It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The National Human Genome Research Institute (NHGRI) seeks to fund the production of High Quality Human Reference Genomes (HQRG) as a component of the NHGRI Human Genome Reference Program (HGRP). One aim of the HGRP is to develop a genome reference that is representative of human population genetic diversity. To help achieve this goal, this HQRG initiative is expected to establish metrics for high quality-genome assemblies; collaborate with other HGRC awardees on sample selection and prioritization; produce about 350 high quality, and ideally, haplotype-resolved human genomes, using diverse samples consented for full data release; and provide capacity to help resolve error reports received by the HGRC.

This and related FOAs will replace and update NHGRI's current contributions to the Genome Reference Consortium https://www.ncbi.nlm.nih.gov/

The National Human Genome Research Institute will issue multiple FOAs to fund a Human Genome Reference Program (HGRP) that is intended to replace and update its current commitment to activities now undertaken by the Genome Reference Consortium (GRC). The Genome Reference Consortium provides a resource used by essentially all researchers who align and read-map experimental or patient genome sequence data. It also serves as a consensus coordinate system for reporting results. The GRC improves the reference, curates and releases updates and new reference builds, develops representations and alignment tools so that the community can use the reference and alternative haplotype information within it, resolves error reports from the community, and performs outreach. The GRC operates as an international consortium, with support provided by NHGRI, as well as the Wellcome Trust and the National Center for Biotechnology Information.

As an outgrowth of the International Human Genome Project, the current human genome reference has sustained and supported genomic research for more than the last decade. However, there is need for improvement in several areas. In considering its commitment to the GRC, NHGRI convened over 65 basic research, clinical, and bioinformatic scientists in a web meeting to discuss "Human Genome Reference Sequence Opportunities". Several issues were raised at this meeting. First, the reference does not adequately represent human population genetic diversity. This will result in suboptimal ability to map short-read genome sequence data to the reference, in a way that is biased to favor the populations already represented in the reference. Second, we need improved approaches for representing variation from multiple individual sequences, in order to fully capture human diversity in a pan-genome , improve how that information is represented, and to ease computation and downstream use. Third, the community of users of the reference continues to expand and diversify, meaning that new informatics tools will need to be developed to make the reference easily usable for multiple communities.

NHGRI is proposing the HGRP to re-organize and re-focus its contribution to the genome reference to enable an improved human genome reference for the community, and to foster its long-term sustainability and improvement.

This FOA covers one component of this HGRP overall activity, the production of High Quality Human Reference Genomes (HQRG). The FOA will be released in conjunction with at least two other FOAs, one for a Human Genome Reference Center (HGRC), and one for Research and Development for Genome Reference Representations. NHGRI intends to also fund related activities in Research and Development for Comprehensive Genome Sequencing and Informatics Tools for the Pan-genome. Successful applicants for this and related FOA are expected to collaborate with each other, and with other international resources and efforts related to genomic references. NHGRI seeks competitive applications from all eligible institutions, whether currently supported for human genome reference activities or not.

This FOA for the HQRG seeks applications for efforts that aim to produce about 350 high-quality, and ideally, haplotype-resolved human genomes. Sample selection and prioritization will be done collaboratively at the Steering Committee level within the HGRC. It is anticipated that this effort will initially use existing samples with sufficient diversity and with consent for full unrestricted ("open") access data release with no research use restrictions within current NIH policy (http://gds.nih.gov/). The HGRC, along with the larger GRC, will evaluate whether additional samples are needed to obtain appropriate haplotype diversity to meet the HGRC goal of capturing as much human diversity as possible in a pan-genome . This may require the HQRG to coordinate the consent and collection of new samples, which should be consented for unrestricted access data release.

This FOA expects production of high-quality genome assemblies at levels needed for the human reference, 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.). The appropriate metrics for these high-quality genomes, and the best way to add diversity, are still partly open scientific questions. For example, as an ideal goal, it may be that very high-quality assemblies should fully resolve haplotypes at chromosome scale. However, this may not yet be feasible, and in the context of the pan-genome it may not formally be necessary, yet clearly a high level of haplotype resolution is desirable. We anticipate that program metrics and priorities will be established through discussion within the HGRP as a whole before significant data production begins. Moreover, sequencing technologies, cost, required quality, and added value of new genomes will be assessed by the program over the course of the project, as these considerations are expected to change over time.

The HQRG may also provide capacity when whole genome sequencing is required to help resolve error reports received by the HGRC. The HGRC may be responsible for the computational approaches and targeted sequencing production for error reports. A final protocol for addressing error correction will be established through discussion within the HGRP as a whole.

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

Consistent with achieving the goals of this program, NIH expects that appropriate data and meta-data for the high-quality human genomes, and any sequencing performed to resolve error reports will be widely shared with the scientific community. Awardees are expected to comply with the NHGRI Genomic Data Sharing Policy (https://gds.nih.gov/). Resources such as study protocols, sequencing meta-data, sequencing metrics, and bioinformatic tools are expected to be made available. Collaborative environments, such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) (https://www.genome.gov/27569268/the-nhgri-analysis-visualization-and-informatics-labspace-anvil/), may be considered for data sharing.

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

NHGRI will conduct a webinar to answer questions from prospective applicants. Webinar information and FAQs are available at https://www.genome.gov/27572476/human-genome-reference-program-webinar/

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

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

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

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)
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• 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.
• o 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

Only one application per institution (normally defined by having a unique DUNS number or NIH IPF number is allowed).

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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 NOT-OD-11-101).

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement 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.

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:

Dr. Adam Felsenfeld
Telephone: 301-480-2296
Email: [email protected]

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

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

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

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

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

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

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

Costs associated with sequencing should be reported in a way that is consistent with current NHGRI cost reporting. Costs should be readily relatable to the discussion in the research plan about the number and quality of the genome assemblies.

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

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

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

Research Strategy:

Applicants should describe their plans for producing about 350 reference quality haplotype-resolved human genome assemblies. The applicant should state and justify a specific number they can produce given the expected funding levels, while recognizing that the final number needed to achieve the program goals is likely to be an important topic for the HGRP as a whole.

Applicants should propose and justify quality metrics for defining what constitutes a very high quality, ideally haplotype-resolved, genome assembly for the purposes of the human Genome Reference Program. They should then propose a strategy for achieving 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 establish final metrics before significant data production begins. Applicants should describe informatics pipelines that will be used for assembly and discuss any internal or external validations that will be done.

Applicants should propose a plan and metrics for variant calling for the range of different variant types. It is highly likely that another program component, the HGRC, will also be calling genomic variants in order to produce a high-quality product in the context of this program. These two plans will be harmonized once the consortium is formed.

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 plans for assessing sequencing technologies, required quality, and added value of new genomes over the course of the project.

Applicants should propose an initial set of samples that can be sequenced using the capacity proposed for at least the first year the project. These samples should have sufficient ancestral genetic diversity, and consent for full unrestricted ("open") access data release with no research use restrictions within current NIH policy (http://gds.nih.gov/). Applicants must justify the diversity of these initial samples with respect to populations of origin in the context of improving the current human genome reference sequence and its uses in both research and clinical contexts. Applicants should demonstrate that they understand that final decisions about these priorities for sample selection will be made by the HGRP as a whole.

Applicants should propose a plan for working within the HGRP to evaluate whether additional new samples are needed to obtain appropriate haplotype diversity to meet the HGRC goal of fully capturing human diversity in a pan-genome . This should include a description of methods that could be used for determining whether new samples are needed, the number of new samples, and the population origin of new samples.

Applicants should describe expertise and resources for the collection of new samples, including for consenting individuals from diverse populations for unrestricted data sharing.

Applicants should address their sequencing capacity for resolving error reports received by the HGRC that require whole genome sequencing, including technologies, costs, and turn-around time.

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, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Applications are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111.

The Resource Sharing Plan is expected to also include:

• For this FOA, applicants are expected to address how they will work with existing community resources that archive or improve genome references. This includes coordination with NCBI and with other national and international groups that contribute to the genome reference.
• Applicants should also describe how they will share appropriate sequencing metadata, with a focus on existing or emerging standards for FAIR (findable, accessible, interoperable and reusable) genomic data.
• Applicants are expected to address how sequence data, variant, assembly and other data will be shared in a timely manner consistent with NIH policy. For this specific FOA, this should include plans for making the data available with broad sharing and unrestricted-access of data (i.e. openly accessible data repositories). Applicants should discuss how samples are consented for such use.
• Applicants should address how any research tools (including informatics analysis or data processing tools) and new methods developed under this award will be made available. For this FOA tools, methods and software should be well-documented and, where applicable, made available via version-controlled public repositories.

Appendix:

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

When involving NIH-defined human subjects research, clinical research, and/or 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.

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

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

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

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.

This initiative is not subject to intergovernmental review.

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.

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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review 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 FOA number and title, PD/PI name, and title of the application.

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.

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.

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

Specific to this RFA:

Is it likely that the proposed work will add significantly to the value of the Human Genome Reference?

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

Specific to this RFA:

Do the investigators have experience in sequencing, assembling and making available to the community high-quality genome sequence data? Do they have the experience with specialized technologies and approaches needed to generate haplotype-resolved assemblies? Do the PD(s)/PIs have experience with consenting and collecting new samples? Do the PD(s)/PI(s) have experience in working collaboratively in consortia or other coordinated projects similar in scale and complexity to the GRC?

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?

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?

Specific to this RFA:

Are the quality and number of genome assemblies clearly specified and justified? Are quality metrics for a haplotype-resolved genome clearly stated and justified, and thoughtfully related to the needs for a high-quality human reference? Is the data production plan clear and sound, and will it achieve these metrics? Does the application describe an adequate informatics pipeline for data processing, genome assembly, and variant calling, with appropriate internal and external validations? Do applicants have a reasonable proposal for how they will finalize metrics and set priorities for adding new genomes, within the context of the HGRP governance?

Does the application make reasonable tradeoffs between cost and quality in the context of how they justify the approach for the proposed project? Are prospects described for cost reduction over the time of the award? Is there a reasonable proposal for assessing and re-evaluating the approach over the course of the project?

Are the number and population diversity of the initial set of samples justified in the context of improving the human genome reference? Do applicants have a reasonable proposal for how they will evaluate the need for new samples, and for determining what samples are appropriate if new samples are needed?

Does the application propose adequate capacity and plans for resolving error reports forwarded by the HGRC in a timely manner?

Does the overall plan take into account the flexibility requested in this FOA for working with other HGRP components in determining final decisions on some key program features (e.g., sample prioritization, assembly quality metrics)?

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?

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.

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.

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.

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.

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.

Not Applicable.

Not Applicable.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS). Reviewers will comment on whether the samples identified are likely to be consented in a way that allows unrestricted sharing of the sequence data and incorporation into community resources including genome references. They will also comment on whether the plans are appropriate for making genomic data FAIR, and appropriate for making software/methods/tools publicly available.

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.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Human Genome Research Institute, 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:

• 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.
• Will receive a written critique.

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

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 FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing policies as appropriate, including consent of human samples that will allow unrestricted access, broad research use, and incorporation into community resources.
• Ability to work effectively as part of the HGRP research consortium, along with other groups that contribute to the human genome reference.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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

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

• Developing scientific plans.
• Meeting the goals and objectives, as well as timelines and milestones set out in the funded application or amended as approved by NHGRI.
• Interacting effectively with the Human Genome Reference Program components.
• Accommodating any necessary changes to improve the efficiency of operations and services and to decrease costs.
• Providing interim reports or information requested by NHGRI staff.
• Addressing and implementing the guidance and recommendations of the External Scientific Panel (ESP), as described below.
• Participating in or leading working groups that focus on topics or activities that affect the value, quality, and efficiency of the operations and services provided by the HQRG.
• Participating effectively with collaborators that work to produce genome references, develop related standards, develop priorities for addition of new genomes, provide variation resources, etc.
• Assisting in the development of policies for dealing with situations that require coordinated action.
• Ensuring that the data underlying the human reference are available to the community in a manner consistent with policies, and according to best practices for handling the data.
• Adopting new solutions and technologies to ensure appropriate use of data underlying the reference.
• Data and software transition. At the end of the award, or if a new recipient has been selected prior to the end of the award, the awardee will work with NHGRI staff and the new award recipient to transition any data, product (reference) and software to the new service, or to the Government.
• Maintaining necessary regulatory and policy compliances related to data access and data security for both unrestricted and controlled access data (if applicable), including any NIH-designated best practices for genomic data sharing.
• Ensuring that the data and related tools and resources developed as part of the HGRP are made publicly available according to NHGRI and the NIH policies.
• Agreeing and accepting close coordination, cooperation, and participation of NHGRI staff in those aspects of scientific and technical management of the service as described under "NIH Program Staff Responsibilities."
• Agreeing to be subject to Government rights of access consistent with current DHHS, PHS, and NIH policies
• Data/software ownership and transition to another grantee:
• A fundamental objective of this cooperative agreement is to ensure that the valuable data, products, and resources provided by the HGRP remain available without interruption to the research community if awardee withdraws or otherwise can no longer manage the resource or the award is terminated by the NIH.
• Consistent with 45 C.F.R. 75.322, the awardee will own the data generated and software developed by the awardee, and it will be able to continue to use these data and software upon expiration or termination of the award. NIH will have unrestricted cost-free access and use of the data, resource and software generated by the awardee, including the right to transfer said data and/or software to other NIH-funded and/or managed resource projects, at the NIH's sole reasonable discretion upon termination or expiration of this cooperative agreement.
• Ownership of the data and software that may be hosted (but not created) by the HGRP remains with the data and software providers.
• Open Source Technology: Capabilities and software built as part of the NHGRI HGRP must be delivered under an open source model. Organizations may propose to use proprietary platforms, so long as the requirements for data transparency and interoperability are maintained.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• Participating with the HGRP-SC and all other relevant working groups in the group process of setting scientific, administrative and technical priorities, facilitating consensus around program policies and certain technical decisions (including metrics for sequence assembly quality and priorities for sample selection and adding new assemblies to the reference consortium) and deciding optimal approaches and protocol designs, and contributing to the adjustment to protocols or approaches as warranted.
• Serving as a liaison, helping to coordinate activities among and for the awardee(s), including acting as a liaison to the NIH, and as an information resource for the awardee(s) about scientific, administrative, and technical activities.
• Assist in coordinating the efforts of the resource with other groups conducting similar efforts at the NIH and worldwide.
• Periodically reporting on the progress of the program to NHGRI Division Directors, the NHGRI Director, and to the National Advisory Council for Human Genome Research.
• Serving as a liaison between the HGRP and the ESP.
• Serving as a liaison between the HGRP and other federal agencies.
• Providing advice in the management and technical performance of the award.
• Participating in data analyses, interpretations where warranted.
• The Program Official may withhold or reduce support from any awardee that fails to achieve its goals or comply with the Terms and Conditions of Award.
• Other NHGRI staff may assist the awardee(s) as designated by the Program Official.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Participation in the Steering Committee. A Steering Committee (or similar coordinating unit for the program) will serve as the main governing board of the HGRP. The Steering Committee membership will include the NHGRI Project Scientist(s) and the P.I. of each awarded cooperative agreement. Additional members may be added by action of the Steering Committee. Other NIH or government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. Each full member (limited to one person per award center, in the case of multiple PI's per center) will have one vote, except for NHGRI Project Scientist(s) who will have one collective vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

To address particular issues, the Steering Committee may establish Working Groups as needed, which will include representatives from the program, the NIH, and possibly other experts.

The Steering Committee will:

• Discuss progress in meeting the objectives of the HGRP;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the HGRP;
• Serve as a venue for coordination on determining the metrics for reference quality genomes sequenced as part of the HGRP;
• Serve as a venue for coordination on determining new sample selection for the HGRP;
• Set agendas for in person meetings of the Steering Committee and the ESP.
• Interact with other relevant NHGRI, NIH and international activities, as needed, to promote synergy and consistency among similar projects.
• Work with and provide information to the ESP.
• Attend in person meetings once a year with the ESP.

An External Scientific Panel (ESP) will be established by NHGRI and will be responsible for reviewing and evaluating the progress of members of the HGRP toward meeting their individual and collective goals. The ESP will be composed of three to five senior scientists with relevant expertise who are not PIs of a cooperative agreement involved in the HGRP. The membership of the ESP may be enlarged permanently, or on an ad hoc basis, as needed. The ESP will meet at least once a year. During part of this meeting there will be a joint meeting with the Steering Committee to allow the ESP members to interact directly with the awardees. The ESP will make recommendations regarding progress of the HGRP and present advice about changes, if any, which may be necessary.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened. It will have three members: a designee of the Steering Committee 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 individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee'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.

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. 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 Appendix XII to 45 CFR Part 75, 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 Award Term and Conditions for Recipient Integrity and Performance Matters.

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: http://grants.nih.gov/support/ (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: 301-945-7573

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

Dr. Adam Felsenfeld

National Human Genome Research Institute (NHGRI)
Telephone: 301-480-2296
Email: [email protected]

Rudy Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8739
Email: [email protected]

Deanna Ingersoll
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: [email protected]

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.