Part 1. Overview Information

Key Dates

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).

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.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. 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.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

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

There is a continued need for systematic efforts to characterize the impact of individual variants on genome function and phenotype. In the first phase of IGVF, multidisciplinary teams worked together as functional characterization centers to start variant assessments across variant types, non-coding and protein-coding regions, cell types, tissues, and diseases. They planned to characterize more than two million genomic perturbations (i.e., variants, elements, and genes) across biological systems including hematopoietic and immune, cardiometabolic, and neuronal utilizing a variety of assays. Most importantly, they worked together to develop a collaborative framework for generating and analyzing data, and the building of a community resource.

It is currently not possible to experimentally test every variant. However, it is imperative to explore the extent to which we can effectively characterize variants and learn about their impact on function. In this second phase, NHGRI seeks to support centers to continue studies focused on perturbing variants and elements to test and characterize the roles of individual variants on genome function. In this phase, centers will work towards increasing testing throughput and will maximize the variant space covered to enable others to utilize these data and analyses.

The objectives of these centers are to:

• Select genomic variants and/or elements for systematic testing in these studies.
• Apply genomic perturbation methods and assay the impact on biologically relevant phenotypes.
• Develop robust, reproducible, and portable data processing pipelines.

The scope of this NOFO also includes the following:

• Contribute to expansion of the IGVF catalog for the community.
• Generate multi-omic reference maps of gene and regulatory element activity at single-cell resolution (optional).
• Improve generalizable approaches for high-throughput functional characterization assays (optional).

Select genomic variants and/or elements for systematic testing in these studies. Characterization centers will testnon-coding (DNA, RNA) variants, protein-coding variants and/or elements, using individual and/or multiplexed assays, in one or more cell types and states that are of high value to the research community. These centers are encouraged to foucs on variants or elements associated with disease, or those likely to provide new insights into variat function. Examples of variants that could be tested include, but are not limited to, human variants associated with common disease (e.g., Genome-Wide Association Studies (GWAS)), rare disease (e.g., Mendelian), clinically annotated variants (e.g., Clinical Genome Resource (ClinGen)), uncharacterized variants (e.g., from resources such as the ClinVar database, and the Genome Aggregation Database (gnomAD)), or variants not yet observed in humans. Systematic focus on variants associated with disease areas are encouraged and the likelihood to provide new insights into variant function should be well justified. Examples of elements include those that harbor candidate disease association variants or candidate regulatory elements for disease-associated genes. Applicants should propose study of one or more cell types and states that are of high value to the research community.

Characterization centers must balance systematic sampling of variants and/or elements with the testing capacity of the proposed assays. A continued goal of IGVF is to maximize the utility of the generated data and analyses by balancing the breadth and depth of biology that are sampled by IGVF to cover as many areas as possible. To meet this goal, Characterization centers should be flexible enough to accommodate work on cell types and variants that may differ from what was specifically proposed in their application.    

Apply genomic perturbation methods and assay the impact on biologically relevant phenotypes. Characterization centers must balance will apply up to three existing, state-of-the-art high-throughput genomic perturbation methods. Examples include, but are not limited to, massively parallel reporter assays, genome editing, epigenome editing and high-throughput protein mutagenesis. Characterization centers will use biological systems relevant to human health and disease that include, but are not limited to, primary cells, organoids, intact animals, cell lines, and cell-free assays. Applicants may propose to detect phenotypic changes at one or more scales, such as molecular (e.g., RNA abundance or kinase activity), cellular (e.g., morphology), multi-cellular (phenotypes that require interaction of more than one cell type, which need not be cell autonomous phenotypes), or organismal phenotypes (e.g., behavior or development).

Develop robust, reproducible, and portable data processing pipelines. Characterization centers will develop or adopt data processing pipelines consistent with their proposed assays. These may include standardized pipelines currently in use by IGVF. If pipeline development is proposed, the proposed pipeline should be at a state of development at the start of year 1 where the primary focus is to complete development and move towards production (hardening). Each center is expected to specify data processing pipelines appropriate for their assays that are containerized, robust, reproducible, and portable. The IGVF Data and Coordinating Center (DACC) will work with the consortium to harden pipelines. Pipeline development and hardening are expected to be completed by the end of year 1. In some cases, a center may be responsible for running these pipelines themselves, or they may work with the DACC on data processing. The consortium will make decisions about data processing pipelines and implementation responsibilities early during the first year of phase 2.

Contribute to expansion of the IGVF catalog for the community. A primary goal of the IGVF Consortium is to collaboratively produce a set of resources centered on a searchable catalog of measured and predicted variant impacts. For all variants and elements tested by the consortium, the catalog will enable the search for information about variants and elements such as perturbations, phenotypic assays, biological systems, assay results, interpretations, and predictions. The DACC will lead on the development of the catalog in collaboration with other IGVF components. Characterization centers will be expected to provide feedback to the DACC about representations of their data and analyses and specify use cases that should be supported by the catalog.   

Generate multi-omic reference maps of gene and regulatory element activity at single-cell resolution (optional). In phase 1 of IGVF, shared reference maps of single cell and gene regulatory element activity were collected across all characterization samples to enable integrative analyses and further insight into measured and predicted variant and gene function. Characterization centers may use propose a portion of their resources for limited generation of multiome profiling data (not to exceed 10% of budget) for samples proposed for study in their centers that were not previously mapped in IGVF phase 1 or in other studies. Mapped assays should include collection of single cell transcription and chromatin accessibility data (single cell RNA sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq)). Paired multiome methods that enable assaying of transcription and accessibility in the same cell are highly encouraged. Data should be collected at high depth to be consistent with data collection in phase 1 (>5,000 cells per cell state, >5,000 ATAC unique molecular identifiers per cell).

Improve generalizable approaches for high-throughput functional characterization assays (optional). Characterization centers will collect data collection based on genomic methods that are robust and ready to be utilized at the time of funding. However, Characterization centers  may propose to use a small portion of their resources (not to exceed 10% of budget) to develop or refine experimental and computational approaches for functional characterization. Such improvements should directly aid experimental data generation. Technology development under this NOFO is limited to approaches for functional characterization that are high-throughput, generalizable across experimental systems and diseases, with the potential to be implemented during the current project period.

 Consortium Formation and Coordination 

This NOFO uses the cooperative agreement award instrument. Characterization 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.

Recipient responsibilities will include:

• 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 analyses.
• 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 participating 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. IGVF research is limited to mammalian systems, with a preference for human studies including samples derived from individuals across a breadth of genetic ancestries and the consideration of sex as a biological variable. 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 resources, 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 these 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 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 the email address listed as the 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 are primarily developing new experimental methods.
• Applications that do not use biological systems relevant to human health and disease.
• Applications that focus on mechanistic studies or a single disease.
• Applications that do not indicate plans to collaborate with and contribute to consortium-wide, collaborative activities and analyses throughout the course of the project.

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

Section II. Award Information

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

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.

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.

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 is limited to 30 pages (exclusive of the Specific Aims page).

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

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

The PD(s)/PI(s) must designate a dedicated Project Manager to direct the day-to-day operations of the Coordinating Center. A PD/PI may serve as the Project Manager.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

• 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 a 12-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

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

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

Specific Aims: Describe the specific goals of the Individual Variant Characterization Center and its role in achieving the overall objectives of the IGVF Consortium.

Research Strategy: In the Research Strategy, applicants should propose plans, approaches, and potential alternative strategies for carrying out the goals of the Individual Variant Characterization Center. The Research Strategy should consist of the following sections uploaded as a single PDF attachment:

1. Center Overview
2. Approach–Genomic Variant/Element Selection and Experimental Assays
3. Approach–Data Processing and Data Management
4. Approach–Reference Mapping and/or Assay Improvements (Optional)
5. Center Management

Details about what should be discussed in each section are described below.

Center Overview

• Provide an overview of the proposed Individual Variant Characterization Center and the goals of the center. This section should address the significance, innovation, and approach of the proposed center and center's plans. These should be further detailed in the later sections. The first two may be included here under subsections titled, "Significance" and "Innovation". All three should be further detailed in the later sections.
• Provide a description of the readiness of assays to achieve the goals of the center at scale and significance of the proposed studies to human health and disease.
• Provide an overview of the study's innovations and explain plans to balance using state-of-the art methods and analyses with the ability to deliver useful data and analyses to the community.
• Provide an overview of the approach and the rationale used to propose choice of methods, variants, biological systems, analyses, and expected outcomes. To note, these centers are generating a resource of data and analyses intended to be used to enable discovery science and generate hypotheses as opposed to being hypothesis driven projects.

Approach–Genomic Variant/Element Selection and Experimental Assays

• Describe the plan and rationale for the selection of genomic variants and/or elements for systematic testing. This should include the selected balance of non-coding (DNA, RNA) or protein coding variants and/or elements and why the proposed approach has high potential to provide novel data to the IGVF catalog. This should also include an explanation for the balance of disease variants (common and/or rare), uncharacterized variants, and variants not yet observed in humans.
• If proposed, plans focused on disease variants should include a rationale for the focus on the selected disease variants and how these studies will provide new insights into variant function. 
• If appropriate, explain the rationale for the selected balance of elements that harbor candidate disease association variants or candidate regulatory elements for disease-associated genes.
• Describe considerations for balancing a systematic sampling of variants and/or elements and testing capacity.
• Describe the high-throughput genomic perturbation methods (up to three existing) proposed for these studies, the rationale for the choice of assay(s) and choice of phenotype(s) in relation to the variants/elements proposed for study, the biological system(s) used, and the rationale for the biological system(s) used, including relevance to human health and disease. Proposed cell types and states should be derived from tissues important in development differentiation, or human diseases associated with known genomic variants. Where relevant, describe the process for acquiring appropriate consents for future use and broad genomic data sharing via unrestricted access and/or controlled-access.
• Address robustness of assays at time of application, including performance at the proposed experimental scale and resolution. These should be based on demonstrated capability and included in preliminary data. Provide a description of the extent of prior use, throughput, sensitivity, specificity, and success rate to support the rationale for use of the proposed assay(s).
• Describe the balance between the number of samples versus the number of assays per sample, and balancing throughput with biological relevance. In describing the proposed assays and samples, detail the approach or overall experimental strategies for implementing these studies and how results will be interpreted. This should include potential problems, alternative strategies, and benchmarks for success as well as how the proposed method(s) is innovative. This may include innovative application of the proposed assay(s) to testing of specific variants/elements within the specified cell types of biological systems.
• Descriptions of variants/elements and assays should address how approaches could generalize to applications beyond the selected variants, biological systems, and cell types. This should include a description of how generated data and analyses could be incorporated into the work of the broader consortium. This should also include a plan for contributing to the IGVF catalog of measures and predicted variant effects, and address providing feedback to the DACC about implementation and specifying use cases appropriate to the center's data types and analyses.

Approach–Data Processing and Data Management

• Describe plans for development or adoption of data processing pipelines appropriate for analysis of the raw data derived from the proposed assays. This should include plans to complete development and move towards pipeline production (hardening) completion by the end of the first year. This should also include a process for running/implementing these pipelines, which may occur in a recipient's laboratory, and working with the DACC for the submission of both metadata and data (raw and processed) in standardized formats, as well as the submission of information about assays, variants, samples, experimental approaches, and analysis methods. This should include plans for standardizing pipelines or working with the DACC on standardization, as needed. Plans may address expected requirements for pipelines such as cost per sample, and storage and computing intensity needs. Budgets should account for development and/or adoption of pipelines, and pipeline production.
• Describe plans for establishing an informatics infrastructure for tracking and managing metadata, data, quality control, and the submission of these to the DACC (e.g., a LIMS system) without duplicating information in the Resource Sharing Plan and Data Management and Sharing Plan attachments.
• Describe plans for sharing datasets, metadata, software, or other outcomes of the proposed studies in robust and reproducible formats  without duplicating information in the Resource Sharing Plan and Data Management and Sharing Plan attachments.
• For the above descriptions, be sure to describe any needed software development in detail.

Approach–Reference Mapping and/or Assay Improvements (Optional)

• As needed, describe plans for limited generation of single cell multiome profiling data. These should be for samples proposed for study in the center that have not previously been mapped in IGVF phase 1 or other studies. Single cell transcription and chromatin accessibility data should be collected at high depth to be consistent with data collection in phase 1 (>5,000 cells per cell state, >5,000 ATAC unique molecular identifiers per cell). Describe the genomic mapping assay(s) proposed, the rationale for the proposed assays, the expected data to be generated including scale, resolution, and how the results will be incorporated with other center data, including use of phase 1 data processing pipelines.
• Description above should include the proposed samples, number of each sample expected to be analyzed, and the rationale for the selection of these samples. Assays utilized should be well-established and perform at the proposed experimental scale and resolution. Resources dedicated to mapping should not exceed 10% of the proposed budget.
• As needed, describe plans for developing and/or refining experimental and/or computational approaches for functional characterization. Describe the expected improvement (i.e. throughput, sensitivity, specificity, other factors), generalizability of the technology across experimental systems and diseases, and the potential for other groups to adopt the technology.
• Descriptions should explain the potential to implement the technology during the current project period and how the technology might complement or replace other methods proposed for the center. Resources dedicated to these improvements should not exceed 10% of the proposed budget.

Center Management

• Describe how the center will be structured to achieve the center's goals. This should include the management structure of the center, overall center leadership, role of the Project Manager responsible for day-to-day operations, components of the center and how they will be integrated to form a cohesive center, key personnel, and their responsibilities (such as those responsible for data generation, data analyses, and data submission; each center will be expected to have a dedicated data submitter that will liaise with the DACC). This should include a description of the expertise of the team without duplicating information in biosketches, and a description of how consortium activities will be managed and management of any external collaborations, if relevant.
• Discuss experiences (if any) in working as part of interdisciplinary teams and/or large collaborative research efforts. To address collaborative potential, provide a vision/structure of how the center will work with other components on consortium-wide activities such as coordinating assays and variants, developing pipelines to be used by other centers, comparing across approaches, and working with others on shared analyses. This should outline examples and describe how the center will be set up to modify activities and respond to emerging consortium plans. Include descriptions of consents or material transfer agreements that allow for sharing of samples with other consortium-supported centers. Budgets should account for integrative analyses with data from other components of IGVF.
• In a subsection titled "Milestones," include a detailed timeline and milestones for tracking all aspects of the center and the proposed studies. These should include milestones for data generation expectations, data submissions, and plans for integrative analyses on a yearly basis. Milestones should also include points of interactions with other Individual Variant Characterization centers, other IGVF components, and the DACC. Whenever feasible, milestones should provide quantitative metrics for assessing the center's progress. As needed, milestones will be reviewed and updated in consultation and with the approval of NHGRI.

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 awardee. 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 sharing software are encouraged to consider the NIH Best Practices for Sharing Research Software and the Findable, Accessible, Interoperable, and 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 if the original investigators are 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 where 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

All instructions in the How to Apply - Application Guide must be followed.

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

All instructions in the How to Apply - Application Guide must be followed.

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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.

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).

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.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group(s) convened  by CSR, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned  to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Synergy with other IGVF funded projects and program balance, including a variety of experimental assays, throughput, and capacity of approaches.
• Potential to work effectively in interdisciplinary teams and/or large collaborative research efforts.
• Adequacy of data, software and analysis, and resource sharing plans as determined by NHGRI program staff.
• Whether the PD/PI will be funded through other IGVF NOFOs. NHGRI may choose to limit awards from multiple NOFOs to broaden research community participation in IGVF.
• Inclusion of new investigators and experienced investigators that are new to NHGRI consortia.
• Expansion of the community of genomics science to include new investigators and experienced investigators who are new to this field.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• Determining research approaches, designing protocols, setting project milestones and timelines, and conducting research.
• Ensuring that the software, resources, materials, etc. produced as part of this project are released appropriately according to the Resource Sharing Plan, IGVF Consortium policies, and NIH policies.
• Ensuring that the data produced as part of this project are released appropriately according to the Data Management and Sharing Plan, IGVF Consortium policies, and NIH policies.
• Preparing abstracts, presentations and publications in a timely manner.
• Adhering to policies regarding sharing of genomic and other types of data, data access, and standardized formats; timely publication; and intellectual property established by the NIH, NHGRI, and the Steering Committee (SC).
• Not disclosing confidential information.
• Interacting with other relevant NHGRI and NIH activities to promote synergy and consistency among similar or related projects.
• The PD/PI and his/her staff will be required to fully participate with NIH staff, External Scientific Consultants (upon NHGRI request), IGVF Consortium investigators, and one another. This includes collaborating with other projects and consortia, such as 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 (GREGoR), the Human Pangenome Reference Consortium (HPRC), and others, as relevant.
• Serve as a member of the IGVF Consortium Steering Committee (SC).
• Attending and participating in SC and other working group meetings and accepting and implementing decisions made by the SC
• Collaborating with the Data and Coordinating Center (DACC). Recipients that are part of a consortium will work collaboratively with a DACC that is tasked with a variety of roles, such as: ensuring that the products are the highest quality, developing standards; disseminating information; providing logistics, outreach and training, etc. In order for the collaboration to be effective, PDs/PIs are responsible for:
  • Ensuring that the Recipient receives the appropriate approvals for sharing data between the DACC and selected data repositories such as AnVIL, dbGaP, GEO or ClinVar, and other appropriate databases approved by the consortium and NHGRI.
  • Transferring, in a timely manner, detailed (sequence, variant, other genomic, functional, phenotypic, etc.) and related data and metadata, as appropriate, to the DACC, using agreed-upon formats and processes, to facilitate dissemination of data more broadly through databases such as AnVIL, dbGaP, GEO or ClinVar, and other appropriate databases.
  • Collaborate with the DACC to establish data formats and standards, to track and document collaborations and incoming samples, report findings, etc.
  • Fully disclose data, analyses, algorithms, software source code, and experimental methods to the other members of the consortium for the purpose of scientific evaluation and use by other consortium members.
  • Collaborating with the DACC to track and document collaborations and incoming samples, report findings, etc. in a FAIR (Findable, Accessible, Interoperable, Reusable) manner.
  • Submitting periodic progress reports in a standard format, including metrics of the use and impact on the community, agreed on with the NHGRI Project Scientist/Scientific Officer (PS/SO).
  • Providing reports, summary statistics, and data, as appropriate, in a timely fashion as agreed upon by the PS/SO.
  • Sharing research resources, tools, and data with members of the consortium consistent with achieving the goals of the project.
  • Assess and disseminate data, protocols, consent materials, methods, analyses, models, model parameters, research resources, software, and tools developed for or derived from the DACC within and outside the consortium, as appropriate and according to the release policies developed for and by this project.
  • Abiding by common definitions, protocols, and procedures.

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. NIH will have unrestricted cost-free access and use of the data, resources and software generated by the recipient, including the right to transfer said data and/or software to other NIH-funded and/or managed resource projects, at the NIH's sole reasonable discretion upon termination or expiration of this award.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Project Scientist/Scientific Officer (PS/SO) at NHGRI is a dual role held by a NHGRI Program Director. In the Project Scientist role, the Program Director will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. In the Scientific Officer role, the Program Director will be responsible for the normal scientific and programmatic stewardship of the award and manages concerns about bias as it affects the project. The role of NHGRI PS/SO will be to facilitate and not to direct the activities. The PS/SO will be named in the Notice of Award.

The PS/SO will have the following substantial involvement:

• Serving as a liaison, helping to coordinate activities among and for the recipients, including acting as a liaison to the NHGRI and as an information resource for the recipients about genome research activities. The PS/SO will also coordinate the efforts of the Recipient(s) with other groups conducting similar studies.
• Reporting periodically on the progress of the recipients to the NHGRI Director and to the National Advisory Council for Human Genome Research.
• Assisting recipient(s) in the development, if needed, of policies for dealing with situations that require coordinated action.
• Providing advice on the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed in the course of the award to the scientific community.
• Being responsible for the normal scientific and programmatic stewardship of the award, including assessments of how well the recipient has met any milestones required for each year of funding. 
• Curtailing, withholding or reducing support for any recipient that fails to make satisfactory progress toward the work scope that NHGRI approved, has ethical or conflict of interest issues, or fails to comply with the Terms and Conditions of Award.
• Involving NIH or NHGRI staff who may assist the recipient(s) as designated by the PS/SO.
• Participate in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the IGVF Consortium.
• Negotiate milestones, e.g., throughput, quality, and biological samples with the recipients, as necessary.
• Participate with the other SC members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.

External Scientific Consultants (ESCs): The NHGRI PS/SO may engage external scientists with relevant scientific and consortium experience, who are not funded as part of the project and who agree to a confidentiality policy, to provide input and advice to the NHGRI PS/SO about the project. The PS/SO will appoint scientists as ESCs and will determine the durations of service.  Activities of the ESCs could include:

• Participating, as appropriate, in consortium meetings, Steering Committee calls, and the annual recipients' meetings; a subset of ESC members may also meet remotely at other times during the project period, as needed.
• Reviewing and evaluating the progress of recipients (individually or as a group) in achieving the goals of the project.
• Recommending changes in priorities based on scientific advances within and outside the consortium.
• Providing individual recommendations regarding any changes in the project or grant(s) as necessary.

The PS/SO will consider recommendations from individual ESCs to recommend project changes to the PD/PI, as appropriate.

Areas of Joint Responsibility include:

As there are multiple awards working toward a common goal, close interaction between the participating Recipient(s) and the PS/SO will be required to manage, assess, and implement the common goals of consortium. This is accomplished by:

• Meeting monthly for conference calls to share information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.
• Establishing best practices for data integration and collaborative analyses as appropriate.
• Setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
• Generating responses to ESC recommendations.
• The PS/SO will assist and facilitate the group process and not direct it.
• Steering Committee (SC): The SC will be the main governing body of the Consortium. The purpose of the SC will be to recommend directions for a consortium consistent with achieving the project goals, develop consortium policies to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges and opportunities for the consortium.
• The SC will convene monthly conference calls and yearly in-person meetings to share information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc. As needed, additional meetings of the SC, working groups and consortium members will be determined by the SC.
• The SC will be composed of one representative from each of the grants awarded in consortium. Each PD/PI will decide who will be its representative. Multi-PI grants will have one representative. Each representative will have one vote; The PS/SO will be a voting member. Other designated NIH staff, External Scientific Consultants, or other designated participants may attend the SC meetings on a regular or ad-hoc basis but will be ex officio (non-voting) members.
• The SC will develop its own operating procedures.
• The SC may establish subcommittees or working groups to oversee the development and implementation of consortium policies including data and software releases, publications and standards, etc. Subcommittees or working groups may be either permanent or time limited, may include additional experts, depending on the needs of the research.
• The PD(s)/PI(s) will be expected to play an active role in these subcommittees working groups, as appropriate.
• It is expected that most of the decisions on the activities of the SC will be reached by consensus. If a vote is needed, at least 60% of the voting members must vote in favor of the proposal.
• NIH staff will review and approve policies developed by the SC.
• Recipients will be required to accept and implement policies approved by the SC.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NHGRI may be addressed by convening a Dispute Resolution Panel.  It will be composed of three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement for one award, the first member may be chosen by that recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

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. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

IGVF Program Team
National Human Genome Research Institute (NHGRI)
Email: nhgri-igvf@mail.nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Grants Administration Branch
National Human Genome Research Institute (NHGRI)
Email: nhgrigab@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.