Part 1. Overview Information

Key Dates

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

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The National Human Genome Research Institute (NHGRI) will renew the NHGRI Human Genome Reference Program (HGRP). This NOFO seeks applications for the production of High Quality Reference Genomes ( Genomes Center ) as one of three components of the renewed HGRP. The Genomes Center component will lead the prioritization, recruitment, and selection of samples from diverse participants consented for open access data release, and, with those samples, produce 200 very high-quality haplotype-resolved human genome assemblies for inclusion in the human pangenome reference.

The Genomes Center component will also include a team of ethical, legal and social implications scholars who will be embedded in the overall HGRP. This team will be fully integrated with the consortium to help identify and navigate topics raised by the development of a human pangenome resource, including consent, data release and sovereignty, definitions of diversity, and others that may arise over time.

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 t he 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 in the reference genome. 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, this NOFO; 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, see 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 recipients 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).

Research Objectives

Sample selection and prioritization. The Genomes Center will build on the previous HPRC efforts, which are expected to yield about 350 new high quality genome assemblies by the end of the current HGRP program funding period by producing an additional 200 high quality genome assemblies. For the program renewal, the Genomes Center will lead recruitment, selection and prioritization, with final priorities determined at the Steering Committee level within the HGRP.

In the HGRP renewal phase, prioritization of samples must consider several factors. As with the initial phase of the HGRP, samples should be prioritized to improve representation of the pangenome, considering multiple ideas and contexts about how to achieve population genetic diversity (e.g., in terms of the distribution of genetic variation) and representation (e.g., ensuring that participants are from diverse geographic, ethnic or other socially defined categories). In addition, the Genomes Center should prioritize samples that will add to the utility of the pangenome resource for genomics researchers. In many cases, this is likely to overlap with the other goals, but, as the new pangenome reference is adopted, and user needs become better defined, these priorities may diverge. It is anticipated that the sample prioritization criteria will be re-evaluated by the Genomes Center and change over time to accommodate new knowledge or best practices regarding all of these factors.

This effort will use mostly newly acquired samples, though existing samples may be used if they meet the selection priorities. Sufficient samples must be obtained to allow for sequencing of 200 high quality genomes with participant’s consent for full unrestricted ("open") access data release with no research use restrictions within current NIH policy (https://sharing.nih.gov/genomic-data-sharing-policy). Applicants are advised that the 1000 Genomes Project samples should not be considered sufficient to fulfill all the goals of the renewed program due to limitations in representing worldwide genetic diversity, and the need for consents that are better tailored for use in a contemporary pangenome reference.

In addition to these 200 genomes with open sharing and unrestricted use, there may be benefit to also include individuals from indigenous communities or communities outside of the US who may consent to have their genome included in reference genome activities, but choose not to consent for full unrestricted use. The Genomes Center (and the program consortium) may work with samples and sample data from such research participants if the consortium, with NHGRI Program assent, determines that the data from those samples are of high scientific value, not otherwise obtainable, and will support the overall HGRP goals. Rationales may include furthering international collaboration/participation, unique value of the samples to larger consortium goals, or the availability of privacy-preserving methods to make the information usable as part of the larger consortium efforts. These samples should augment the requirement of 200 open access samples, and no more than 5% of the production budget may be spent on such samples.

In general, the Genomes Center should develop a framework and metrics for their sample selection strategy that considers the tradeoffs between all selection criteria, including genetic diversity, population representation, and utility for genomics investigators, along with considerations about data access and factors such as quality and number of assemblies needed (see below). Sample prioritization should be done in concert with the other components of the HGRP, and, where needed, outside consultation

Data production and genome assembly. This NOFO expects production of very high-quality, haplotype-resolved genome assemblies for addition to the pangenome reference, using the best available technologies (e.g., a mix of short-read, long-read, synthetic long-read, optical mapping). The appropriate metrics for these high-quality genomes, and the ability to consistently produce them, were established during the initial phase of the HGRP. However, continued optimization of methods and metrics will still be important, given ongoing changes in technology and cost of some data types, and the new emphasis on utility for the community. Consideration of metrics will also become more important should the HGRP seek to work with data from samples sequenced outside of the consortium, e.g., as part of international collaborations.

This NOFO asks the Genomes Center to produce 200 high-quality, and haplotype-resolved human genome sequence assemblies for open access over 5 years, with the option to add additional samples of high value that may require controlled data access (see above).

The total number of genomes to be produced, and sequencing metrics to be used, will be evaluated before funding starts and periodically over time, and may be adjusted by NHGRI in consultation with the consortium Steering Committee, based on new knowledge, cost decreases, availability of co-funding, or other factors.

The data production and assembly objective also includes prospects for sequencing cost reduction (while maintaining or improving quality), consideration of how quality of the products will be assessed in an ongoing way, and how the data and assemblies will be made available, both to other HGRP program components, and to the wider community.

Applicants for this NOFO may propose plans for using up to 10% of the data production budget for producing other types of data that can be obtained through sequencing, for example RNA sequencing, as long as the plans are justified on the basis of how such data will improve the quality and usability of the pangenome reference, and how the information will be integrated with the pangenome.

Embedded Ethical, Legal, and Social Implications (ELSI) Research component. Experience from the initial phase of the HGRP indicates that a fully integrated ELSI research team is needed to guide the consortium through numerous challenges that if not addressed would hinder the development of the resource, make the resource less useful, or indirectly lead to health or research disparities. The main purpose of the embedded ELSI research component is to ensure that the HGRP anticipates and addresses key challenges that are inseparable from the scientific goals of the program. In this renewal period, the Embedded ELSI Research Component is expected to go beyond identification of key issues and challenges to the production of research that can move the HGRP, and the broader field forward. Accordingly, the ELSI research team is expected to use diverse research methodologies to identify, assess and develop possible approaches to key ELSI challenges faced by the HGRP.

ELSI challenges may include issues such as determining adequate consent for creation of a human pangenome resource and associated resources such as induced pluripotent stem cell lines, etc. Other topics that have been raised include data sovereignty, considerations about diversity, appropriate population descriptors, and equity, i.e., that the resource is developed in a way that ameliorates, rather than propagates, health disparities. Additional issues posed by the use and adoption of a pangenome reference in different settings or by new user communities should be anticipated early in the project in order to guide program decisions. Examples could include the regulatory implications of the use of the pangenome in the clinic or legal requirements related to international collaborators.

The ELSI research component will also incorporate foundational ELSI principles and relevant literature into key program decisions such as defining diversity within the HRPC and how to prioritize samples. The ELSI research team should work collaboratively within the consortium to develop frameworks for the consideration of equity within the HGRP, including the establishment of appropriate metrics to assess the progress of the HGRP towards the high-level goal of ameliorating health disparities. The ELSI research component should also work with other consortium members to produce recommendations for the use of population descriptors such as race, ethnicity, genetic distance, etc. considering existing scholarship, consensus recommendations from relevant organizations and groups, and the specific research context of the HGRP.

The ELSI research team should also collaborate with other HQRC and HGRP colleagues on research participant engagement and community engagement more broadly, as appropriate. Such engagement activities may include outreach to research participants or communities from groups that have not previously participated in pangenome projects, such as international partners and/or indigenous communities.

It is expected that work on the human pangenome will continue to raise new issues over time. The ELSI research component will be charged with helping to identify and anticipate new issues throughout the course of the HGRP and address such issues in a timely and collaborative manner.

NHGRI does not intend the HGRP program funding to be used for extensive independent ELSI research that is unrelated to the specific needs and challenges posed by the HGRP. The Embedded ELSI Research Component should be tightly linked to and deeply informed by the key goals and foundational principles of the HGRP.

Even though the primary funding for the ELSI research component is provided through the Genomes Center, it must be fully integrated into the consortium as a whole, for example through participation in working groups, the steering committee, and having an equal role in decision-making for the project. One of the Multiple PI’s (MPI) on this application must be an ELSI investigator.

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, 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 Genomes Center must reflect this, including how the ELSI component will be integrated, and how data and assemblies will be made available to the HGRP and the community.

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 ESC members 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):

• Samples (e.g., cell lines) used for sequencing through an established repository
• 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.
• Products, recommendations, tools and data from the embedded ELSI Research Component

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). Data should be released through the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL), and other resources as appropriate to enhance dissemination. The Genomes Center will work collaboratively with the other HGRP recipients to ensure compliance with the NIH data sharing policies (sharing.nih.gov), and NHGRI’s expectations which are summarized at (www.genome.gov/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 data sharing plan with the prospective recipient. . The final negotiated version of the data sharing plan 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 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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

This is a limited competition RFA. Only recipient organizations funded under RFA-HG-19-002 are eligible to apply.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Adam L. Felsenfeld Ph.D.
Telephone: 301-435-5539
Email: [email protected]

Page Limitations

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

For this specific NOFO, the Research Strategy section is limited to 30 pages.

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

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 in research including those from under-represented groups in research

SF424(R&R) Senior/Key Person Profile

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

Without duplicating information contained the biosketches, describe the investigator's experience successfully leading and coordinating efforts of comparable size and complexity.

R&R Budget

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

Investigator effort: Effective management of this center requires a significant commitment by Program Director(s)/Principal Investigator(s). A PD/PI is expected to commit a minimum of 2 person months annually. An investigator with demonstrated ELSI experience must be included as part of the leadership team. If using an MPI model, the aggregate level of effort required of all MPI’s combined is a minimum of 3 person months.

Embedded ELSI: The budget for the embedded ELSI component should be approximately 15-20% of the direct costs of the Genomes Center.

High-value samples without consent for open and unrestricted data release: If proposed, the budget for sequencing any samples from participants who provided consent that included data use or availability restrictions (i.e., that are not open and unrestricted) must not exceed 5% of the direct cost budget for data production.

Data beyond DNA sequence: If proposed, the budget for producing data beyond DNA sequencing (e.g. RNA sequencing) for improving the quality and utility of the reference is limited to 10% of the direct costs for data production.

Annual meetings, outreach and adoption: Budgets should include costs required for active participation in virtual and in-person meetings of the HGRP, including annual consortium meetings and participation in outreach and adoption efforts, which may include workshops.

PEDP Implementation: 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 .

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

In general, for each element of the Research Plan listed below (i.e, Sample selection, Data production, Embedded ELSI, Center management, and Resource sharing) , applicants should provide:

• A detailed plan for how the applicant proposes to meet the element's objectives, both independently and in collaboration with the other awardees of the HGRP
• Benchmarks for success
• Proposed timelines and milestones for the whole project period
• A description of anticipated key issues and challenges

Applicants are encouraged to include in the application additional topics or features that may improve the quality and utility of the human pangenome reference.

Additional information applicants should provide for specific components is described below.

Sample selection and prioritization

For all samples: Applicants should provide plans for how they will select and prioritize all samples for addition to the human pangenome reference. Applicants should justify the value of additional samples in terms of improving the current human pangenome reference ensuring that it meaningfully represents genetic variation and worldwide populations, and with a new emphasis on improving utility for and adoption of the pangenome reference by the community of genomics researchers and clinicians.

As part of these plans, applicants should propose how to evaluate over the course of the award whether additional new samples are needed to meet the HGRC goals. The sample selection and prioritization should include proposed plans and methods to predict, and then later assess, the added value of new samples.

Applicants should identify and consider tradeoffs, e.g. between quality, quantity, diversity, usability, and functionality; whether and how prioritization of new human assemblies may tend to help some sectors of the community vs others (e.g., clinical vs basic researchers).

Applicants should discuss quality standards for samples, including eg. minimizing the number of passages and sample QC. Applicants should discuss how samples will be distributed or otherwise provided for potential community use.

Applicants should describe how input from the other program components, including the embedded ELSI component, tools, and adoption projects could be integrated into this framework.

Applicants should discuss their consideration of population descriptors in the context of this project, including any differences between the context of individual samples/genomes, vs. describing proportional contributions to the resource.

Working with the Coordinating Center, applicants may consider including data from samples that have already been sequenced to HGRP quality standards and that otherwise meet all prioritization criteria, including consent.

For all samples that will have consent for open data sharing and unrestricted use: Applicants should describe how they will obtain sufficient samples to meet the required metric of 200 reference quality genomes from research participants who consented for open access. Applicants may propose to collect more than 200 samples, for example to account for quality control failures, or for being sub-optimal for addition to the pangenome according to evolving criteria. Applicants should provide a timeline for acquiring the samples that they need.

The application should discuss how new research participants will be recruited, and how they will be consented. Applicants should describe what an appropriate consent for the HGRP should include for participants consenting for unrestricted data sharing with full unrestricted ("open") access data release with no research use restrictions within current NIH GDS policy. Applicants should discuss any needed participant community engagement.

The application should describe plans to use samples other than the 1000G samples, including descriptions of consents that will be better tailored for use in a contemporary pangenome reference.

For samples without open consent but with unique value: This NOFO allows applicants to propose additional samples to augment the 200 described above. The application should describe any plans or frameworks proposed for samples that will be potential exceptions to the requirement for full unrestricted access. This should include justification based on the value and uniqueness of the samples, even considering that the data may not be fully open or unrestricted. In this context, applicants should discuss outreach and engagement with the relevant communities, data sovereignty requirements, dissemination of knowledge and methods, etc For these samples, the application must describe how the data will be disseminated, including data repositories, ability to access, use restrictions, development of computational means to protect privacy, etc.

Data production and genome assembly

Applicants should describe their plans for producing 200 open access reference quality haplotype-resolved human genome assemblies, as well as any additional genomes proposed (see above) for addition to the pangenome reference.

Applicants should propose and justify quality metrics for defining what constitutes a very high quality, assembly for the purposes of the HGRP. They should then discuss the strategy for producing sequence data that meet those metrics, balancing costs/funds available and use of best available technologies (e.g. a mix of short-read, long-read, synthetic long-read, optical mapping, etc.). They should describe how they will work with the HGRP governance as a whole to evaluate metrics in an ongoing way, for example to match quality to utility, to respond to changes in technology or cost, etc.

Applicants should describe informatics pipelines that will be used and discuss any internal or external validations that will be done. Applicants should describe plans for making their informatics pipelines, methods, and protocols available as an open access, non-proprietary resource. See the Resource Sharing Plan section below; resource sharing plans will be considered in the priority score.

Applicants should propose a plan and metrics for variant calling for the range of different variant types. This should include plans for harmonizing efforts with other program components that will also be calling genomic variants in order to produce a high-quality product in the context of this program.

Applicants should discuss how the data, including sequence, assemblies, variants, and relevant metadata will be made available. See the Resource Sharing Plan section below; resource sharing plans and data management plans will be considered in the priority score.

Applicants should include information on estimated costs (labor, reagents, amortized equipment, not including indirect costs or methods development costs) per high-quality genome and discuss tradeoffs in the context of how they justify the quality of the proposed project. Applicants should also discuss prospects for cost reduction over the course of the project.

In addition to prospects for cost reduction, applicants should discuss prospects for improved technology platforms to be used, plans for assessing sequencing technologies in the context of the HGRP, and required quality over the course of the project.

Products beyond DNA sequence: Applicants may propose plans for using up to 10% of the data production budget for generating other types of information that can be efficiently obtained through sequencing beyond high quality genomes, for example RNA sequencing, as long as the plans are justified on the basis of how such data will improve the quality and usability of the pangenome reference, and how the information will be integrated with the pangenome. If this is proposed, the application should also include a description of the methods, strategy, protocols, metrics, QC, and informatics pipelines that will be used, as well as how these data will be made available.

Embedded Ethical, Legal, and Social Implications (ELSI) Research component

Applicants should describe what they see as the major ELSI issues that the HGRP, and larger international HPRC, should anticipate and address, in an ongoing way, over the five year period of the program. This description should highlight the significance of the ELSI issues, with a focus on key challenges that are unique to or inseparable from the overall scientific goals of the HGRP. Applicants should address how they will work within the program to address these challenges, including a description of the methodologies and approaches that will be used. Applicants should include detailed strategies for how they will regularly identify and anticipate new or emerging issues throughout the course of the HGRP and how such issues will be addressed.

In addition, applicants should describe detailed strategies for how they will address established challenges that are foundational to the design and purpose of the HGRP. Key examples include, but are not limited to, plans for establishing standards for adequate consent for a human pangenome resource and associated products and strategies for research participant engagement, particularly for groups that have not previously participated in pangenome projects. Applicants should describe in detail how they will contribute to discussions and produce scholarship related to data availability, access and sovereignty, particularly with communities or groups who may be willing to consent to HGRP participation only under a more restricted data sharing model. Applicants should also describe potential challenges posed by the use and adoption of a pangenome reference in different settings or by new user communities and how they will identify, address and collaborate to support the goals of the HGRC.

Applicants should describe detailed strategies, including specified methods and approaches, for how they will incorporate foundational ELSI principles and relevant literature into key program decisions and frameworks for the consortium. Examples of such key decisions include, but are not limited to, how to define diversity within the HGRC consortium, how to prioritize samples, the use of population descriptors, and appropriate metrics and frameworks for considering equity within the consortium.

Applicants should explain how the roles of the embedded investigators, their range of expertise, and any past involvement with pangenome-related ELSI work will be likely to lead to productive integration into the HGRP and overall success in producing a human pangenome reference.

In describing the embedded ELSI Research Component, applicants may refer to strategies, expertise and approaches detailed in other portions of the application or key ELSI issues raised or referenced by other Consortium components. Applicants should address how the ELSI component will be fully embedded in the consortium as a whole, for example participating in working groups, the steering committee, and having an equal role in decision-making for the project. Applicants should explain how this integration will be achieved. One of the MPI’s on the application must be an ELSI investigator.

Center management and integration with the consortium

Applicants should provide an overview of the management and structure of the Genomes Center, explaining how they will ensure the efficient planning, initiation, implementation, and timely completion of all activities and day-to-day oversight of the activities within this one component of the larger HGRP, with clear mechanisms for decision-making. Applicants should provide timelines and milestones.

Applicants should describe how their work will be integrated with that of the companion program components (Coordinating Center, Tools Projects) to ensure that the higher-level goals of the HGRP towards producing a pangenome reference resource are realized. The governance and project management structure and plans of the Genomes Center must reflect this, including e.g.:

• How the ELSI component will be integrated
• Overall data flow; how data and assemblies will be made available within the HGRP
• How the products of the research will be made available

Applicants should explain how they will work with existing entities that provide, improve, annotate, etc. genome references. This includes coordination with NCBI and with other national and international groups that contribute to the genome reference that may not be funded by this NIH program but are essential to the utility of the reference.

Because the major new goal of the HGRP renewal is to ensure that the human pangenome is widely adopted, applicants should describe how the Genomes Center specifically will engage with outside consortia, for example those using the data (for outreach), and those developing improved sequencing and assembly methods.

Applicants are strongly encouraged to contact NIH Staff (see Agency Contacts) to discuss the alignment of their proposed work with the goals of this NOFO.

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.
• How samples (e.g. cell lines) used for sequencing will be made available e.g. through an established repository.
• How protocols and quality standards that were developed for producing high-quality genome assemblies will be made available.
• How products, recommendations, tools and data from the embedded ELSI Research Component will be made available.

After initial review, NHGRI program staff will conduct an additional administrative review of any plans for sharing data and 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.

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. At a minimum this plan should address:
  • Samples (e.g., cell lines) used for sequencing through an established repository
  • 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.
  • Products, recommendations, tools and data from the embedded ELSI Research Component

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

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Post Submission Materials

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

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

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

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

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

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

2. Review and Selection Process

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

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

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

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• 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: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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

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

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. 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.html and https://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.

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

The PS/SO will have the following substantial involvement:

• Serving as a liaison, helping to coordinate activities among and for the recipients, including acting as a liaison to the NHGRI and as an information resource for the recipients about genome research activities. The PS/SO will also coordinate the efforts of the recipient(s) with other groups conducting similar studies.
• Reporting periodically on the progress of the recipients to the NHGRI Director and to the National Advisory Council for Human Genome Research.
• Assisting recipient(s) in the development, if needed, of policies for dealing with situations that require coordinated action.
• Providing advice on the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed in the course of the award to the scientific community.
• Being responsible for the normal scientific and programmatic stewardship of the award, including assessments of how well the recipient has met any milestones required for each year of funding.
• Curtailing, withholding or reducing support for any recipient that fails to make satisfactory progress toward the work scope that NHGRI approved, has ethical or conflict of interest issues, or fails to comply with the Terms and Conditions of Award.
• Involving NIH or NHGRI staff who may assist the recipient(s) as designated by the PS/SO.
• 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 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 durations 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 ESC’s 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 trainees, 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 trainees 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. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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

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

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

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

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

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

Lisa Oken National Human Genome Research Institute (NHGRI)
Telephone: 301.594.5250
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.