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 Funding Opportunity Announcement.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) 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 Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) solicits applications to develop innovative and generalizable statistical and computational methods for analysis of data from the human Developmental Genotype-Expression (dGTEx) and non-human primate (NHP dGTEx) projects. Methods that assess the influence of genetic variation on development, compare gene expression and regulation across tissues and time points, or leverage comparative genomics to understand developmental and evolutionary processes and integrate with existing tissue and cell atlas efforts are strongly encouraged. This NOFO is open to all applicants regardless of whether they are currently affiliated with dGTEx, NHP dGTEx, or neither.

Background

Many of the factors that influence human health and disease throughout the lifespan are known to be initiated in prenatal and early childhood development. Studies of developmental biology have demonstrated that gene expression patterns are not only tissue-specific but also temporally regulated and controlled through coordinated action of complex networks and pathways. For this reason, it is valuable to study gene expression patterns at a tissue- and cell-specific level over several early development timepoints.

National Human Genome Research Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Neurological Disorders and Stroke and National Institute of Mental Health recently launched Developmental Genotype-Tissue Expression (dGTEx) to characterize transcriptional profiles during human development. dGTEx builds on the Genotype-Tissue Expression (GTEx) Project , which established gene expression profiles within and between human adults across multiple tissues, determining tissue-specific expression as well as associating differences in expression with genetic variation. Thus, the unique attributes and goals of dGTEx are studying gene expression patterns in multiple human tissues during postnatal and juvenile development, defining the role of gene expression in human development, and providing insight into health- and disease-related processes that have their origins before adulthood.

Complementary to the human dGTEx effort, the non-human primate (NHP) dGTEx , funded by NHGRI and the NIH Office of Research Infrastructure Programs, is designed to study gene expression patterns in multiple reference tissues across developmental stages in NHP model species and compare them to human gene expression patterns. NHPs have developmental trajectories similar to humans and therefore are particularly well suited to identify and compare genomic contribution to traits and conditions that are highly developed in humans, such as higher-level cognition, complex social structures, and adaptive immunity. Having comparable data from two NHP species (i.e., representatives of both Old World and New World primates) at different evolutionary distances from humans can enable comparative genomic analyses of development. NHPs are experimentally tractable, providing the opportunity to validate observational findings with follow-up experiments. Unlike many other model systems, NHPs also have high levels of population genetic diversity even in captive populations, making them good model organisms for studies of the impact of genetic variation on developmental processes.

Scope and Objectives

The goal of this Data Integration and Statistical Analysis Methods (DISAM) NOFO is to develop innovative and generalizable statistical and computational methods for analysis of data produced by the dGTEx and NHP dGTEx efforts. Project datasets (including phenotypic and other relevant data) and associated genomic data will be available through the AnVIL starting in Spring 2024 .

The DISAM RFA aims to support the following objectives:

1. Explore the impact of genetic variation on gene expression patterns throughout development.
2. Identify shared and unique gene expression patterns across cells, tissues, species, and development.
3. Integrate developmental data from other species with dGTEx data to better understand developmental and evolutionary trajectories, including considerations of standard vocabularies and ontologies.

Examples of research areas may include, but are not limited to:

• Develop approaches to integrate dGTEx and NHP dGTEx data with publicly available databases (e.g. GTEx portal, UCSC Genome Browser, Ensembl, NeMO Archive)
• Extend existing, or develop new, methods to map expression quantitative trait loci (eQTL) and/or identify allele specific expression, to determine the joint effects of multiple genetic variants on gene expression or cellular composition, to characterize gene expression levels in multiple tissues and time points, and to delineate gene regulatory networks.
• Develop new approaches to make predictions about the functional relevance of genetic variants to gene regulation, in terms of expression levels, gene splicing, and/or regulatory networks, across developmental and evolutionary time points.
• Model static and dynamic eQTLs between different cells/tissues and across age groups.
• Develop new methods that account for genetic diversity of gene regulation across developmental trajectories.
• Develop approaches to integrate multi-model assays (e.g., single-cell RNA seq, ATAC seq, bi-sulfite seq) with bulk tissue analysis from the same donor and across multiple donors.

All methods are expected to be validated using dGTEx/ NHP dGTEx or other available genomic datasets.

National Institute of Mental Health (NIMH)

The National Institute of Mental Health (NIMH) will accept applications that reflect the mission and scientific priorities as identified in the strategic plan NIMH The National Institute of Mental Health Strategic Plan (nih.gov). For the purposes of this RFA, the NIMH has a particular interest in:

• Development of methods for identifying the gene regulatory landscape driving cell-type specific developmental risk mechanisms for psychiatric disorders by integrative analysis of multi-omic data from dGTEx and NHP dGTEx with psychiatric datasets (e.g., PsychENCODE, PGC, etc.)
• Development of comparative genomic and transcriptomic analysis methods for identifying human-specific novel genetic risk mechanisms across early developmental time periods contributing to risk for various psychiatric outcomes
• Development and testing of computational methods to find novel causal effects of genomic and functional omic variation on psychiatric traits by integrative analysis of data from dGTEx and NHP dGTEx with psychiatric datasets (e.g., PsychENCODE, PGC, etc.)

Program Governance and Collaboration

Successful applicants will become members of the dGTEx consortium comprising investigators who have been funded in response to the following NOFOs (RFA-HG-20-039, RFA-HD-21-008, and RFA-HG-21-026). Awardees are expected to work collaboratively with all members towards meeting project goals, in addition to the research goals outlined in their individual applications. Synergies among the different components will be identified by the investigators.

Information on dGTEx and NHP dGTEx consortium members can be found at https://www.genome.gov/Funded-Programs-Projects/Developmental-Genotype-Tissue-Expressionand https://www.genome.gov/Funded-Programs-Projects/Non-Human-Primate-Developmental-Genotype-Tissue-Expression-NHP-dGTEx.

Once awards are made, successful applicants will be asked to collaborate and contribute to developing common plans for analyses of all tissues and single-cell data.

All investigators will be required to attend dGTEx Steering Committee (SC) calls and meetings. The SC comprises the funded PDs/PIs and NIH staff and is charged with guiding the overall scientific direction of the consortium. The SC meets regularly and is complemented by a set of working groups.

Data sharing

Awardees are expected to collaborate with other recipients and comply with the NIH data sharing policies (sharing.nih.gov) and NHGRI’s additional data sharing expectations (https://www.genome.gov/about-nhgri/Policies-Guidance/Data-Sharing-Policies-and-Expectations). NHGRI supports the broadest appropriate genomic, phenotypic, and metadata data sharing with timely data release through widely accessible data repositories. Per NOT-HG-21-022, NHGRI expects applications awarded under this NOFO to share comprehensive metadata and, where applicable, phenotypic data, use standardized data collection protocols and survey instruments for capturing data, as appropriate, and use standardized notation for metadata (e.g., controlled vocabularies or ontologies) to enable future data harmonization and secondary data analyses.

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

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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 Institutions)

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an 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. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

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 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 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 SF424 (R&R) Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jyoti Dayal
Telephone: 301-480-2307
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

All Consortium components are expected to conduct both site-specific and large-scale collaborative analyses and should budget accordingly. Collaborative analyses are expected to be performed on the AnVIL platform. Applicants should budget for costs associated with cloud-based analysis approaches as well as costs related to ensure the data are standardized and harmonized according to the agreed-upon data model. All Consortium components will need to budget for data storage, compute, and egress charges on AnVIL based on Google Cloud Platform pricing. NHGRI will continually assess the utilization of AnVIL

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

. The Data Management and Sharing Plan is expected under the DMS Policy went into effect January 25, 2023..

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The following subsections are recommended:

• Overview
• Research Proposal
• Collaborative Activities

It is not required to use these subsection headings if the applicants feel their proposal works better organized in a different manner. However, applicants are encouraged to carefully consider the goals of the NOFO and the review questions below.

Overview

Provide an overview of the proposal and how it will be structured to achieve the project’s goals. This should include a high-level description of the proposed methods or approaches (e.g., addressing bulk tissue and single cells including choice of computational methods), along with the high-level rationale, with details to be covered in the subsections below. The overview should provide a sense of how the proposed effort will contribute to the understanding or interpretation of tissue specific gene expression including developmental time points and comparison to NHP data. Any planned technical, strategic, methodological, analytical, or other innovation may be highlighted.

Outline the expertise of the research team (without duplicating information in the Biosketches) and explain how their expertise aligns with the key components of the NOFO (e.g., assessing variability, building interpretable models for data, creating tools that are useful for the broader community).

The 2020 NHGRI strategic vision emphasizes that the promise of genomics can t be fully realized without a diverse genomics workforce; diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. As noted in NIH’s Notice of Interest in Diversity (NOT-OD-20-031), scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Therefore, applicants are encouraged to compose teams richly diverse in backgrounds and academic disciplines, including individuals and groups underrepresented in the genomic workforce.

Research Proposal

This section constitutes the bulk of the proposal and should include descriptions of:

• Plans for the project and how it reflects the goals described in the Overview above.
• Approaches for leveraging existing, or developing new, standards to ensure comparability, reproducibility, complementarity, etc. of assay results.
• Plans for adaptability and change given specific details of expected human and NHP dGTEx data may not be available at the time of application submission.
• Innovation and state-of-the-art elements.
• How the research will benefit and enable the wider community.
• Timelines and milestones.

Collaborative Activities

Collaborative activities are crucial for the success of the methods and approaches developed by this NOFO. Applicants should identify, while recognizing that needs will change during the funding period, key analytical challenges they will collaborate. A willingness to work with the Steering Committee needs to be clearly articulated.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Management and Sharing Plan (DMS Plan) as of implementation of the new DMS Policy January 25, 2023. .

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) 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 SF424 (R&R) 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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. 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. Overview Information 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 Policy on Late Application Submission.

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 SF424 (R&R) 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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 SF424 (R&R) 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.

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.

In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Any instructions provided here are in addition to the instructions 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 NHGRI, in accordance with NIH peer review policy and procedures, 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. 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.
• Relevance of the proposed project to program priorities.
• Potential for proposed analyses to address issues of public health importance.
• Potential for proposed analyses to address underserved populations or health disparities.
• Ability of investigative group to complement existing dGTEx expertise and work effectively in large collaborative efforts or consortia.

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 VI. Award Administration Information

1. Award Notices

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. 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, including of note, but not limited to:

• Federal wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 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.

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 (DHHS) grant administration regulations at 45 CFR Part 75 and 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 award 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 the NIH as defined below.

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

• Determining research approaches, designing protocols, setting project milestones, and conducting research.
• Participating in group activities and abide by common definitions, protocols, procedures, etc. as chosen by majority vote of the Steering Committee.
• Collaborating with all human and NHP dGTEx awardee sites in making findings and procedures as widely available and applicable as possible.
• Sharing research resources, tools, and data of interest with members of the consortium consistent with achieving the goals of the project.
• Ensuring that the data, software, resources, materials, etc. produced as part of this project are released appropriately addressed under the Data Management and Sharing Plan under the NIH DMS Policy. Resource Sharing Plan.
• Sharing results according to the Data Management and Sharing Plan..
• 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 and the Steering Committee (SC) for this program.
• Cooperating with other recipients in the development and design of research methods, protocols, tools, and strategies.
• Working productively with NHGRI and with program staff from other NIH Institutes who may be providing co-funding for projects.
• Accepting and complying with study policies established by NIH, and with additional non-conflicting policies approved by the Steering Committee.
• Cooperating with other recipients in the publication and dissemination of program results and the eventual release to the scientific community of methods, tools, and results, and other resources.
• Preparing abstracts, presentations, and publications in a timely manner.
• Assessing and disseminating data, protocols, consent materials, and methods developed within and outside the Consortium.
• Not disclosing confidential information.
• Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee, External Scientific Panel, and the NIH.
• Attending and participating in Steering Committee and other working group meetings and accepting and implementing the decisions, guidelines, and procedures adopted by the Steering Committee, External Scientific Panel, and NIH, as appropriate.
• Interacting with other relevant NHGRI and NIH activities, as needed, to promote synergy and consistency among similar or related projects.
• For the collaboration to be effective, PDs/PIs are responsible for:
  • Ensuring that the recipient receives the appropriate approvals for sharing data with data repositories such as, AnVIL, and other appropriate public databases.
  • Working collaboratively to ensure that detailed phenotypic, environmental, clinical, and related data and metadata is standardized using agreed-upon formats and processes, submitted to the AnVIL to be cataloged, maintained, and made accessible as controlled-access data.
  • Submitting datasets generated from the dGTEx project to public data repositories such as AnVIL, as appropriate and agreed upon with the Steering Committee and NIH.
  • Providing reports, summary statistics, and data, as appropriate, in a timely fashion as agreed upon by the Steering Committee and NIH.
  • Working collaboratively to establish data formats and standards, to track and document collaborations and incoming samples, report findings, etc.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
• Contribute to outreach efforts, including collaborating with other consortia and projects.
• Develop standards and metrics for data, metadata, data quality, and analyses.
  • Contribute all data, metadata, protocols, methodologies, analyses, software, and other products to the Laboratory, Data Analysis, and Coordinating Center and appropriate repositories in specified formats. Software should be shared in alignment with the NIH Best Practices for Sharing Research Software.
• Share best practices and lessons learned with project investigators and external community.

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 be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the program and that NIH staff will be given the opportunity to offer input to this process. The Project Scientist will participate as a member of the Steering Committee and will have one vote. The PS/SO will be named in the Notice of Award and will have the following substantial involvement:

• Participating with the other Steering Committee 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. The Project Scientist will assist and facilitate the group process and not direct it.
• Serving as a liaison, helping to coordinate activities among and for the recipients, including acting as a liaison to the NIH, and as an information resource for the recipients about research activities. The PS/SO will also coordinate the efforts of the program with other groups conducting similar studies.
• Attending all Steering Committee meetings as a voting member and assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The PS/SO will be responsible for working with the Coordinating Center as needed to manage the logistic aspects of the program.
• Reporting periodically on the progress of the program to the Director, NHGRI, and to the National Advisory Council for Human Genome Research.
• Serving as a liaison between the Steering Committee and the External Scientific Panel, attending External Scientific Panel meetings in a non-voting liaison member role, and arranging for timely preparation and distribution of meeting minutes.
• Serving on working groups of the Steering Committee and the External Scientific Panel, as appropriate.
• Assisting recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
• Providing advice in the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
• 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. In the event of a decision to terminate, requiring the recipient to submit a close-out plan within two (2) months of the decision.
• Involving NIH or NHGRI staff who may assist the recipient(s) as designated by the PS/SO.
• Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium/Network decides to publish, participating in data analyses, interpretations, and co-authorship of the publication of Consortium results through their role in scientific program management.
• Establishing best practices for IRB interactions, patient consent or assent (as appropriate), and results reporting, and for collecting, formatting, documenting, and sharing data as appropriate.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and implement dGTEx. In addition to the PD(s)/PI(s), key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.

Steering Committee: The SC will be the main governing body of the Project. The SC will be composed of all the PD(s)/PI(s) of each awarded cooperative agreement in the human and NHP dGTEx program and the NHGRI PS/SO for this Project. Cooperative agreements with multi-PI arrangements will have a single vote to be decided as desired within the multi-PI award. The SC may add additional members, and other government staff may attend the SC meetings as desired. It is anticipated that additional coordination mechanisms may be set up with other U.S. groups that may collaborate with the program. Awardees will be required to accept and implement policies approved by the SC.

The SC may establish subcommittees or working groups, in order to facilitate collaborative work and standardize approaches, or to achieve other goals of the Project. Members may include representatives from the program, other NIH staff and other experts, as appropriate.

The PI(s)/PD(s) will be expected to play an active role in these working groups, which may include (but are not limited to) groups focused on specific cross-project activities, such as data standardization, methods development, outreach and education, or data sharing.

The recipients and the PS/SO will meet as the program SC three times a year (2 in-person and 1 via webinar to meet with the ESP) to share information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.

NIH and the recipients will work with and provide information to an External Scientific Panel (ESP). The ESP will be responsible for reviewing and evaluating the progress of the Project to facilitate members of the Project meeting their individual and collective goals. An NHGRI Project Scientist will serve as the Executive Secretary to the ESP. The ESP will meet at least once a year. During part of this meeting, there will be a joint meeting with the SC to allow the ESP members to interact directly with the awardees. The SC members will receive and consider the ESP’s comments and will provide a written response to the recommendations.

To address particular issues, the Steering Committee may establish working groups, which will include representatives from the program and the NIH and possibly other experts. Recipients agree to work collaboratively to:

• Sharing experiences and expertise across participating awardees and developing consensus approaches to integrating, harmonizing, analyzing, and disseminating data for dissemination to other investigators, the broader scientific community, and NIH-designated databases.
• Establishing best practices for data integration and collaborative analyses as appropriate.
• Inventorying, harmonizing, and analyzing data.
• Developing and refining approaches and evaluate comparability of different approaches.
• Generate responses to ESP recommendations.
• Generate a multidimensional data set that is available to the research community and is interoperable with existing resources.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. 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 the individual 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

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

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.

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. 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

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)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Jyoti Dayal
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-2307
Email: [email protected]

John V. Ilekis, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6895
Email: [email protected]

Amanda Price, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-5224
Email: [email protected]

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

Rudy Pozzatti
Telephone: 301-219-6235
Email: [email protected]

Maricela Trujillo
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-7716
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: [email protected]

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 45 CFR Part 75 and 2 CFR Part 200.