammalian systems with preference for human studies using samples from genetically diverse populations. Eligible applicants include higher education institutions, state and county governments, tribal governments and organizations, 501(c)(3) nonprofits, for-profit organizations, small businesses, and other entity types, including non-domestic entities. Foreign subawards and subcontracts are not permitted under this NOFO. Applications must follow the Research Instructions in the How to Apply - Application Guide and may be submitted through NIH ASSIST, institutional system-to-system solutions, or Grants.gov Workspace.

RFA-HG-27-010-Full-Announcement.html

Text of this file

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

Computational Modeling and Analysis of the Impact of Genomic Variation on Function (UM1, Clinical Trial Not Allowed)

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-HG-27-010

Companion Funding Opportunity

RFA-HG-27-007

, UM1

Research Project with Complex Structure Cooperative Agreement

RFA-HG-27-008

, U24 Resource-Related Research Project (Cooperative Agreements)

RFA-HG-27-009

, UM1

Research Project with Complex Structure Cooperative Agreement

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.172

Funding Opportunity Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications to develop, apply, and test predictive models and perform integrative analyses to determine the impact of genomic variation on genome function. Centers funded through this initiative will become a part of the Impact of Genomic Variation on Function (IGVF) Consortium. As consortium members, centers will work together to ensure all consortium resources are accessible to a wide variety of potential users. Centers also will collaborate with other consortium components to guide and optimize IGVF experimental design, to provide analytical expertise and support for consortium-wide efforts, and to develop and execute shared analysis strategies to meet consortium goals.

Funding Opportunity Goal(s)

As a leading authority in the field of genomics, the mission of the National Human Genome Research Institute (NHGRI) is to accelerate scientific and medical breakthroughs that improve human health by driving cutting-edge research, developing new technologies, and studying the impact of genomics on society. Congress initially established NHGRI to characterize the structure and function of the human genome, including the mapping and sequencing of individual genes. This also includes reviewing and funding research proposals, developing training programs, coordinating international genome research, communicating advances in genome science to the public, and reviewing and funding proposals to address the ethical and legal issues associated with this research. NHGRI supports the development of methods, resources and technologies to improve the health of all humans through advances in genomics research. NHGRI supports research that accelerates foundational resources, technology development, and experimental and computational approaches for basic genomics and functional genomics research; for the application of genomics to medical science and clinical care; and to support ethical, legal and social implications (ELSI) research concerning societal issues that need to be addressed, especially as genomic science advances. For years, NHGRI has participated in the NIH effort to turn discovery into health by helping small businesses develop innovative genomics technologies that improve health and save lives. NHGRI also develops and supports initiatives that expand opportunities for genomics education and careers, cultivating genomics training programs and workforce development initiatives.

Key Dates

Posted Date

October 09, 2026

Open Date (Earliest Submission Date)

November 14, 2026

Application Due Dates
Review and Award Cycles
New
Renewal / Resubmission / Revision (as allowed)
AIDS - New/Renewal/Resubmission/Revision, as allowed
Scientific Merit Review
Advisory Council Review
Earliest Start Date

December 14, 2026

Not Applicable

Not Applicable

July 2027
August 2027

September 2027

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Expiration Date

December 15, 2026

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
Use the NIH ASSIST system to prepare, submit and track your application online.
Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background A major challenge in genomics is defining the role of genomic variation in influencing phenotypes in human biology and diseases. As outlined in NHGRI's 2020 Strategic Vision, studies characterizing the functional consequences of variants have not kept pace with studies of variant discovery or association, and this lack of functional genomic information remains a barrier that impedes progress in genomics.

The Impact of Genomic Variation on Function Consortium (IGVF) was established in 2021 to address the challenge of understanding how genomic variation affects genome function to influence phenotypes using a coordinated team-science approach. The program utilizes emerging experimental and computational genomic approaches to build a catalog of the impact of genomic variants on genome function and phenotypes and to share data and other resources with the scientific community.

Program Goals and Notices of Funding Opportunity (NOFOs) NHGRI is issuing an open call for applications to participate in a second phase of IGVF, based on recent community recommendations on functional variant interpretation and input from the National Advisory Council for Human Genome Research. The goals of the second phase of IGVF are to:

Test the impact of individual genomic variants on function
Study the effects of genomic variant interactions on function
Model and predict the impacts of genomic variation on function and phenotype
Expand a set of resources to enable future studies

To achieve these goals the following NOFOs are issued:

Systematic Characterization of Genomic Variation to Assess Effects of Individual Variants on Genome Function and Phenotype – RFA-HG-27-007
Genomic Variant Interactions With Other Variants Or The Environment – RFA-HG-27-009
Computational Modeling and Analysis of the Impact of Genomic Variation on Function – RFA-HG-27-010
IGVF Data and Coordinating Center – RFA-HG-27-008

NHGRI encourages all investigators with ideas aligned with the goals of this NOFO to submit applications.

Research Scope and Objectives For This NOFO Methods to accurately predict the impact of untested genomic variants on genome function and phenotype are needed because it is not feasible to experimentally test all genomic variants of interest in all contexts. IGVF modeling and analysis centers will develop models and perform integrative analyses predicting the impact of genomic variation on genome function, and share predictions with the research community through the IGVF catalog and data portal.

Objectives for IGVF modeling and analysis centers are:

Develop, apply, and test models predicting the impact of genomic variation on function and phenotype
Share predictions with the research community through the IGVF catalog and data portal
Guide and optimize IGVF experimental design
Provide analytical expertise, leadership, and support for consortium-wide integrative analyses
Work with other consortia and international groups to facilitate data integration and joint analyses

Key attributes of each objective are outlined below.

Develop, apply, and test models predicting the impact of genomic variation on genome function and phenotype Modeling and analysis centers will develop and/or refine computational models predicting at least one of:

Impacts of untested genomic variants (defined as changes in DNA, RNA, or protein sequence, impacting protein coding or non-coding regions of the genome, single variants or multiple variants simultaneously) on genome function and molecular, cellular, or organismal phenotype
The functional impacts of genomic variants in specific cell and spatial contexts
Interactions between genomic variants or between genomic variants and environmental factors
Systems or network-level effects of variants
Causal variants among the many variants associated with a disease or phenotype
The most informative subset of variants to test experimentally to optimize experimental design

Modeling and analysis centers will predict impacts of variation in human or mouse genomes.

Modeling and analysis centers will develop models that leverage existing and newly generated IGVF data and may utilize other data, and that generate hypotheses that can be tested experimentally. Centers will pursue modeling approaches that are generalizable to systems beyond those they are studying and should demonstrate flexibility to accommodate new and emerging data.

Modeling and analysis centers will pursue interpretable models that allow for a clear understanding of contributions of model parameters and model biases and that enable a greater understanding of biological mechanisms, and that leverage biochemical, biophysical, and other mechanistic information.

Modeling and analysis centers will work collaboratively to evaluate models through rigorous validation, benchmarking, comparisons with existing approaches, or other evaluations to assess the accuracy, quality, or utility of the developed approaches.

Modeling and analysis centers will share models, model parameters, predictions, and software in robust and reproducible open-source formats enabling community reuse and model modification and interpretation, and share thorough documentation, tutorials, educational materials, and other guidance for model implementation as appropriate.

Share predictions with the research community through the IGVF catalog and data portal Modeling and analysis centers will share predictions from models and integrative analyses with the research community through the IGVF catalog and data portal. Centers will work collaboratively with other IGVF components to share predictions in formats that are readily searchable, interpretable, and useful for the research community in hypothesis generation or prioritization of downstream experimental testing and validation.

Guide and optimize IGVF experimental design Modeling and analysis centers will lead and work collaboratively with other IGVF components to optimize experimental design and data collection strategies to maximize the consortium's overall impact, including but not limited to:

Guiding consortium efforts in adaptive experimental design, including iterative cycles of data collection, modeling, and model testing with targeted experiments
Leveraging models and conducting analyses to prioritize genomic regions or variants for experimental testing
Identifying benchmarking and ground truth data sets
Identifying experimental and analytical design parameters

Provide analytical expertise, leadership, and support for consortium-wide integrative analyses Modeling and analysis centers will coordinate and perform integrative analyses, including analyses across projects from all four IGVF components, and lead and coordinate consortium efforts to develop standards for data, metadata, analyses, and predictions that will enable their sharing and re-use. These activities may occur in part through leadership of and participation in an IGVF Integrated Analysis Working Group.

Work with other consortia and international groups to facilitate data integration and joint analyses:

IGVF will continue to collaborate with other projects with shared interests in variant interpretation. Modeling and analysis centers will coordinate and contribute to consortium efforts to work with groups beyond IGVF to perform joint analyses and to converge on shared standards for data, metadata, analyses, and predictions that will enable broad sharing and re-use.

Consortium Formation and Coordination.

This NOFO uses the cooperative agreement award instrument. Modeling and analysis centers will become members of the IGVF Consortium. Consortium members are expected to work collaboratively with NHGRI and the larger consortium towards meeting consortium goals, in addition to the specific research goals outlined in their individual applications.

Members of the IGVF Consortium will work together to:

Develop a catalog of the impact of genomic variants on genome function and phenotypes.
Plan experiments, implement studies, and analyze results from within component and consortium-wide projects, typically through working groups.
Develop agreed-upon standards and metrics for data, metadata, data quality, and analysis.
Contribute all data, metadata, protocols, methodologies, analyses, software, and other products to the IGVF Data and Coordinating Center (DACC) in specified formats.
Share best practices and lessons learned within the consortium and with the external community.
Lead and actively participate in consortium-wide, Steering Committee, and working group meetings.
Contribute to training across the consortium, cross-consortia efforts, and broader outreach efforts.

Consortium members are expected to coordinate assays, variants, and cell types and to develop shared analysis strategies and uniform computational workflows, when applicable, to meet consortium goals, rather than function as independent projects with independent goals. When appropriate, selection of variants and cell types in this second program phase should be done in consideration of variants and cell types characterized in the first phase of IGVF (https://data.igvf.org/resources/). IGVF research is limited to mammalian systems, with a preference for human studies including samples derived from individuals across a breadth of genetic ancestries. Variants selected for testing should account for allele frequencies and disease associations within and across human populations. Proposed cell types and states should be derived from tissues important in development, differentiation, or human diseases.

A central goal of IGVF is the development of data, tools, and other resources that can be used by researchers not funded by this program. Consortium members will be expected to generate pipelines, tools, and educational materials that facilitate community uptake of IGVF data and methods, and to work together to ensure all consortium resources are accessible to a wide variety of potential users. Data, predictions, and models should be shared early and organized in ways that enable a variety of uses by the broader scientific community, from searches of individual variant impacts to large scale integrative or machine learning approaches.

Consortium members will also be expected to continue to collaborate with other projects and consortia with interests in variant interpretation and coordination across resources, especially in efforts to develop shared data processing and analysis pipelines to enable data sharing and comparisons. This includes work with the Atlas of Variant Effects (AVE) Alliance, The Molecular Phenotypes of Null Alleles in Cells (MorPhiC), the Clinical Genome (ClinGen) Resource, the Genomics Research to Elucidate the Genetics of Rare Diseases: Innovation (GREGoRi), the Human Pangenome Reference Consortium (HPRC), and other NHGRI-led consortia, as relevant.

Consents and Data Sharing in IGVF A key deliverable of IGVF is the development of two public data resouces, the IGVF Catalog and Data Portal. To facilitate user access to these resources,NHGRI expects that centers will prioritize the use of samples derived from research participants that have been consented for the broadest possible sharing of genomic data, such as consent for unrestricted access, or for general research use and broad sharing through controlled access. Consent language should also avoid restrictions on the types of users who may access this data for genomics research.

To Learn More An informational webinar will be held where NIH staff will present overviews of IGVF NOFOs and answer NOFO-related questions from prospective applicants. Time, date, and webinar links will be made available through a Notice in the NIH Guide.

The webinar is open to all prospective applicants, but participation is not required to apply.

Prospective applicants are strongly encouraged to contact NHGRI Staff listed as Scientific/Research Contact(s) below to discuss the responsiveness and alignment of their proposed work with program goals.

Applications Not Responsive to this NOFO The following types of applications are not responsive to this NOFO and will not be reviewed:

Applications that propose extensive wet-lab data generation. Applicants may propose limited (<10% annual direct costs) wet-lab work to inform modeling efforts.
Applications that propose developing predictive models that are not comprehensive in scope (e.g., applicable to only one or a small set of genomic loci/sequences/elements).
Applications that propose developing predictive models that are not generalizable (e.g., applicable to one or a small number of

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NHGRI intends to commit up to $5,000,000 in FY2027 to fund up to five awards.

Award Budget

Application budgets are limited to $800,000 direct costs and need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions - Includes all types
Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

Small Businesses
For-Profit Organizations (Other than Small Businesses)

Local Governments

State Governments
County Governments
City or Township Governments
Special District Governments
Indian/Native American Tribal Governments (Federally Recognized)
Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

Independent School Districts

Public Housing Authorities/Indian Housing Authorities

Native American Tribal Organizations (other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy section is limited to 30 pages, exclusive of the Specific Aims page.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

SF424(R&R) Other Project Information

SF424(R&R) Senior/Key Person Profile

R&R Budget

For single PD/PI applications, the PD/PI is expected to devote at least 3 person months, based on a 12-month calendar. If multi-PDs/PIs are proposed, then each PD/PI is expected to commit sufficient time to serve his/her proposed role, with a minimum aggregate PD/PI effort of 3 person months and at least one PI devoting 2 months. The appropriateness of the effort of key personnel must be justified in the budget justification.
Budgets should include support for a dedicated Project Manager who will devote a minimum of 4 person months, based on a12-month calendar, to oversee the day-to-day activities of the center, coordinate metadata and data submissions to the DACC, coordinate center participation in integrative analyses, coordinate across center sites, if applicable, and be responsible for promptly providing requested reporting information to NHGRI Program Staff. A PD/PI may serve as the Project Manager.
Budgets should include funds for the PD(s)/PI(s) and key personnel to attend the initial consortium kickoff meeting, and for the PD(s)/PI(s) and 2–6 members of the center to attend annual consortium meetings thereafter that start in year 1.
For each year of the award, years 1-5, 20% of the direct costs must be allocated to support collaborative work in consultation with and with approval by NHGRI staff. This work is anticipated to further both the needs of the funded centers, the IGVF Consortium, and the genomics research community.
Budgets should include any funds required to support sharing of scientific data under this NOFO. This should include funds to prepare data for submission to the IGVF DACC and the IGVF data portal. NIH provides guidance on allowable costs for data management and sharing here. For projects generating genomic data derived from research participants, investigators should consider costs associated with complying with the NIH and NHGRI GDS Policy expectations (e.g., obtaining samples with explicit informed consent for future research use and broad data sharing, implementing processes to seek new consent from study participants, etc.).

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Applicants should address Sections 1-4 below. It is expected that sections 2 and 3 constitute the bulk of the proposal.

Section 1. Overview Applicants should provide an overview of the proposed modeling and analysis center, describe its significance and innovation, and succinctly address how it proposes to achieve the major objectives of this NOFO.

Section 2. Research Proposal Applicants should describe their proposed approaches to develop, apply, and test models predicting the impact of genomic variation on genome function and phenotype and to share predictions through the IGVF catalog.

Develop, apply, and test models predicting the impact of genomic variation on genome function and phenotype Applicants should describe in detail their plans to develop and/or refine computational models predicting at least one of:

Impacts of untested genomic variants (defined as changes in DNA or RNA sequence, protein coding or non-coding, single variants or multiple variants simultaneously) on genome function and molecular, cellular, or organismal phenotype
The functional impacts of genomic variants in specific cell and spatial contexts
Interactions of genomic variants or of genomic variants and environmental factors
Systems or network-level effects of variants
Causal variants among the many variants associated with a disease or phenotype
The most informative subset of variants to test experimentally to optimize experimental design

Applicants should address aspects of model development that include but are not limited to:

Plans for leveraging existing and newly generated IGVF data to develop and test models
Generalizability of models and approaches to systems beyond those they are studying. Given the importance of understanding all variation in the human genome, applicants should describe how approaches will be applicable to a breadth of genetic ancestries and allow for consideration of sex as a biological variable.
Flexibility to accommodate new and emerging data
Interpretability of models and potential biases
Use of biological, biochemical, biophysical, and other mechanistic information

Applicants should detail plans to evaluate models through validation, benchmarking, comparisons with existing approaches, or other evaluations to assess the accuracy, quality, or utility of the developed approaches.

Wherever possible, applicants should indicate plans to adopt and use community-standard formats, vocabularies, ontologies, and quality metrics.

Share predictions with the research community through the IGVF catalog Applicants should describe plans to share predictions from models and integrative analyses with the research community through the IGVF catalog, and describe how predictions will be shared so they are searchable, interpretable, and useful for hypothesis generation or prioritization of downstream experimental testing and validation.

Section 3. Collaborative Proposal Applicants should describe their proposed approaches to lead and participate in collaborative IGVF activities including guiding and optimizing IGVF experimental design, providing analytical expertise and support for consortium-wide efforts, and working with other consortia and international groups.

Guide and optimize IGVF experimental design Applicants should describe their plans to lead and work collaboratively with other IGVF components to optimize experimental design and data collection strategies to maximize the consortium's overall impact, potentially including:

Plans for iterative data collection, modeling, and model testing with targeted experiments
Plans to leverage models and analyses to prioritize genomic regions or variants for experimental testing
Plans to develop or identify benchmarking and ground truth data sets and experimental and analytical design parameters so IGVF data, predictions, and models will be useful as community resources beyond the IGVF consortium

Provide analytical expertise and support for consortium-wide efforts Applicants should describe plans to lead, coordinate, facilitate, and perform integrative analyses, including analyses across projects from all IGVF components. Planned contributions and effort levels of specific personnel towards these activities should be detailed, along with descriptions of relevant prior experience.

Work with other consortia and international groups to facilitate data integration and joint analyses:

Applicants should indicate willingness to work collaboratively with groups beyond IGVF to perform joint analyses and to converge on shared standards for data, metadata, analyses, and predictions, and may propose specific plans to collaborate with groups beyond IGVF including how the proposed collaborations may help achieve IGVF objectives.

Section 4. Management Plan Applicants should describe the organization of the proposed center and its management structure, including decision-making processes. Personnel responsible for key tasks, such as model development, collaborative activities including leading consortium-wide integrative analyses and experimental design, as well as the project manager responsible for managing day-to-day operations, should be identified. Applicants should succinctly describe relevant previous experience (without duplicating information contained in the biosketches) and how their expertise aligns with key objectives of the NOFO.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

The following instructions also apply:

The Resource Sharing Plan should summarize whether and how resources (e.g., educational materials; methods; models; physical products, materials, and reagents; protocols; research findings and products; and software) will be made available. Applicants should include a description of the format, an indication of who will be responsible for implementation and plans for long-term maintenance, whether there will be opportunities for community input and feedback, platform(s) or mechanism(s) that will be used to make resources publicly accessible, and proposed timeline for implementing the Resource Sharing Plan. Resource Sharing Plans should not duplicate other sections of the main Research Plan but should refer to them when appropriate. After initial review, NHGRI program staff may negotiate revisions of this plan with the prospective recipient. The final negotiated version of this plan will become a term and condition of the award.

In addition to the above expectations, NHGRI expects that plans for sharing software generated under this funding opportunity will meet the following expectations:

Applicants should detail plans to enable community reuse, extension, modification, and interpretation of models, including plans to share models, parameters, predictions, and software in robust and reproducible open-source formats through version-controlled public repositories, and share documentation, tutorials, educational materials, and other guidance for model implementation as appropriate.
Applicants sharing software are encouraged to consider the NIH Best Practices for Sharing Research Software and the Findable, Accessible, Interoperable, Reusable for Research Software (FAIR4RS) Principles and to use software licenses that allow for unrestricted redistribution and modification of the software.
Source code should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories. The terms of software availability should permit the commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
NHGRI encourages making software citable with persistent identifiers such as a DOI or a citation.cff.
To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
Software should be containerized and promote reproducibility and use of automated pipelines, where possible. Developed software are expected to be tested utilizing a relevant testing framework, as appropriate (e.g., unittest).
Applicants should take responsibility for creating the original and subsequent "official" versions of a piece of software.

For more guidance on writing a Resource Sharing Plan, see https://www.genome.gov/about-nhgri/Policies-Guidance/Writing-a-Resource-Sharing-Plan.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.
Recipients must comply with the NIH Genomic Data Sharing Policy (NIHGPS 8.2.3.3).
All scientific data, metadata, and predictions should be submitted to the IGVF Data Portal. The IGVF DACC will be responsible for additional deposition into appropriate NIH-designated repositories.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

Foreign Organizations Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372) This initiative is not subject to intergovernmental review.

6. Funding Restrictions All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Mandatory Disclosure

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.36.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this NOFO:
Evaluate the likelihood that the proposed project will generate predictions and analyses that will be of high utility to the research community and contribute to consortium goals.
Evaluate the extent to which the proposed collaborative plans are likely to enhance collaboration and teamwork within the consortium and lead to improved consortium-wide outcomes.
Evaluate the likelihood that the proposed strategies will enable the study of the impact of genomic variation on genome function and phenotypes relevant to human health and disease.

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this NOFO:
Assess whether the application describes sufficient leadership involvement for day-to-day project management activities (e.g., a project manager and sufficient PD(s)/PI(s) effort).
Assess whether the application describes sufficient effort for collaborative activities (including leading integrative analyses, guiding experimental design, and providing analytical expertise to the consortium).
Assess the project team's track record of broadly disseminating models, tools, and software.

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?

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