EXPIRED
National Institutes of Health (NIH)
See Section III. 3. Additional Information on Eligibility.
The purpose of this Notice of Funding Opportunity Announcement (NOFO) is to solicit applications for the Coordinating Center (CC) of the ML/AI Tools to Advance Genomic Translational Research (MAGen) Consortium which will include the MAGen CC and the MAGen Sites funded by the companion NOFO (RFA-HG-24-004). The MAGen Consortium is being established to explore the feasibility of developing Machine Learning (ML) and Artificial Intelligence (AI) tools that can enhance the accuracy and precision of predicting how individuals with pathogenic genetic variants manifest disease. The CC will be responsible for implementing approaches to bring diverse teams together to enable synergistic and collaborative team science across the Consortium. Specifically, the CC will be responsible for technical, scientific, and administrative coordination activities to support the Consortium research activities including development of Consortium wide plans, coordinated ELSI-informed ML/AI tool development and cross validation, and dissemination of the developed resources.
The MAGen Consortium will collaboratively identify both genomic and non-genomic factors influencing disease development in individuals carrying pathogenic genetic variants. The ML/AI tools will leverage existing multimodal genomic and non-genomic data and will be cross validated in genomic translational research settings to ensure the robustness and generalizability of the tools for translational purposes. In addition, the Consortium will explore the ethical, legal, and social implications (ELSI) of integrating ML/AI tools into genomic medicine through the establishment of a framework for ELSI studies and through implementation of ELSI research projects.
June 26, 2024.
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
July 26, 2024 | Not Applicable | Not Applicable | November 2024 | January 2025 | April 2025 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late applications will be accepted for this Notice of Funding Opportunity (NOFO).
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Background
Genomic medicine is being increasingly used in patient care. The utility of genomic sequencing in the practice of genomic medicine has been greatly enhanced by the categorization and annotation of pathogenic genetic variants by the American College of Medical Genetics and Genomics (ACMG). However, translational research to advance our understanding of genomic and non-genomic factors that contribute to penetrance, expressivity, and pleiotropy of variants categorized to be pathogenic or likely-pathogenic is needed for more precise and effective practice of genomic medicine. The need for increased research to develop tools to translate genomic research findings into clinical applications has been highlighted by NHGRI-convened workshops (Genomic Medicine XIII, NHGRI Machine Learning in Genomics Workshop: Tools, Resources, Clinical Applications, and Ethics).
Machine Learning (ML) and Artificial Intelligence (AI) have been used for pattern discovery and classification for several decades. Recent advances in computational resources have increased the ability of ML/AI tools to learn and discover previously unrecognized patterns from large, complex multimodal datasets. ML/AI techniques have successfully identified novel patterns in non-genomic clinical datasets, receiving FDA approval for ML/AI-enabled medical devices in fields such as radiology, cardiology, and various other disciplines of medicine.
The potential for using novel ML/AI approaches in translational genomics is facilitated by the vast amounts of multimodal data that have become increasingly available through advances in standards and policies that encourage the sharing of data in a findable, accessible, interoperable, and reusable (FAIR) manner. Utilizing FAIR multimodal data along with rich biological annotations in knowledgebases and literature to train ML/AI models could potentially improve our understanding of the impact of genomic and non-genomic contributors to disease. Furthermore, the capability of such tools to learn from new data and knowledge, complemented by rapidly evolving ML/AI methods, has the potential to increase their future applicability in genomic medicine.
Maximizing the potential of ML/AI requires thoughtful attention to the ethical, legal, and social implications (ELSI) of its use in genomic medicine and healthcare more broadly. Several areas of concern have been raised related to the use and implementation of ML/AI in healthcare. These include biases in data and algorithms leading to misdiagnosis, ambiguities in accountability for misuse of the data and tools, unintended loss of patient privacy and confidentiality, lack of adequate regulatory oversight and monitoring, legal ambiguities around intellectual property rights, overreliance on ML/AI tools in decision making, challenges in patient-provider communication, lack of patient and provider confidence in ML/AI, and furthering of racial or ethnic health disparities. Conducting ELSI research to anticipate and address these and other ELSI issues during the development of ML/AI tools can help improve scientific rigor, reduce harm, and realize the potential for benefit across diverse populations.
For the purposes of this NOFO, the following definitions/descriptions are used:
Research Objectives, Scope, and Approach
The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications for the ML/AI Tools to Advance Genomic Translational Research (MAGen) Consortium Coordinating Center. The MAGen CC will provide technical, scientific, and administrative coordination to support the Consortium research activities including development of Consortium wide plans, coordinated ELSI-informed ML/AI tool development and cross validation, and dissemination of the developed resources. The MAGen CC will work closely with the MAGen Sites funded by the companion NOFO to explore the feasibility of developing Machine Learning (ML) and Artificial Intelligence (AI) tools that can enhance the accuracy and precision of predicting how individuals with pathogenic genetic variants manifest disease.
The MAGen Consortium will collaboratively identify both genomic and non-genomic factors influencing disease development in individuals carrying pathogenic genetic variants. The ML/AI tools will leverage existing multimodal genomic and non-genomic data and will be cross validated in genomic translational research settings to ensure the robustness and generalizability of the tools for translational purposes. In addition, the Consortium will explore the ethical, legal, and social implications (ELSI) of integrating ML/AI tools into genomic medicine through the establishment of a framework for ELSI studies and through implementation of ELSI research projects.
Applicants interested in applying to this NOFO should read the companion NOFO carefully and understand the roles and expectations from the MAGen Site awardees and understand the goals of the Consortium.
Given the risks involved in achieving MAGen goals e.g., selection of suitable gene sets, drafting of a suitable framework for ELSI studies, the capability to undertake cross-validation, the challenges around converging data models among others, this NOFO utilizes a UG3/UH3 cooperative agreement mechanism which entails a Two-Phase, one-application approach to accomplish the goals. The focus of the UG3 Phase is the development of necessary Consortium-wide consensus around the risks identified above and other aspects that could impact achieving the goals of the MAGen consortium. The focus of the UH3 Phase (if successful) will be the actual development and execution of the consensus approach developed in the UG3 Phase. The objectives of the MAGen CC in the two Phases are:
UG3 - Design Phase (Years 1-2)
Transition from UG3 to UH3 Phase
Four months prior to the expiration of the UG3 award, the recipient will need to submit the transition package which will include the UG3 report delineating progress toward achieving UG3 milestones and activities, as well as the milestones proposed for the UH3 phase. This application will be administratively reviewed internally by the NHGRI for consideration for the UH3 phase award. Thus, recipients of the UG3 awards should note that there is no guarantee of a subsequent UH3 award. Consideration for the UH3 award is contingent upon submission of this transition package and satisfactory progress towards the UG3 milestones.
The criteria to determine the continuation to the UH3 Phase will be based on the satisfactory progress of the MAGen CC in meeting the Consortiums milestones and deliverables. Such criteria include but are not limited to:
In the event of an UH3 award, all recipient PD/PIs and the NHGRI staff will negotiate the final list of milestones for the entire Consortium for each year of support.
UH3 - Development Phase (Years 3-5)
Data sharing
Recipients are expected to comply with the NIH Data Management and Sharing Policy (NOT-OD-21-013) and NIH Genomic Data Sharing Policy (NOT-OD-14-124). NHGRI supports the broadest appropriate data sharing with timely data release through widely accessible data repositories. Please follow the NIH guidance on writing a Data Management and Sharing (DMS) Plan here, and ensure the Plan is in alignment with NHGRIs data sharing expectations, which are summarized at genome.gov/data-sharing.
Consortium Formation and Governance
This NOFO uses the Cooperative Agreement mechanism. Successful applicants will become members of the Consortium comprising investigators funded in response to either one of the two NOFOs: RFA-HG-24-004 and RFA-HG-24-005.
A Steering Committee (SC) will be the main governing body of the Consortium. The SC will be composed of the PD(s)/PI(s) from each Consortiums award and NIH program staff. In addition to the PD(s)/PI(s), key personnel from each Site and working group representatives will be eligible to attend SC meetings. The SC will establish subcommittees or working groups to facilitate collaborative work and to achieve the Consortiums goals. Major scientific decisions such as the framework for ELSI, identification of genes, variants, and datasets to be used for tool development, data model, tool requirements, cross validation plans, ESLI Research projects, Consortium milestones etc., will be determined by consensus, and as needed, by majority vote of the SC, where each funded Site, the MAGen CC, and the NHGRI will each have a single vote. The SC will meet regularly and be assisted by the activities of working groups.
An External Scientific Panel (ESP) of independent experts will provide input on performance, priorities, and overall progress of the Consortium, including the administrative review of the Consortiums accomplishments for the transition from the UG3 to UH3 phase. The ESP will consist of individuals with a broad range of expertise, including multi-modal data, ML/AI tool development, software engineering, clinical research physicians, and ethicists/social scientists, and other areas as needed. The ESP will meet semi-annually (one conference call and one in-person meeting per year), in conjunction with Steering Committee meetings, as appropriate. Following each meeting, the ESP will generate recommendations for the SC to consider and respond to.
Informational Webinar and Frequently Asked Questions
An informational webinar will be held for potential applicants. During the webinar, NHGRI staff will present overviews of both this and its companion NOFO and answer questions from prospective applicants. The informational webinar is open to all prospective applicants, but participation is not a prerequisite for submission of an application. Time, date, and dial in information will be posted at: https://www.genome.gov/event-calendar/MAGen-NOFO-Webinar. The webinar connections will open 15 minutes in advance of the start time. A recording of the webinar will be posted on the above website, together with a list of Frequently Asked Questions from the applicants.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.
The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Not Allowed: Only accepting applications that do not propose clinical trials.
NHGRI intends to commit $1.2M in FY 2025 to fund 1 award.
Application budget is limited to $800,000 per year direct costs, for five years.
The project period for this NOFO is 5 years (FY2025-FY2029).
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 not allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information
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 How to Apply - Application Guide.
2. Cost Sharing
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.
3. Additional Information on Eligibility
Number of Applications
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
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:
The letter of intent should be sent to:
Ajay Pillai, Ph.D.
Email: ajay.pillai3@nih.gov
Page Limitations
All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.
SF424(R&R) Cover
All instructions in the How to Apply - Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the How to Apply - Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the How to Apply - Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the How to Apply - Application Guide must be followed.
R&R Budget
All instructions in the How to Apply - Application Guide must be followed.
Budgets should include costs for hosting regular teleconferences and meetings of the SC and its working groups. Include the costs for organizing and hosting a virtual kick-off meeting of the Consortium to be held within 30 days of award. The budget should include the costs to organize and host one annual in-person (2 days, 1-2 nights) Consortium-wide meeting for the UG3 and UH3 Phases. The MAGen CC should budget for twice monthly SC virtual meetings in the UG3 Phase, and monthly SC virtual meetings in the UH3 Phase and other virtual meetings as appropriate. The budget should include travel costs for 8 ESP members.
Discuss how the unique composition of the research team will ensure successful completion of the project. Effective management of the MAGen CC requires a significant commitment by the Program Director(s)/Principal Investigator(s). For an application proposing a single PD/PI, the PD/PI is expected to devote at least 1.2 person months annually to the project. The budget should include support for a dedicated Project Manager who will devote a minimum of 6 person months. The appropriateness of the effort of key personnel must be justified in the budget justification.
Costs for any cloud, or storage and computing infrastructure proposed for data model and cross validation environment development and maintenance should be included and justified in the budget.
The budget should include any funds required to support sharing of scientific data under this NOFO, as per guidance on allowable costs for data management and sharing on its Budgeting for Data Management & Sharing webpage.
R&R Subaward Budget
All instructions in the How to Apply - Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the How to Apply - Application Guide must be followed.
PHS 398 Research Plan
All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:
Research Strategy
Specific Aims: Provide the overall goals for the entire application. The Specific Aims section should include distinct Aims for the UG3 and UH3 phases. Applicants must submit a single application that includes both the UG3 and UH3 phases.
Research Strategy: Organize the Research Strategy in two separate UG3 and UH3 subsections. For each subsection (UG3 and UH3), the significance, innovation, and approach should be clearly highlighted. Do not repeat information or experimental details in the UH3 section that are already described in the UG3 section. The MAGen CC is expected to support the Consortiums collaborative activities. These are outlined for each of the UG3 and UH3 phases in the section titled Research Objectives, Scope, and Approach in Section I of this NOFO. These include the criteria specified under Technical and Scientific Coordination and Serve as an Administrative and Coordinating Center. Note that these involve some activities with primary responsibility to the CC and others where the CCs role is guidance and facilitation. Driving the Consortia towards consensus is an important goal of the applicants to this NOFO and applicants are encouraged to propose innovative approaches; this will entail adaptability and willingness towards flexibility around the proposed approaches. Applicants should propose plans, approaches, benchmarks for success and risk mitigation strategies to achieve the goals of this NOFO.
Provide an overall operational plan and organizational structure to accomplish the goals of this NOFO. Given the highly collaborative nature of the Consortium activities, and the inter-relatedness between the tasks in each of the phases, describe innovative approaches for supporting technical and administrative coordination. For MAGen Consortium to succeed in its aims it will need to arrive at a consensus on many challenges (as outlined in Section I of this NOFO) and the applicant is encouraged to propose innovative methods that would drive the Consortia towards required consensus. Describe the approach to bring diverse teams together to enable synergistic and collaborative team science across the Consortium, and evidence of strong leadership complemented by scientific insight. Risky aspects, potential problems and alternative strategies for risk mitigation should be provided.
Provide a staffing plan and describe the expertise of the proposed team to support Consortium-wide activities. Demonstrate scientific expertise in data model development for multimodal datasets, and to support the coordination of ML/AI tool development and cross validation activities in a cloud environment in translational research settings.
Provide approaches for timely, effective, and efficient sharing of resources within the Consortium, and for disseminating them to the research community.
Milestones (required): Applicants must include a section entitled Milestones and provide milestones for BOTH the UG3 and UH3 phases of the award within the research strategy. Provide semi-annual quantitative and qualitative milestones. Within this section, describe the suitability of the chosen milestones to achieve the goals for transition to the UH3 phase and to complete the goals for the UH3 phase. The milestones should be specific, scientifically rigorous, and not simply a restatement of the Specific Aims. They should address critical points of the proposed program and describe research outcomes by providing quantifiable measures for success within the UG3 and UH3 phases of the award.
Applicants are alerted that given the highly collaborative nature of the consortiums activities, these milestones may be renegotiated prior to and during the award period.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.
NHGRI is committed to the timely release of well-documented open-source software and analyses including models and tools developed from proposed studies. Applicants should describe a plan for open dissemination of methods, protocols, software, and tools to the community such that they are readily usable and extensible, where applicable. Methods, protocols, tools, and software should be well-documented and where applicable made available via version-controlled public repositories including AnVIL as appropriate.
For a list of frequently asked questions about Best Practices for Sharing Research Software, see https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq.
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 How to Apply - Application Guide must be followed, with the following additional instructions:
To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community for research use in the AnVIL platform as possible and appropriate, through submission of variant interpretations to ClinVar, and through publication in the scientific literature.
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the How to Apply - Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.
PHS Assignment Request Form
All instructions in the How to Apply - Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
4. Submission Dates and Times
Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIHs electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
6. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.
7. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.
The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organizations profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review 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 troyerj@mail.nih.gov when the application has been submitted. Please include the FON 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.
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.
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 NOFO:
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 NOFO:
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?
Specific to this NOFO:
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 NOFO:
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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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.
Not Applicable.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
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.
Not Applicable.
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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.
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.
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 policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.
Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.
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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.
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.
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:
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.
If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigators 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.
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 System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicants integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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 (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist/Scientific Officer (PS/SO) at NHGRI is a dual role held by a NHGRI Program Director. The PS/SO will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. The PS/SO will be responsible for the normal scientific and programmatic stewardship of the award. The role of NHGRI PS/SO will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Consortiums members and NIH staff will offer input to this process.
This NOFO is a milestone-driven cooperative agreement program using the UG3/UH3 Cooperative Agreement mechanism involving NIH program staff in the negotiation of the final project plan before and during the award period, and monitoring of research progress. NHGRIs funding for the MAGen Sites and the MAGen CC will be based on the satisfactory progress of the whole Consortium in meeting the Consortiums milestones and deliverables. The PS/SO will participate as a member of the SC and will have one vote. The PS/SO will be named in the Notice of Award and will have the following substantial involvement:
Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium decides to publish, participating in data analyses, interpretations, and co-authorship of the publication of Consortium results through their role in scientific program management.
Areas of Joint Responsibility include:
Close interaction among the participating Consortium member teams will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to meet the goals of this NOFO. The recipients and the Project Scientist will meet regularly as the program SC.
The SC will be the main governing body of the Consortium. The SC will be composed of the PD(s)/PI(s) from each Consortiums award and NIH program staff. In addition to the PD(s)/PI(s), key personnel from each Site and working group representatives will be eligible to attend SC meetings. The SC will establish subcommittees or working groups to facilitate collaborative work and to achieve the Consortiums goals. Major scientific decisions such as the ELSI Framework, identification of genes, variants, and datasets to be used for tool development, data model, tool requirements, cross validation plan, ELSI research projects, Consortium milestones etc., will be determined by consensus, and as needed, by majority vote of the SC, where each funded Site, the MAGen CC, and the NHGRI will each have a single vote. The SC will meet regularly and be assisted by the activities of working groups.
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.
3. Data Management and Sharing
Consistent with the 2023 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 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), 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 2 CFR Part 200.113 and Appendix XII to 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 (Responsibility/Qualification in SAM.gov, formerly 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 2 CFR Part 200 – Award Term and Condition 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: 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Ajay Pillai, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone:
Email: ajay.pillai3@nih.gov
Christine Cutillo
ODSS - Office of Data Science Strategy
Phone: none
E-mail: christine.cutillo@nih.gov
Rudy, Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-219-6235
Email: pozzattr@exchange.nih.gov
Lisa Oken
National Human Genome Research Institute (NHGRI)
Telephone: 301-594-5250
Email: Lisa.Oken@nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.