Part 1. Overview Information

Key Dates

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the 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

The National Human Genome Research Institute (NHGRI) will renew the Human Genome Reference Program (HGRP). This NOFO will establish the Human Pangenome Coordinating Center (herein Coordinating Center ) a component of the HGRP, which will include two other components: High Quality Reference Genomes (herein Genomes Center ) and Informatics Tools for the Pangenome (herein Tools Projects, see Companion Funding Opportunities). The Coordinating Center will serve as the logistic and scientific hub for the HGRP and will create, improve, release, maintain, and facilitate adoption of a human pangenome reference.

The overall goal of the HGRP during the renewal is to produce a human pangenome reference that optimizes both the genetic diversity represented, along with the utility for, and adoption by, the genomics research community. Awardees under all three NOFOs will work collaboratively within a consortium towards production and community adoption of the human pangenome reference.

This is a limited competition RFA. Only recipient organizations funded under RFA-HG-19-004 are eligible to apply.

Background

A human genome reference sequence is an accepted representation of the human genome used as a standard to align and assemble genome sequence data. It also serves as a consensus coordinate system for reporting results. Since the completion of the Human Genome Project, the genome reference has been steadily improved by resolving errors and adding information from new assemblies. Improved or updated reference versions are curated and released to the community by the Genome Reference Consortium (GRC), a collaboration between the National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI). The existing reference, however, has limitations including assembly gaps, lack of haplotype resolution, and most importantly inadequate representation of genetic diversity, which perpetuates reference bias and risks exacerbating health disparities across populations.

The HGRP was established in 2019 by the National Human Genome Research Institute (NHGRI) to improve the human genome reference by using new methods for more complete assemblies, and by increasing genetic diversity. HGRP-funded investigators formed the Human Pangenome Reference Consortium (HPRC), which over the last three years added high-quality genome sequence assemblies with diverse genetic ancestries to the reference (with a target of 350 total assemblies over five years) and built computational representations of this multi-genome reference (termed the pangenome ). In 2023, the HPRC released the first pangenome draft assembled from nearly 50 diverse genomes represented as a graph, established an embedded ethical, legal, and social implications (ELSI) team which guided the HPRC on issues such as consent and participant community engagement, and initiated collaborations with international partners to develop a resource representative of global populations. These efforts constitute a strong foundation for the further improvement of the human pangenome reference.

In October 2022, NHGRI hosted a workshop to identify future directions for the HGRP. The report from this meeting can be found here. Meeting participants strongly encouraged the continuation of the program, with key recommendations emerging from the participants individual input including:

• Prioritize utility over quantity and focus on sample selection and data generation of highest benefit to the broader genomics research community.
• Emphasize adoption of the new pangenome by identifying use cases, building user-friendly tools, and minimizing disruption to existing workflows.
• Establish partnerships with international organizations and global participant communities and strive to ensure equitable benefit of the pangenome.
• Integrate ethical, legal and social implications (ELSI) at all stages of research including project design, recruitment, adoption, dissemination, and access.

Considering these recommendations, NHGRI proposes to renew the HGRP. The goals for the renewal include: 1) continuing to maintain and improve the pangenome reference, including generation of 200 additional diverse, reference quality sequence assemblies; 2) facilitating adoption of the pangenome reference by the research and clinical genomics communities; 3) fostering the development and deployment of informatics tools for the pangenome; 4) embedding ELSI research; and 5) forming international partnerships to maximize the chances that the human pangenome reference will represent populations worldwide, and encourage the collaboration of scientists worldwide in its creation and use. Overall, there will be a shift in emphasis towards evaluating HGRP progress in terms of how useful the pangenome resource is for clinical and basic genomics researchers. Based on the input we received at the workshop, the overall goal of the HGRP during the renewal will be to produce a human pangenome reference that optimizes both the population genetic diversity represented, and also the utility for, and adoption by, the genomics research community.

Based on the subsequent Concept for this program presented to the National Advisory Council on Human Genome Research the components of the renewal will be:

1. High Quality Reference Genomes ( Genomes Center, see RFA-HG-23-024), a limited competition NOFO that focuses on generating high-quality human genome sequence data and assemblies to fill gaps in genetic variation and diversity, and includes the embedded ELSI component.
2. Human Pangenome Coordinating Center ( Coordinating Center, this NOFO; RFA-HG-23-025), a limited competition NOFO that will serve as the logistic and scientific coordinating center for the HGRP and will create, improve, release, and maintain new pangenome reference versions and organize community outreach and resource adoption.
3. Informatics Tools for the Pangenome ( Tools Projects, see RFA-HG-23-026), consistent with the overall emphasis of the renewed program on utility and adoption, this NOFO is an open competition that will fund multiple investigators to develop computational tools to addresses the need to facilitate uptake and use of the pangenome reference with an emphasis on tools for common use cases of the pangenome relevant to broad sectors of the genomics community.

All awardees of these NOFO’s are expected to work together closely to achieve the goals of HGRP.

The renewal of the HGRP will not include a specific NOFO for further development of pangenome reference representations; we expect that continued work on development of reference representations will occur through NHGRI’s regular investigator-initiated programs. NHGRI will also encourage other complementary investigator-initiated research related to the pangenome (see Concept Clearance document and slides). Where appropriate, these investigators will become members of the consortium (e.g. through associate membership).

Objectives

The Coordinating Center will organize outreach efforts to international partners, researchers, and participant communities from diverse populations to create a globally inclusive pangenome resource.

The Coordinating Center will also develop state-of-the-art, multi-use reference representations of the pangenome. These representations will be part of a larger set of computational tools that will form the core infrastructure supporting the use and adoption of the pangenome resource. The Coordinating Center will continue to work with other human reference groups to annotate, update, and maintain the pangenome for a broad user base including basic scientists and clinicians. To pilot the use of a new human pangenome reference, the Coordinating Center will identify and partner with ongoing genomics consortia that will serve as early adopters of the pangenome and work with those groups on specific projects to determine the added scientific and clinical value of using the pangenome reference. Finally, the Coordinating Center will oversee the logistics of the HGRP by organizing meetings, tracking progress and publications, and establishing protocols and processes for communications and collaborations within and outside the consortium.

The overall goal of the HGRP renewal is to produce a human pangenome reference that optimizes genetic diversity, along with the utility for, and adoption by, the genomics research community.

The Coordinating Center will be a core component of the HGRP. It will:

1. Integrate and coordinate with and between the other HGRP elements to ensure the consortium works cohesively.

The Coordinating Center will foster discussion within the consortium, and with outside experts as needed, to ensure the overall project is meeting its goals and milestones. The Coordinating Center should facilitate HGRP-wide discussions and decision making on: 1) the desired tradeoffs between quality and quantity of assemblies in the pangenome as identified by the Genomes Center; 2) addressing issues raised by the Genomes Center’s embedded ELSI team related to identifying, consenting, collecting, and sharing data from diverse global populations; 3) working with the Tools Project and with early adopting partner consortia to identify whether additional samples and/or specific tools are needed by disparate user communities in order to create a broadly useful pangenome tool kit that facilitates uptake and adoption of the new reference (see #3 below).

2. Explore, select, and implement state-of-the-art reference representations, building on the progress made on graph representations.

The Coordinating Center will identify data structures representing the pangenome reference that serve a large user community with different needs (e.g., novel variant discovery, association analyses, functional genomics, population genetics). Consideration should be given to 1) whether multiple representations are needed; 2) how these and existing representations are compatible with a stable common coordinate system; 3) what type of genetic and genomic information is represented; 4) which representations facilitate version updates and liftovers and when such updates are needed; and 5) which use cases are graph or linear representations ideally suited for. Special attention should be paid to how the informatic complexity of pangenome representations may serve as a barrier to novel tool development and wide adoption of the reference.

3. Develop a basic tool infrastructure and aggregate key pangenome tools.

The Coordinating Center will be responsible for developing the basic computational and informatic infrastructure enabling broad, flexible use of the human pangenome reference. This infrastructure should consider data storage and access in a federated system with different levels of data restrictions, liftover capabilities with other reference builds, reference annotation, version control, user experience (UX) design (e.g., user interfaces, visualizations), computing costs, scalability, and maximizing the overall usability and functionality of the reference. The Coordinating Center will work with the Tools Project to aggregate and track specific user-centered tools and applications into a centralized, open-access repository.

4. Coordinate with other groups to annotate, QC and engage in other activities needed to release a useful reference to the community.

The Coordinating Center will collaborate with other funders and resources that have a direct role in genome references, especially GRC, NCBI, The Wellcome Trust, and EBI to annotate, update and maintain the pangenome reference. The Coordinating Center will also work with other organizations that set standards (e.g., Global Alliance for Genomics and Health (GA4GH)) to ensure the pangenome reference complies with widely used data standards and, where appropriate, contributes to the development of new ones. Additionally, the Coordinating Center will liase and collaborate with other efforts that provide resources of genomic variation (e.g., ClinVar, ClinGen, gnomAD, HGSVC) and function (e.g., IGVF, dGTEx) to help work towards a harmonized and integrated representation of human genetic variants and their functional impact. These interactions and collaborations will be essential to the success of the human pangenome reference.

5. Engage with different broad sectors of the research and clinical communities to accelerate adoption of the pangenome reference.

The Coordinating Center will reach out to and engage with different user communities (e.g., population geneticists, functional genomics researchers, molecular biologists, medical geneticists, clinicians, genetic counselors) to identify their needs for and ability to adopt a new pangenome reference. Special emphasis should be placed on identifying barriers to adoption and any strategies to overcome them. User community needs and adoption should be a common consideration for all Coordinating Center activities.

6. Identify and oversee adopter projects of the pangenome reference.

The Coordinating Center will identify and partner with existing genomics consortia that will be early, and immediately most impactful, adopters of the pangenome reference. Together they will identify and address challenges to adoption, and develop coordinated projects that collect data on, and develop metrics for, the scientific and/or clinical value of adopting the pangenome reference. The adopter projects should represent the breadth of science and medicine that rely on genetic and genomic data and may make use of the pangenome.

7. Coordinate outreach to international partners, research collaborators, and participant communities with the larger goal of creating an inclusive and representative resource.

The Coordinating Center should facilitate collaborations across international stakeholders (e.g., funders, health ministries, non-governmental organizations, scientific societies) to identify and meet the needs of the global scientific and medical communities. Special emphasis should be placed on engagement and partnership with populations and regions typically underrepresented in large-scale genomics efforts such as the global south. Together with the embedded ELSI component of the Genomes Center, these collaborations should address key issues in data sharing and sovereignty, engagement and trust with diverse communities (e.g., indigenous populations), lowering barriers to access, scientific independence, user training and education, equity and health disparities, as well as establishing a pathway for maintaining and sustaining the pangenome as an international resource in the long-term.

8. Oversee logistical coordination of the HGRP.

The Coordinating Center will facilitate interactions and communications within the consortium, with partnering adopting consortium, and with user and participant communities. The Coordinating Center will 1) schedule/host conference calls and oversee meeting logistics; 2) take meeting and call notes and record/follow up on major action items; and 3) maintain an internal web site, Wiki, or similar platform for communicating, retaining and tracking key program documents, policies, and action items. The Coordinating Center will also organize and support consortium meetings and meetings with partnering organizations and adopter consortia, as well as working with and developing processes for responding to feedback from external scientific consultants.

Objectives 5-7 are anticipated to require a high degree of user and participant community engagement, an ability to productively lead collaborations with a wide range of consortium members and outside members of the research community spanning interest areas (both basic and clinical research) and various levels of user expertise. Overall, the HGRP is intended to realize the vision from the October 2022 meeting to significantly improve the human pangenome reference by representing as much human genetic variation as needed to meet disparate scientific and clinical applications while engaging with international partners and the global research community to provide a widely accessible and easily usable genomic resource.

Center management and integration with the consortium. The project management structure should ensure the efficient planning, initiation, implementation, and timely completion of all activities and day-to-day oversight of the activities, with clear mechanisms for decision-making and strategies for resolving disagreements within the Coordinating Center or broader HGRP, particularly in situations where consensus cannot be achieved. Specific timelines and milestones should be developed and updated as needed, in collaboration with the other HGRP recipients, NHGRI staff, a consortium Steering Committee (see below), and any external scientific consultants (see below) to the program.

Work under this NOFO should be closely integrated with the work done under the companion NOFOs to ensure that the higher-level goals of the HGRP towards producing a useful community resource are realized. The governance and project management structure and plans of the Coordinating Center must reflect this.

Project management should involve frequent interactions and communications with NHGRI staff, including hosting site visits and preparing additional reports as requested by NHGRI staff. Finally, the project management structure should ensure efficient engagement with other consortia, for example those using the data, and those developing improved sequencing and assembly methods.

The HGRP as a whole will include a Steering Committee, composed of representatives from all funded awards under this program (see Terms and Conditions), which will meet on a regular basis (at least monthly) to discuss and evaluate progress and challenges, form and revise working groups as needed, and otherwise coordinate activities across the consortium. Major decisions affecting the output of the consortium (including e.g., criteria and priorities for sample selection; data quality and incorporation of new sequencing platforms or assembly methods ) must be approved at the Steering Committee level.

The HGRP is expected to recruit external scientific consultants (ESCs) who can, based on their individual expertise, assess different aspects of the program’s operations, scientific progress, and plans. Assessments from individual ESCs will be made available to the Steering Committee and NHGRI staff. ESCs will have expertise in a broad range of topics relevant to genomic medicine and genomic research including genomic technologies, computational genomics, data science, cloud computing, data management, data sharing concerns (such as participant protection issues), and ELSI issues. ESCs must be approved by NHGRI program staff; NHGRI may require additions to the ESCs to balance expertise. Any ESCs who have been already providing input to the applicants regarding pangenome reference-related work should be listed in the application; however, applicants should refrain from recruiting or naming any additional ESCs until after the new program is funded.

Data and resource sharing in this Initiative. Consistent with achieving the goals of this program, NIH expects that all products of the HGRP will be appropriately made available to the community. This includes (but may not be limited to):

• Sequence and metadata for the high-quality genomes, publicly available and unrestricted for use (with specific exceptions approvable by NHGRI for e.g., data from international collaborators).
• Protocols, software/informatics tools, and quality standards developed for producing high-quality genome assemblies, particularly for newer platforms.

Awardees are expected to comply with the NIH Genomic Data Sharing Policy and the NHGRI Genomic Data Sharing Policy. Collaborative environments, such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL), should be considered for data sharing.

Because the overall goal of the HGRP will be to produce a community resource, Resource Sharing and Data Management and Sharing Plans will be included in the consideration of the priority score. After initial review, NHGRI program staff will conduct an additional administrative review of any plan for sharing data and resources and may negotiate modifications of the Resource Sharing and Data Management and Sharing Plans with the prospective awardee. The final negotiated version of the Resource Sharing and Data Management and Sharing Plans will become a term and condition of the award of the cooperative agreement.

Plan for enhancing diverse perspectives.

The NIH recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. There are many benefits that flow from a diverse 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 populations participate in, and benefit from research, and enhancing public trust.

• To support the best science, the NIH encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:
• Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics.
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Individual applications and partnerships that enhance geographic and regional heterogeneity.
• Investigators and teams composed of researchers at different career stages.
• Participation of individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Opportunities to enhance the research environment to benefit early- and mid-career investigators

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material.

Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation .

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not 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 registration; 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 his/her 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

Only one application per institution (normally identified by having a unique entity identifier (UEI) number or NIH IPF number) is allowed.

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 or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing a multi-component application.

Overall Component

When preparing the application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

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

Other Attachments:

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse backgrounds, including those from underrepresented groups in research.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

PEDP implementation costs:

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims: Specific Aims should convey the entire planned effort.

Research Strategy: The Overall Human Pangenome Coordinating Center research strategy section should provide a scientific vision for, and integrated overview of, how the proposed center would accomplish the objectives of this NOFO toward creating, providing, and maintaining a state-of-the-art human pangenome reference for multiple user communities with varying degrees of scientific and clinical goals and different levels of technical expertise. Applicants should discuss key decision points and trade-offs, including how they would prioritize scientific and practical choices (e.g., resource allocation between center components, when to release new reference builds, prioritization and selection of new genomes for the reference). Applicants should also discuss how they will work collaboratively with the other HGRP awardees to ensure compliance with the NIH data sharing policies and NHGRI’s expectations which are summarized at www.genome.gov/data-sharing. Applicants are encouraged to propose creative and practical ideas to attain the larger goals of this NOFO as set out in the Funding Opportunity Description, particularly working with international partners to establish an equitable global resource representative of the world’s populations. This section should also include:

• A high-level view and outline of a strategy for transitioning the current human reference representation to a pangenome representation, considering that the current representation (e.g., GRCh38) will be in use until (at least) a transition is complete. This strategy should consider how to track updates, version control, and whether multiple, use-dependent representations are needed.
• An overall view of the proposed Coordinating Center, including management of the Coordinating Center components and reporting relationships. NHGRI anticipates that responses to this NOFO are likely to be multi-PI applications. This view should convey how the Coordinating Center will operate as a whole.
• An overall view of how the Coordinating Center will work with other NHGRI HGRP components, including the Genomes Center (which will provide high quality human genome assemblies) and the Tools Project (which will develop user-centered pangenome tools). This HGRP-wide coordination includes working on sample prioritization and selection and tool integration and dissemination, respectively, as well as soliciting and incorporating research community feedback to facilitate wide adoption of the pangenome reference.
• A plan for working with the ELSI component funded under the Genomes Center and ensuring it is successfully embedded in all aspects of the consortium. Applicants should describe their experience and expertise to facilitate addressing ELSI issues across all components of HGRP.
• An overall view of how the Coordinating Center will work with other US and international efforts that produce the human genome reference in a way that effectively delivers the genome reference resource to the community. The application as a whole should convey how different parts fit together and will be coordinated, even if some are funded by other means. For example, the Coordinating Center will need access to computational resources to store, compute on/synthesize, and serve the reference. Applicants may propose to use grant funds for this, or may collaborate with existing informatics resources/facilities such as NCBI and the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL).
• A plan to collaborate with groups producing other large-scale genomic resources that may augment the usefulness and impact of the reference. Such resources may include efforts cataloging genetic variation (e.g., ClinGen, ClinVar, HGSVC, gnomAD) and function (e.g., IGVF, dGTEx). See also Project 2 for establishing adopter consortia. NHGRI encourages these interactions because they represent ways to improve presentation and adoption of the reference, improve its sustainability, and will leverage NHGRI’s existing investments.
• A description of how the Coordinating Center will approach key decisions such as prioritization and incorporation of diverse human genome assemblies into the reference from all appropriate sources. Applicants should describe their plans for, in coordination with the Genomes Center, facilitating developing and tracking metrics of diversity (e.g., genetic, geographic ) and adopting the appropriate language to describe participant communities (see the National Academies report on Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field). Applicants should understand that final decisions on these questions will be made in concert with all of HGRP.
• A view of how the Coordinating Center will liaise with other relevant genomic data resources and consortia. The application should state and justify the priorities for such collaborations, e.g., with reference to their ability to provide a comprehensive view of human variation, demonstrate the potential practical uses and applications of the pangenome reference, or engaging with a diverse population of participants or user communities.
• A description of "added value" products and how the Coordinating Center will release or otherwise provide these products to the research community. Deliverables should include general infrastructure tools (see Project 1) and application-specific tools (see Tools Project RFA-HG-23-026) and should take into account user community feedback (see Project 2). Because the high-level goal of the HGRP is to construct and provide a community resource, plans for sharing research products, including the Resource Sharing Plan, will be considered in the priority score.

Several of the objectives of this NOFO require a high degree of engagement with the research community, and the ability to productively lead collaborations with a wide range of consortia and members of the research community spanning basic and clinical interests and different levels of user expertise. Applicants should include evidence of past successful experience in this area.

Letters of Support:

Applications should include letters of support from proposed collaborators, especially if they will be integral to the overall plan for the Coordinating Center.

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.

In addition, for this NOFO, the Resource Sharing Plan should provide an overview of how all products of the research will be made available, and how the availability or use of those products will be facilitated especially in the context of the new program emphasis on adoption of the pangenome reference. Where details are provided in the relevant sections of the Research Plan, the Resource Sharing Plan should refer to them rather than duplicate them here. Resource sharing is an integral part of developing a community resource such as the pangenome reference; resource sharing plans will be considered in the overall priority score.

For the Resource Sharing Plan, applicants should discuss:

• How any research tools (including informatics analysis or data processing tools) and new methods developed under this award will be made available. For this NOFO, tools, methods, and software should be well-documented and, where applicable, should be made available via version-controlled public repositories. See list of frequently asked questions about Best Practices for Sharing Research Software .
• How protocols and quality standards that were developed for producing reference representations will be made available.

After initial review, NHGRI program staff will conduct an additional administrative review of any plans for sharing resources and may negotiate modifications of those plans with the prospective awardee. The final negotiated version of the plans will become a term and condition of the award of the cooperative agreement.

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. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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.
• Recipients must comply with the NIH Data Management and Sharing Policy (NOT-OD-21-013) and NIH Genomic Data Sharing Policy (NOT-OD-14-124). NHGRI supports the broadest appropriate data sharing with timely data release through widely accessible data repositories. Please follow the NIH guidance on writing a Data Management and Sharing (DMS) Plan here, and ensure the Plan is in alignment with NHGRI’s data sharing expectations, which are summarized at genome.gov/data-sharing.
• Data management and sharing is an integral part of developing a community resource such as the pangenome reference; Data Management and Sharing Plans will be considered in the overall priority score.

The Data Management and Sharing Plans should not duplicate (but should refer to) details about data sharing that are explained elsewhere in the Research Plan.

The Data Management and Sharing Plan should address:

• How applicants will share appropriate sequencing metadata, with a focus on existing or emerging standards for FAIR (findable, accessible, interoperable and reusable) genomic data.
• How all data (including sequence, assembly, variant, other) for the high-quality genomes will be made publicly available for unrestricted use in a timely manner consistent with NIH policy.
• Applicants should discuss how samples are consented for such use.
• If applicants propose any work on samples or data where the consent does not allow open release (eg, particularly scientifically valuable samples from international collaborations or indigenous communities), how those data will be made available to the community. Note that work on any samples that do not allow fully open release without restrictions must be approved by NHGRI.
• Where data will be made accessible, including, but not limited to the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL).
  

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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 (Overall)

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

Project 1: Human Pangenome Reference

When preparing your application, use Component Type Project 1

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

SF424 (R&R) Cover (Human Pangenome Reference)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Research & Related Other Project Information (Human Pangenome Reference)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Human Pangenome Reference)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Human Pangenome Reference)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Human Pangenome Reference)

Resource Sharing

Data Management and Cost budget should include any funds required to support sharing of genomic data under this NOFO (e.g., to prepare the data for submission to appropriate repositories).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Human Pangenome Reference)

Specific Aims: Provide the aims for building, maintaining, and providing the human pangenome reference.

Research Strategy: This Project research strategy should focus on scientific, technical, and logistical details about how the human pangenome reference will be constructed, maintained, improved, and provided to a community of users with different needs and levels of expertise. The strategy should include the details and specifications of a flexible, scalable, and robust computational and informatic infrastructure addressing the current and anticipated needs of the pangenome reference user communities. It may include, for example:

• Plans for maintaining the reference, e.g., correcting errors, making updates, ensuring backwards compatibility, releasing new versions, and providing stable coordinates.
• Plans for evaluating the quality of the reference. This includes computational/analytic capabilities and sequencing technologies that will be required to resolve errors, ambiguities or remaining gaps in the pangenome reference.
• Plans for how the pangenome reference will be represented and made available to a broad community of users with varying levels of experience and needs, including details about analytical methods and expertise needed for different applications. Plans should account for the near-term needs to serve the reference in its current representation (e.g., GRCh38), as well as a transition to improved representations especially in response to user feedback (see below) and to minimize disruptions to existing workflows. Describe any computational resources and expertise needed to store and compute on data, serve the reference, etc., whether data resources are to be supported by grant funds or through other means.
• Plans to identify the data structures and representations that meet the needs of different user communities (e.g., population, functional, clinical genomics). These plans should address whether multiple representations are needed for different applications; how these representations are compatible with a common coordinate system; what type of genetic and genomic information is represented (e.g., types and frequency of variants, genome topology); how and by whom the reference is annotated and how those annotations are carried over from previous and to new builds; and what types of representations (e.g., linear vs graph) are best suited for different use cases. Applicants should keep in mind that one of the main goals for the HGRP renewal is to prioritize utility and adoption of the resource by basic researchers and clinicians that use genomic data.
• Plans for incorporating user experience and feedback into updates and improvements of the pangenome reference. This includes results from early adopter projects, individual tools developed by the Tools Projects (RFA-HG-23-026), as well as information garnered from the general research community and investigator-initiated projects.
• Technical and strategic plans for incorporating new genomes into the reference, including new assemblies produced by the Genomes Center, international partners, or other sources as well as the minimal quality standards that will be applied. Applicants should discuss and justify their view of how new genomes should be prioritized and what metrics should be developed to track progress and versions of the pangenome.
• Details of how, in coordination with the Genomes Center’s embedded ELSI component, issues related to the prioritization of genomes to be incorporated into the pangenome as well any issues related to the release and accessibility of the pangenome resource will be considered and addressed. In particular, there should be a plan for incorporating high priority genomes from individuals that have not consented to full open access.
• Plans for building a flexible and adaptable set of tools, environments, and processes that will serve as the core infrastructure supporting a variety of tools and applications geared towards a broad user base of researchers and clinicians across a wide range of technical expertise. This plan should consider user experience and interfaces as well as general functionality and usability of the pangenome resource.
• Plans to develop or adopt a federated system of data storage and access that considers data restrictions and sovereignty while maintaining a democratized, widely accessible, and open-access resource.

Letters of Support:

Applications should include letters of support from proposed collaborators, especially if they will be integral to the overall plan for Project 1.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Human Pangenome Reference)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Project 2: Community Outreach and Adoption

When preparing your application, use Component Type Project 2.

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

SF424 (R&R) Cover (Community Outreach and Adoption)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Research & Related Other Project Information (Community Outreach and Adoption)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Community Outreach and Adoption)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Community Outreach and Adoption)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Community Outreach and Adoption)

Budget forms appropriate for the specific component will be included in the application package.

Adopter project costs

Budgets should include support for adopter projects with partnering genomics consortium. How costs will be distributed between the Coordinating Center and the adopter consortia should be indicated.

Outreach

Budgets should include support for outreach activities including travel for PD(s)/PI(s) and any key personnel to 2-3 international meetings over the course of the award to meet with international partners and stakeholders.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Community Outreach and Adoption)

Specific Aims: Provide Aims for outreach to potential international partners, research and clinical users, and diverse participant populations.

Research Strategy: Describe how the Coordinating Center will engage and partner with international researchers and organizations that will contribute to the assembly, maintenance, and dissemination of the pangenome reference. Also provide information on how user community needs (e.g., from basic population genetics to interpretation of patient genomes) will be identified and responded to while keeping in mind varying levels of user expertise. Special attention should be given to identifying a community of users that will benefit from early adoption of the pangenome and identifying corresponding consortia to partner with. Finally, provide a plan for raising awareness, disseminating tools, and educating the research community and public on the pangenome reference.The overall strategy should clearly lay out the significance and effectiveness of proposed plans.

This section should include:

• A plan for how international partners will be identified and selected and the specific goals and terms of those collaborations. Special emphasis should be placed on how these partnerships will be equitable, how they will respond to specific user and participant community needs, and how they will foster scientific and intellectual contributions from all those involved. Consideration should be given to any needs for supporting infrastructure and ensuring the democratization of the pangenome resource.
• A framework for identifying and working with existing genomics consortia to establish early adopter projects that may determine the added scientific or clinical benefit of using the pangenome reference. Examples of specific consortia or datasets may be identified but projects selected should reflect the range of potential user needs (e.g., population genetics, functional genomics, clinical genetics), and a general framework should be provided for expanding beyond the proposed list to include other groups over time and in consultation with the consortium steering committee, external scientific consultants, and user community feedback.
• How traditionally underrepresented populations and participant communities in genomics research will be identified for engagement and how any ELSI concerns or issues with contributions to or potential misuses of the pangenome reference will be addressed. Plans should include how the Coordinating Center will work with the embedded ELSI component of the Genomes Center in considering these issues.
• How participant communities underrepresented in human genetics studies such as indigenous populations and populations from the global south will be engaged and their needs identified and addressed.
• How applicants plan to conduct outreach to researchers from diverse backgrounds, including those from underrepresented groups in the genomics workforce and how lower resourced institutions conducting research will be identified, engaged, supported, and partnered with to promote a diverse community of researchers that contributes to and delivers a widely accessible resource.
• How surveys, user focus groups, workshops, or other means will be used to identify specific user communities, understand their needs, and incorporate those needs into ongoing priorities for the reference.
• A plan for using in-person education, training, and information sessions (e.g., webinars, seminars, workshops, education sessions) tailored to specific user communities at various career stages to inform them of the use, functionality, and significance of the pangenome reference.
• A plan for indexing, aggregating, or using repositories for pangenome informatic tools developed by HGRP as well as user communities.
• A plan for using statistics, metrics, and other means to track and understand the uses and users of the reference.

Applicants are encouraged to think creatively about how to make the most efficient use of the resources available, especially for user outreach and training activities.

Letters of Support:

Applications should include letters of support from proposed collaborators, especially if they will be integral to the overall plan for Project 2.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Community Outreach and Adoption )

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Project 3: HGRP Logistical Coordinating Center

When preparing your application, use Component Type Project 3.

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

SF424 (R&R) Cover (HGRP Logistical Coordinating Center)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (HGRP Logistical Coordinating Center)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (HGRP Logistical Coordinating Center)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (HGRP Logistical Coordinating Center)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (HGRP Logistical Coordinating Center)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (HGRP Logistical Coordinating Center)

Project Management

Budgets should include support for a dedicated Project Manager who will devote a minimum of six person months, based on a 12-month calendar, to oversee the day-to-day activities of the Coordinating Center, coordinate across HGRP components, if applicable, and be responsible for promptly providing requested reporting information to NHGRI Program Staff. A PD/PI may serve as the Project Manager.

Consortium Meetings

Budgets should include support for annual in-person consortium meetings (approximately 200 participants) to fully cover costs of planning, meeting facilities and logistics in accordance with applicable NIH policy, and travel and accommodations for members of the External Scientific Consultants (5 people).

Budgets should include support for in-person, mid-year Steering Committee meetings in years 1 and 2 (approximately 50 participants) to fully cover costs of planning, meeting facilities and logistics in accordance with applicable NIH policy.

Budget should include funds for the PD(s)/PI(s) and key personnel to attend the initial consortium kickoff meeting, the annual consortium meetings thereafter, and, if appropriate, mid-year Steering Committee meetings.

Consortium Communications

Budgets should include costs for establishing and managing web-based conference and communication platforms. Web conference resources should allow for at least monthly Steering Committee meetings, consortium web conferences, and bi-weekly working group web conferences.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (HGRP Logistical Coordinating Center)

Specific Aims: Provide the aims for logistical coordination of the HGRP.

Research Strategy: Describe how the Coordinating Center will serve as the logistical coordinating center for the consortium. This should include:

• Plans for facilitating communications within the consortium; scheduling/hosting consortium conference calls, meeting logistics; taking meeting and call notes and recording/following up on major action items; maintaining an internal website, Wiki, or similar platform for communicating, retaining and tracking key program documents, policies, and action items.
• The HGRP collectively is expected to recruit external scientific consultants (ESC, see Cooperative Agreement Terms and Conditions) who can assess the Program’s operations, scientific progress (according to the overall goals of the program), and plans. Applicants should include a plan for how the Coordinating Center will, in coordination with other HGRP components, identify (e.g., desired expertise) and recruit an ESC and develop processes for responding to and addressing issues or concerns and incorporating feedback and advice provided by them.
• A plan for organizing and supporting an annual consortium meeting, including supporting travel for up to five external scientific consultants to the annual meeting.
• A plan for how the Coordinating Center will work with consortia of adopter projects to facilitate use of the pangenome reference and respond to any project-specific needs that may arise. This may require organizing and supporting joint meetings with partnering consortia. The plan should also include how the Coordinating Center and adopter consortia will identify and respond to any barriers to adoption, troubleshoot, and incorporate lessons learned to ease transition to the new reference by the broader research community.
• A plan for tracking publications and presentations of the program and maintaining a library of presentations including materials that can be re-used by consortium members.
• A plan for innovations or improvements in coordination, communication, protocols, and processes within the consortium as well as its interactions with outside partners.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (HGRP Logistical Coordinating Center )

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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) using ASSIST or other electronic submission systems. 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.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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.

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.

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.

Significance

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

Does the application present a coherent vision for how the center will produce, provide, improve, maintain, and disseminate as well as transition to a broadly useful and easily accessible human pangenome reference?

Does the proposed project address the needs of the HGRP including coordinating with different HGRP elements and outside partners as well as incorporating their feedback? Is the scope of activities proposed for the project appropriate to meet those needs?

Is the overall plan likely to result in a resource that is widely adopted, and that appropriately balances the diverse needs of a broad genomics community?

Has the application adequately and creatively considered the opportunities for working with partners to present the genome reference to the community in a way that will be most useful, for example working with other genomics consortia and international organizations?

To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

Investigator(s)

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

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

Innovation

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

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Is the overall center management plan adequate? Does it provide a coherent view of how the multiple elements of this application will be coordinated and managed?

Does the overall plan convey how the investigators will work towards a practical realization and wide adoption of a human pangenome reference? Does the high-level plan for transitioning from the current representation to a future pangenome representation take into account both the scientific factors and community outreach needs?

Does the application identify the key partners and address how the center will coordinate with other US and international efforts that work to produce the human genome reference? Is there a high-quality plan for successful coordination between collaborators funded by other sources, and with other NHGRI and NIH programs?

Does the application identify adopter projects that will have an immediate impact in evaluating the utility of adopting the human pangenome reference?

If the applicant has identified key partners to undertake a critical element of the overall plan for this specific NOFO, are those roles clearly defined and are they likely to be successful? Is the plan adequate for coordinating with other entities involved in producing genome references?

Has appropriate consideration been given to groups working on standards and policies relating to references, etc. (this could include, for example, GA4GH ?

Has the applicant identified the major issues, choices, and trade-offs involved in producing a high-quality and broadly useful pangenome reference and serving it to the community? Does the application provide a clear view and justification of stated priorities?

Is the Data Management and Sharing Plan sufficient to address the goals for a broadly useful and accessible human pangenome resource?

Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Overall Impact - Project 1: Human Pangenome Reference

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

Scored Review Criteria - Project 1: Human Pangenome Reference

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

Significance

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

Investigator(s)

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

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are plans for maintaining and improving the human reference, such as correcting errors, making updates, providing new version releases adequate?

Are plans adequate for how the reference will be constructed, represented, and made available to the research community? Are resources, including computational resources, adequate?

Are plans for identifying data structures and representations that meet the needs of different user communities adequate? Do these plans address what type of representations are needed, what type of genetic information is represented, what common coordinate system is used, how lift over capabilities are built in, and how annotations are completed?

How well are the detailed plans for this project related to the long-term goal of a practical representation of the human pangenome reference? Are plans adequate for the short-term maintenance of the current representation, and the transition to a pangenome reference? Is there sufficient description of alternate representations depending on user needs?

Are there adequate plans for evaluating the quality of the reference, including evaluation and resolution of errors or ambiguities especially from existing gaps in the current draft pangenome reference?

Are plans adequate for making the reference versions "backwards compatible" or version independent and do they otherwise minimize disruption for the community to switch to new reference versions when they are released?

Are plans adequate for developing a basic informatics infrastructure that will support user tools that are openly accessible to a broad community of users?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Does the overall plan provide for adequate computational resources to provide the reference to the community, whether these are funded by this FOA or are provided by a key collaborator?

Additional Review Criteria - Project 1: Human Pangenome Reference

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not applicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not applicable.

Additional Review Considerations - Project 1:Human Pangenome Reference

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.

Applications from Foreign Organizations

Not applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Overall Impact - Project 2: Community Outreach and Adoption

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

Scored Review Criteria - Project 2: Community Outreach and Adoption

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

Significance

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

Do the proposed plans for community outreach, training, and feedback solicitation clearly lay out their significance and effectiveness?

Investigator(s)

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

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Is a plan to engage with international stakeholders and partners adequate to ensure the creation, maintenance and dissemination of an equitable resource representative of the world's populations? Do these plans describe how collaborations will foster scientific and intellectual contributions from all partners?

Is there a clear plan for identifying potential partner consortia to serve as early adopters of the pangenome reference? Do these plans target a sufficiently broad sector of the genomics community and adequately describe how these partnerships will operate?

Is there a plan to engage with participant communities underrepresented in resources of human genetic diversity such as indigenous populations and populations from the global south? Do these plans adequately describe how community needs and concerns will be addressed?

Are there adequate plans to conduct outreach with researchers from diverse backgrounds, including those from underrepresented groups in the genomics workforce as well as identify, engage, support, and partner with lower resourced institutions conducting research to promote a diverse community of researchers that contribute to and deliver a widely accessible resource?

Are plans adequate for provision of information about the reference to the research and clinical communities?

Are training, education, and outreach plans well-described? Do they make efficient and creative use of resources (e.g., through online training, social media )? Do they target potential users at different career stages and levels of expertise? Do they address potential misuses of the human pangenome reference?

Are plans adequate for aggregating or indexing useful informatics tools for use of the reference?

Is there a viable plan for gathering information on use of the reference (e.g., via use statistics, metrics, surveys, focus groups ) to understand uses and users of the reference? Does the application describe how this information will be used to improve the reference and its presentation?

Overall, is the plan for research community outreach of adequate quality considering that the human pangenome reference will be an essential and widely used community resource and that the HGRP aims to promote improvements in the reference that may entail significant change?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria - Project 2: Community Outreach and Adoption

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not applicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not applicable.

Additional Review Considerations - Project 2: Community Outreach and Adoption

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.

Applications from Foreign Organizations

Not applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Overall Impact - Project 3: HGRP Logistical Coordinating Center

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

Scored Review Criteria - Project 3: HGRP Logistical Coordinating Center

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

Significance

Does the proposed project address the needs of the research program that it will coordinate? Is the scope of activities proposed for the project appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program?

Investigator(s)

Is the project lead and other personnel well suited to their roles? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing complex, multi-component research? Do the investigators demonstrate significant experience with coordinating collaborative research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach and organizational structure appropriate for the project? Does the applicant have experience overseeing selection and management of subawards, if needed?

Innovation

Does the application propose novel strategies or communications tools for helping to in coordinate the research program the project will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of strategies or communications tools proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research program the project will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are plans adequate for facilitating communication within the program consortium? Do they adequately anticipate needs for meetings, conference calls, taking notes, tracking action items? Is there a plan to improve upon and resolve pain points, bottlenecks, or other impediments to the successful and efficient running of the program that may have been encountered during the first phase of HGRP?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria - Project 3: HGRP Logistical Coordinating Center

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not applicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not applicable.

Additional Review Considerations - Project 3: HGRP Logistical Coordinating Center

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.

Applications from Foreign Organizations

Not applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group 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 NOFO.

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.

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: Grantee 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.

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 condition of receiving the grant, to administer 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. 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 other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this award will be managed as a 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 recipient. Specific tasks and activities may be shared among the recipients; within the consortium and the NHGRI staff as defined below.

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

• 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.
• Ensuring that the data produced as part of this project are released appropriately according to the Data Management and Sharing Plan.
• 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, as needed, to promote synergy and consistency among similar or related projects.
• Ensuring that timelines and goals are met for the Plan for Enhancing Diverse Perspectives (PEDP).
• Collaborating with the Human Pangenome Coordinating Center (CC). Recipients that are part of a consortium will work collaboratively with a CC 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 reci pient receives the appropriate approvals for sharing data between the CC and selected data repositories including The NHGRI Analysis, Visualization, and Informatics Labspace (AnVIL) and other appropriate public databases.
  • Transferring, in a timely manner, detailed (sequence, variant, other genomic, functional, phenotypic, family history, clinical, etc.) and related data and metadata, as appropriate, to the CC using agreed-upon formats and processes, to facilitate dissemination of data more broadly through databases such as AnVIL and other appropriate databases.
  • Sharing the informatics tools through the CC, which will maintain a list of pangenome tools for dissemination to the community.
  • Collaborating with the CC 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) and the SC.
  • Providing reports, summary statistics, and data, as appropriate, in a timely fashion. .
  • Sharing research resources, tools, and data of interest as described in the NOFO and consistent with achieving the goals of the project.
  • Assessing and disseminating data, protocols, consent materials, and methods developed for or derived from the CC within and outside the Consortium.
  • Abiding by common definitions, protocols, and procedures.
  • Attending and participating in SC and other working group meetings and accepting and implementing decisions made by the SC.

NHGRI 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 the 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 manage 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 recipients 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.
• Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium/Network decides to publish, co-authoring manuscripts through their role in scientific program management.

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 individual input and advice to the NHGRI PS/SO about the project. The PS/SO will work with the SC to appoint scientists as ESCs and will determine the duration of service. Activities of individual ESCs could include:

• Participating, as appropriate, in consortium meetings, Steering Committees calls, and the annual recipients' meetings; a subset of ESCs 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 use recommendations from individual ESCs to make project changes, as appropriate.

Areas of Joint Responsibility:

If 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 consortium. This is accomplished by:

• Meeting monthly with the consortium SC 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 ESP recommendations.
• In addition to the PD(s)/PI(s), key co-investigators and pre- and postdoctoral scholars , including those who are members of under-represented groups or those from different but related disciplines, are eligible to attend these meetings. NHGRI encourages these co-investigators and scholars to become involved in key consortium working groups, to lead and report on analyses, etc.

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 maintain an overview of progress and the activities of any working groups that may be formed to implement the consortium, 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 be composed of one representative from each of the grants awarded in the 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.

• The SC will develop its own operating procedures.
• The SC may establish subcommittees to oversee the development and implementation of consortium policies including data releases, publications and standards, etc. Subcommittees 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 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 most 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

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.

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. Awardees will provide updates at least annually on implementation of the PEDP.

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 75.113and 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 75and 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]

Alexander Arguello, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 240-731-3753
Email: [email protected]

Rudy Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: [email protected]

Zephaun Harvey
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7859
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.