Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Funding Opportunity Title

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Analysis and Validation Centers (U01 Clinical Trial Not Allowed)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HG-21-030

Companion Funding Opportunity

RFA-HG-21-029 - Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Production Research and Development Centers (UM1)(Clinical trials not allowed)

RFA-HG-21-031 - Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Resource and Administrative Coordinating Center (U24 Clinical trials not allowed)

Assistance Listing Number(s)

93.172

Funding Opportunity Purpose

This FOA is one of three issued to create a new program called "Molecular Phenotypes of Null Alleles in Cells (MorPhiC)". The long-term goal of MorPhiC is to develop a consistent catalog of molecular and cellular phenotypes for null alleles for every human gene, using in vitro multicellular systems. The catalog will be made available for broad use by the biomedical community. The program will start with a Phase 1 to optimize available methods to create null alleles and measure their phenotypic effects in a target subset of 1000 protein coding genes across the program. Phase 1 will also assess the scale limitations of such methods, develop common data formats, establish “use cases” for this catalog, and inform whether and how a potential second phase will be implemented. This specific FOA seeks applications for MorPhiC Data Analysis and Validation Centers. These Centers will develop computational models and data analysis and visualization methods to evaluate and help ensure the utility of the MorPhiC data. Separate FOAs will be issued for the two other components of MorPhiC: Data Production Research and Development Centers and a Data Resource and Administrative Coordination Center to receive, annotate, and present data for consortium and public use and to be the administrative coordinating center for the MorPhiC consortium.

Key Dates
Posted Date

August 6, 2021

Open Date (Earliest Submission Date)

October 1, 2021

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

November 1, 2021

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s)

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.

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

March 2022

Advisory Council Review

May 2022

Earliest Start Date

September 2022

Expiration Date

November 2, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

    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


    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    The 2020 NHGRI Strategic Vision (https://www.genome.gov/2020SV) laid out a set of “bold predictions for human genomics by 2030” that included: “The biological function(s) of every human gene will be known; for non-coding elements in the human genome, such knowledge will be the rule, rather than the exception.” In addition, the Strategic Vision states that recent advances in knowledge and technology "… provide an unprecedented opportunity to decipher the individual and combined roles of each gene and regulatory element. This must start with establishing the function of each human gene, including the phenotypic effects of human gene knockouts".

    Systematically obtaining information about the molecular and cellular phenotypic effects of gene knockouts for all human genes would provide wide-ranging insights into the biological function of genes filling a gap between more direct molecular readouts, such as RNA expression, and whole-organism phenotypes. Such data would provide a foothold for understanding the mechanisms through which genes act to produce phenotypes and would help elucidate the roles and relationships of genes and regulatory elements in pathways and networks, as called out as one of the "compelling genomic research projects" in the NHGRI Strategic Vision.

    Based on these considerations, NHGRI is initiating a new program, the Molecular and Cellular Phenotypes of Null Alleles (MorPhiC) Consortium, with the long-term goal of developing a consistent catalog of informative molecular and cellular phenotypes for null alleles for every human gene, using in vitro multicellular systems.

    • The catalog should be consistent, that is, generated using standardized assays and providing a comparable level of phenotype information for each gene. Consistent data enables comparisons between genes, computational modeling, and integration with other functional and phenotypic data.
    • The catalog should include informative molecular and cellular phenotypes. We interpret the word "assays" broadly-- for example, they may go beyond the usual molecular -omics assays to include cell shape and motility, survival/differentiation, and other phenotypes. Genes often have multiple cellular roles and participate in multiple processes, making this goal challenging. MorPhiC therefore does not aim to catalog every function of each gene assayed, but to catalog a core, well characterized "minimal set" of functional information for each gene that is as informative as possible for understanding biological processes. We envision a handoff, where downstream users will combine this information with other functional data to more thoroughly characterize specific genes, or sets of genes, in specific contexts.
    • Null alleles—generally, those producing no functional protein—are useful as a basis for interpreting other alleles, including regulatory alleles that may have weaker effects (e.g., lower penetrance and expressivity), and gain-of-function alleles. A null allele is also useful for interpreting alleles of other genes that produce similar or “opposite” phenotypes, and interpreting effects of other perturbations (e.g., small molecule or environmental exposures). Alternatives may be required if the homozygous null cannot be assayed (e.g., is cell lethal in an assay--see below).
    • While the long-term goal of MorPhiC is to be comprehensive with respect to genes, the Phase 1 goal is to target 1000 protein coding genes. This number will be large enough to attain the Phase 1 goals, allowing for diverse genes (with regard to e.g. tissue, functional class, disease relevance) to be tested, and to allow for useful overlap to test the same gene in multiple assays, or for quality assessment.
    • MorPhiC will catalog molecular and cellular phenotypes using multicellular systems that are likely to be informative of human biology, while at the same time having the potential for scalability and reproducibility. This initiative has a strong preference for complex multicellular systems-- such as organoids-- for several reasons. Mainly, they have the potential to more faithfully model human tissue-level phenotypes. Technological advances in this field are well-supported, so the state of the art is likely to improve substantially in the near-term. Moreover, NHGRI (and others) already support multiple other efforts to look at phenotypes in monotypic cell cultures.

    Phase 1 of the project will explore the feasibility of developing the MorPhiC catalog and inform its ultimate value. Specifically, the goal of Phase 1 will be to optimize available methods to create null alleles in a target subset of coding genes and to measure their phenotypic effects in multi-cellular systems. It will test the feasibility of integrating the key technical components into a beginning production pipeline. Phase 1 will also assess the scale limitations of such methods, identifying technical and other bottlenecks, and understanding cost drivers. It will develop common data formats. It will examine the ability to use the data to address different kinds of biological questions in order to understand the value of the data, as a whole, and to understand which particular assays may be the most valuable for MorPhiC. All of this will be used to assess the feasibility of a potential second phase.

    To achieve the goals of Phase 1 of MorPhiC the following three FOAs are issued:

    • Data Production Research and Development Centers (DPC) RFA-HG-21-029 to develop, implement and compare approaches for obtaining null alleles in human cells, and to assess and catalog the resulting molecular and cellular phenotypes. This FOA is for the DPC component.
    • Data Analysis and Validation Centers (DAV) RFA-HG-21-30 (this FOA) to evaluate and ensure utility of the generated data and to begin to use them in analysis.
    • Data Resource and Administrative Coordinating Center (DRACC) RFA-HG-21-031 to receive, integrate, annotate, and present data for consortium and public use, and provide logistical support for the consortium.

    The data and analyses performed in Phase 1 will substantively advance our knowledge of gene function and how to design large-scale approaches to understanding gene function. However, one potential outcome of MorPhiC Phase 1 may be that it is not feasible to achieve the scale, consistency, utility, and interpretability to move to a Phase 2, as evaluated by NHGRI.

    Proposed Scope and Objectives:

    The high-level intent of the Phase 1 MorPhiC Consortium is to confront the "Main Barriers" to initiating a full-scale effort, including:

    • What is the optimal way to make null alleles at scale for this purpose? What quality assessment (QA) is needed to ensure these are null alleles? Is there one method that would be compatible with all genes and informative assays? Can existing resources (e.g., libraries of iPSC knock-out lines) be leveraged, or do alleles need to be created? Do we need alternatives to true null alleles in some cases?
    • How can we prioritize the 1000 genes to represent a fair test of generalizability across the genome and organism? What human multicellular systems will be scalable, reproducible, and highly informative about human biology? Are organoids and similar systems currently sufficiently reproducible?
    • What are the best assays, or assay strategies/combinations for measuring molecular and cellular phenotypes? Are assays going to yield readouts that are specific and informative about complex organismal phenotypes? How do we maximize how informative the assays are? Can assays be made more generalizable?
    • How can we anticipate and address, or even take advantage of, potential technical and interpretation issues due to underlying biology, such as: cell- or tissue-type specificity, pleiotropy, cell lethality, haploinsufficiency, cell non-autonomy, natural biological variability?
    • What is the ultimate utility of the data for various purposes? Across all genes, will molecular and cellular assays of null alleles in humans be informative for understanding gene function in basic and clinical applications? Does the proposed catalog provide data in ways that elucidate the roles and relationships of genes and regulatory elements in pathways and networks?
    • What quality and consistency of data is needed? What is the best way to manage and organize the data and present it to the community? What is needed for these data to be interoperable and highly useful in combination with other "perturbation X phenotype" data sets, such as those generated by IGVF (https://www.genome.gov/Funded-Programs-Projects/Impact-of-Genomic-Variation-on-Function-Consortium ), or the Knock Out Mouse Program (KOMP; https://www.mousephenotype.org/about-impc/about-komp/ )?
    • What are the major bottlenecks and cost drivers? Where can costs be reduced?
    • What insights can we gain about the best way to organize a full-scale effort for a potential Phase 2?

    This list is not exhaustive. Moreover, some of these challenges are evident now, and some will only become evident as Phase 1 progresses.

    This FOA seeks applications for the MorPhiC Data Analysis and Validation (DAV) centers. The primary goals are to demonstrate that the (1) data variability is controllable, (2) data is useful to understand basic biological processes, and (3) data is interpretable for undertaking future hypothesis-driven science by the community. In order to maximize the likelihood that MorPhiC data will be useful to the community, DAV centers should with feedback from the community assess data quality, utility, ability to integrate with other community data resources (see below). Efforts within the DAV centers is intended, ultimately, to maximize the likelihood that the data will be useful to the community. Other important FOA goals are to develop methodologies that develop broadly useful computational and analytic methods using MorPhiC and non-MorPhiC data as well as methods that produce novel biological insights.

    It is essential to develop an understanding of the goals of the program and to obtain a good idea about the cellular systems and assays that might be in scope for the program and how data and metadata will be collected and handled. This can be achieved by reviewing the companion FOAs (RFA-HG-21-029, RFA-HG-21-031) and by communicating with program staff.

    Specific example scientific questions include (but are not limited to):

    • Creating appropriate statistical methods to model technical and biological variation in MorPhiC data. For example, methods that can disentangle variation in a specific assay modality from variations in multiple assay modalities.
    • Methods that can address any potential genomic, or population- or sex-based variability to understand variation in molecular readouts in complex human cultured cells.
    • Identifying a small number of cellular phenotypes that strongly associate with model organism or human phenotypes from MorPhiC and other data.
    • Building integrative & "explainable" models that can help the consortium prioritize which genes to knockout in which cellular systems.
    • Building predictive models of untested perturbations and/or untested systems and using these models as a vehicle for experimental design within the MorPhiC consortium.
    • Inferring phenotypes from existing data and validating using MorPhiC data.
    • Modeling fundamental biological processes (e.g., cell fate determination, cell death) based on perturbation data to obtain causal models.
    • Building novel visualizations of complex data generated in MorPhiC that can take prior knowledge into account.
    • Validating the Application Programming Interfaces, and data formats and standards to enable the community to undertake integrated data analysis across resources spanning MorPhiC and other programs like IGVF or KOMP.

    This is not intended to be an exclusive list—applicants may point out and justify other important uses of MorPhiC data that we may not have explicitly included here.   

    Research proposed should have a high potential to illuminate strengths and weaknesses of MorPhiC data. Enabling the community, especially smaller laboratories with limited bioinformatics expertise, to effectively use models built around MorPhiC and other functional genomics data is a continuing need, i.e., this FOA hopes to make it possible for a diverse set of labs to undertake hypothesis-driven research based on data hosted by the DRACC (RFA-HG-21-031). Thus, the software and models generated should be openly and effectively shared with the community. Careful thought should be given to making it possible for small labs to efficiently build simple tools using frameworks based on R or Python will enable effective dissemination of MorPhiC data and tools.

    Year 1 activities: Data not generated as part of MorPhiC can be used for modeling. Year 1 activities are special since there will be no MorPhiC data available. Thus, projects will devote substantial fraction of their year 1 effort on the following: (1) building models using existing data that will support experimental design efforts within the consortium while making the data and models available to the DRACC to share with the community; (2) consortium planning efforts towards making choices about the standards, metadata, and other important elements to enhance overall goals of the consortia.

    Non-responsive Applications:

    Projects with the following properties will be considered non-responsive, and will not be reviewed:

    • Projects that propose wet-lab data generation.
    • Projects that propose to build models only for a small subset of perturbation targets or cellular systems.
    • Projects that are not focused on the downstream phenotypic consequences of null alleles in humans. Projects that test cis-regulation or noncoding variants (except those strategically designed to produce null alleles) are not responsive.
    • Projects that do not use MorPhiC data or other similar datasets.
    • Projects that do not propose plans to assist with experimental design strategies.
    • Proposed work that does not indicate plans to participate to contribute to consortium-wide, collaborative activities and analyses throughout the course of the project.
    Consortium Formation and Collaboration

    This FOA uses the Cooperative Agreement mechanism. The key objectives of MorPhiC Phase 1 can only be realized by coordinating among what are likely to be diverse approaches, leading to the need to organize MorPhiC into a consortium.

    Successful applicants will become members of the MorPhiC Consortium composed of investigators who have been funded in response to one of the three companion FOAs. Awardees are expected to work collaboratively with all members of the consortium towards meeting consortium goals, in addition to the research goals outlined in their individual applications. Synergies among the different components will be identified by the consortium and pursued to generate a better understanding of how to produce the long-term catalog.

    For the DPCs, the most important collaborative task will be to prioritize and assay the Phase 1 1000 genes, and to develop standards and methods to ensure comparability, reproducibility, complementarity, etc. of assay results. Once awards are made, successful applicants will be asked to collaborate to develop common plans to prioritize genes, and assay the effects of the null alleles, as efficiently and reproducibly as possible, across the consortium.

    Awardees will also be required to work collaboratively with the other MorPhiC components as they are stood up.

    At key points during Phase 1, the consortium will be asked to critically evaluate the approaches taken and their potential for long-term inclusion in a full catalog.

    Awardee consortium responsibilities will include:

    • Planning experiments, implementing studies, and analyzing results from within component and consortium-wide projects, typically through working groups including all Consortium components.
    • Developing standards and metrics for data, metadata, data quality, and analyses together with the DRACC (RFA-HG-21-031) and DPC (RFA-HG-21-029).
    • Contributing all data, metadata, protocols, methodologies, analyses, software, and other products to the DRACC and appropriate repositories in specified formats. NHGRI supports the broadest appropriate genomic data sharing with timely data release through widely accessible data repositories. If applicable, awardees are expected to comply with the NIH Genomic Data Sharing (GDS) Policy https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing. More information on this expectation can be found on NHGRI's Genomic Data Sharing Policy FAQs.
    • Sharing best practices and lessons learned within the consortium and with the external community.
    • Participating in the development of, and following consortium policies on, data sharing and publication.
    • Taking part in consortium-wide, Steering Committee, and working group meetings.
    • Contributing to outreach efforts, including collaborating with other consortia and projects.

    All investigators will be required to attend a kickoff meeting for the consortium that will take place soon after awards are made. A major focus of the kickoff meeting will be establishing the consortium's scientific direction and interactions within and between components. A Steering Committee composed of the funded PDs/PIs and NHGRI staff will be established to guide the overall scientific direction of the consortium. The Steering Committee will meet regularly and be complemented by a set of working groups. NHGRI staff will also recruit outside experts (non-awardees) as an External Scientific Panel to provide advice directly to NHGRI.

    Diverse Applicants

    NHGRI strongly encourages all investigators with innovative ideas aligned with the goals of this FOA to submit applications. NHGRI especially encourages applicants who are new investigators, experienced investigators who are new to genomic science, investigators that have not previously participated in a NHGRI consortium or program, and investigators from demographic groups or institutions that are generally underrepresented in genomic science.

    Informational Webinar

    All applicants are strongly encouraged to contact NHGRI Staff to discuss the responsiveness and alignment of their proposed work with the goals of this program. An informational webinar will be held for potential applicants. NIH staff will be available to answer questions related to this FOA. The Webinar will occur on September 10, 2021, at 1-3 PM US Eastern DST. Further information will be posted on the NHGRI website: https://www.genome.gov/event-calendar/MorPhiC-pre-application-webinar or can be obtained from the Program contact (below). During the webinar, NHGRI staff will present overviews of the FOAs and answer FOA-related questions from prospective applicants. Questions may be submitted in advance to morphicprogram@nih.gov. Frequently asked questions will be posted afterwards. The informational webinar is open to all prospective applicants, but participation is not a prerequisite for submission of an application.

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support 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 FOA.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

    NHGRI intends to commit $1.5M in FY 2022 to fund 2-3 awards.

    Award Budget

    Application budgets need to reflect the actual needs of the proposed project but should not exceed $300K direct cost per year.

    Award Project Period

    The maximum project period is five years.  

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    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)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    • Non-domestic (non-U.S.) Entities (Foreign Institutions)
    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.

    Required Registrations

    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.

    Eligible Individuals (Program Director/Principal Investigator)

    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.

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

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

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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).

     

    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. 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 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.

    Letter of Intent

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

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

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

    The letter of intent should be sent to:

    Ajay Pillai, Ph.D.
    Email: morphicprogram@nih.gov

    Page Limitations

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

    Instructions for Application Submission

    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.

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    SF424(R&R) Senior/Key Person Profile

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

    R&R or Modular Budget

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

    • For single PD/PI applications, the PD/PI is expected to devote at least 1.2 person months, based on a 12-month calendar. If multi-PDs/PIs are proposed, then at least one PD/PI is expected to commit at least 1 calendar month annually and the other(s) should devote sufficient time to serve his/her proposed role with a minimum aggregate of 1.2 person months. The appropriateness of the effort of key personnel must be justified in the budget justification.
    • Budget can be requested for project management support that might be required in Consortia. For this FOA it is not expected to be excessive, and the PD/PI can act as the project manager.
    • Budgets should include funds for the PD(s)/PI(s) and key personnel to attend the initial consortium kickoff meeting, and for the PD(s)/PI(s) and 2-4 members of the center to attend annual consortium meetings thereafter that start in year 1.
    • Budgets should include any funds required to support sharing relevant non-MorPhiC data under this FOA to the MorPhiC DRACC.
    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    • Overview
    • Research Proposal
    • Collaborative Activities

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

    Overview

    Provide an overview of the proposed Analysis and Validation Center and how it will be structured to achieve the center’s goals and the major objectives of the FOA. This should include a high-level description of the strategic approach proposed (importance of biomedical questions addressed including choice of computational methods, relevance beyond in-vitro settings, choice of non-MorPhiC data, adapting as necessary to MorPhiC data), along with the high-level rationale behind those choices, with details to be covered in the subsections below. The overview should provide a sense of how the proposed Phase 1 effort will contribute methods that evaluate the strengths and weaknesses of MorPhiC catalog, and, more generally, contribute to the understanding or interpretation of gene and/or pathway function. Any planned technical, strategic, methodological, analytical, or other innovation may be highlighted.

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

    Outline how Diversity perspective (see Section I) has been addressed.

    Research Proposal

    This section constitutes the bulk of the proposal.

    • Please describe your plans for the project and how it reflects the goals described in section I above.
    • Innovative and state-of-the-art elements should be highlighted.
    • Clearly delineate activities proposed in Year 1 separately from the following years (see FOA Goals and Objectives section above that describe why Year 1 is special). Explain and justify the choice of non-MorPhiC data being proposed to be used.
    • Clearly explain how you will adapt/change to address the data that will be produced within MorPhiC since that will not be known at the time of application.
    • Clearly explain how your project will benefit and enable the wider community, including impact on how it will help hypothesis-driven studies. Interpretability of models is important in enabling hypothesis-driven studies and so these aspects should be highlighted.
    • Clearly delineate any timelines and milestones.
    Collaborative Activities

    Collaborative activities within the Consortia are crucial for the success of the MorPhiC program. Applicants should identify (while recognizing that needs will change during the funding period) key analytical challenges they will collaborate on. This subsection should emphasize the role of their research proposal and strengths of the personnel involved in helping the consortia address its Phase 1 goals over the span of five years. A willingness to work within a Consortia needs to be clearly articulated and specified in as much detail and specificity as possible. It is important to specify the requirements and flexibility available for deploying their models at the portal being developed by the DRACC.

    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:.

    • Consistent with the goals of this program, Data Sharing Plans are required for this FOA. Applicants must address all points below.
    • In their Data Sharing Plans, applicants should indicate their willingness to abide by all data deposition, data quality metrics, standards and metrics for data, metadata requirements, and data/software release policies developed by the Consortium's Steering Committee and approved by NHGRI staff. Awardees are expected to develop such policies as members of the consortium's Steering Committee in collaboration with NHGRI and should indicate their willingness to participate in the development of such policies and to accept them. These policies will remain consistent with NIH and NHGRI policies on data and resource sharing.

    Plan for Data Sharing: A key long-term goal of the MorPhiC Consortium is to build a durable community resource of data, models, and tools designed and built to enable future adoption in building a full catalog. At the same time, we expect the phase 1 data on their own will be included in the catalog and will be used by researchers for diverse analyses. For this FOA data includes any annotations generated by computational or other expert curation methods or those generated by collaborative efforts with the larger community. Applicants must propose a data sharing plan consistent with this goal that addresses rapid data sharing with the community and describe plans to assist the DRACC to adhere to the FAIR Guiding principles (Findable, Accessible, Interoperable, Reusable), including:

    • Data and metadata assigned unique and persistent identifiers.
    • Data and metadata retrievable using standardized protocols/APIs.
    • Data pass strict quality metrics.
    • Data have clear provenance.
    • Rich metadata are collected with all data.

    Wherever possible, community-standard formats, vocabularies, ontologies, quality metrics are to be used. Note that, once the consortium is formed, we expect to develop cross-consortium policies for data sharing; this will be led by the DRACC (see Companion FOA, RFA-HG-21-031).

    Selection of Biological Samples, Ability to Share Data with Community: Non-MorPhiC data proposed for analysis should reflect the below considerations and any exceptions should be explicitly justified.

    In order to maximize the utility of the data, all human biological samples to be studied that are derived from specimen or cell line sources are expected to have been obtained using a documented informed consent process that explicitly allows for future research use and broad data sharing (NOT-HG-20-011). Sources with participant consent for unrestricted access are strongly encouraged. Sources consented for sharing through a controlled-access environment, such as General Research Use (GRU) or Health, Medical, and Biomedical (HMB) without additional restrictions, will also be considered and should be well justified. The consent process for human biological samples should be described at a high level in the Research Plan and detailed in the Data and Resource Sharing Plans.

    Studies should include samples that are derived from individuals of diverse ancestry and allow for consideration of sex as a biological variable. Applicants may propose study of genes and assay systems with consideration of diseases disproportionately affecting disadvantaged or under-represented populations.

    Plan for Software and Data Analysis Sharing: NHGRI is committed to the timely release of open source software and well-documented data analyses including models and tools developed from proposed studies. Applicants should include plans for open dissemination of methods, software, and tools to the community such that they are readily usable and extensible, where applicable. These should be made freely available to biomedical researchers and educators. There is no prescribed license for software produced by applications responding to this announcement, but any software license selected by applicants should allow for unrestricted redistribution and modification of software.Methods, protocols, tools, and software should be well-documented and where applicable made available via version-controlled public repositories.

    Where applicable, applicants should describe solutions for portable implementations.

    Solutions that enhance reproducibility when used by the community and ability of the community to integrate into automated pipelines should be emphasized.

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

    Appendix:

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

    PHS Assignment Request Form

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

    Foreign Institutions

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

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

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

    4. Submission Dates and Times

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

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

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

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

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

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

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

    7. Other Submission Requirements and Information

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

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

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

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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.

     

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    Overall Impact

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

    Scored Review Criteria

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

    Significance

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

    Specific to this FOA:

    • Will the proposed project contribute to addressing the challenges of a full-scale effort to develop a catalog of cellular and molecular phenotypes of null alleles in humans?   Does the application identify and address the key scientific questions and other barriers to assess MorPhiC data quality, variability, utility, and interpretability?
    • Does the proposal identify and justify the choice of analyses and its broad biomedical significance?
    • Are the choices for year 1 activities significant, important, and relevant to the following year activities and MorPhiC consortium goals?
    • Has the proposal adequately considered community needs?
    Investigator(s)

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

    Specific to this FOA:

    • ·    Has adequate leadership for the day-to-day project management activities (e.g., a project manager or sufficient PD(s)/PI(s) effort) been described? Does the management plan clearly describe how the effort will be managed? Are there clearly described roles and reporting relationships for key personnel?
    • ·    Does the applicant indicate a willingness to work with other centers and participate in Consortium activities?
    • ·    Does the team bring key analytical strengths to the consortium?
    Innovation

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

    Approach

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

    Specific to this FOA:

    • ·    Are the proposed approaches state-of-the-art, and capable of producing useful and interpretable models?
    • ·    Are the proposed approaches appropriate for the data types likely to be produced in the MorPhiC consortium?
    • ·    Are the milestones, timelines and goals proposed for the research project reasonable and appropriate?
    • ·    Are the plans outlined for collaborative work adequate?
    • ·    Are the plans to work within the consortium and diversity aspects adequately developed?
    • ·    Is the data sharing plan reasonable and appropriate?

    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?  

    Environment

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

    Additional Review Criteria

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

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

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

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

    Not Applicable.

    Renewals

    Not Applicable.

    Revisions

    Not Applicable.

    Additional Review Considerations

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

    Applications from Foreign Organizations

    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.

    Select Agent Research

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

    Resource Sharing Plans 

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Sharing Model Organisms; and (2) Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHGRII, 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 (NACHGR).

    . 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.  These include:
    • ·    Program balance, meaning the need for this program to include multiple approaches and perspectives to enhance the likelihood that program goals will be met.
    • ·    Potential to work effectively in large collaborative efforts or research consortia, which may be based on previous experience with NIH-funded research consortia, if applicable
    • ·    Adequacy of data sharing, software and analysis sharing and resource sharing plans
    • ·    Expansion of the community of genomic science to include new investigators, experienced investigators who are new to this field, and investigators from demographic groups or institutions that are generally underrepresented in genomic science
    • ·    Inclusion of new investigators and experienced investigators that are new to NHGRI consortia.
    • ·    Whether an applicant or applicant institution will be funded as a PD/PI through this or the other FOAs in the MorPhiC Consortium to encourage participation from a broader representation of the research community
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

    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.

    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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex.  This includes ensuring programs are accessible to persons with limited English proficiency.  The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS.  Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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

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

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

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

    • Determining research approaches, designing protocols, setting project milestones and timelines, and conducting research.
    • Ensuring that the data, software, resources, materials, etc. produced as part of this project are released appropriately according to the Resource Sharing Plan.
    • Preparing abstracts, presentations, and publications in a timely manner.
    • Adhering to policies regarding sharing of genomic and other types of data, data access, and standardized formats; timely publication; and intellectual property established by the NIH, NHGRI, and the consortium.
    • Not disclosing confidential information.
    • Interacting with other relevant NHGRI and NIH activities, as needed, to promote synergy and consistency among similar or related projects.
    • In order for the collaboration to be effective, PDs/PIs are responsible for:
    • ·    Collaborating with the Data Resource and Administrative Coordinating center (DRACC) and other members of the consortium.
    • ·    Ensuring that the grantee receives the appropriate approvals for sharing data between the DRACC and selected data repositories such as, AnVIL,?dbGaP, GEO, ?ClinVar and other appropriate public databases.
    • ·    Transferring, in a timely manner, detailed (sequence, variant, other genomic, functional, phenotypic) and related data and metadata, as appropriate, to the DRACC, using agreed-upon formats and processes, to facilitate dissemination of data more broadly through databases such as?AnVIL,?dbGaP, GEO or?ClinVar, and other appropriate databases.
    • ·    Collaborating with the DRACC to establish data formats and standards, to track and document collaborations and incoming samples, report findings, etc.
    • ·    Submitting periodic progress or summary reports in a standard format, including data production summaries and metrics of the use and impact on the community, agreed on with the NHGRI Project Scientist/Scientific Officer (PS/SO) or the Steering Committee (SC; see below).
    • ·    Sharing research resources, tools, and data of interest with other members of the consortium, consistent with achieving the goals of the project.
    • ·    Assessing and disseminating data, protocols, consent materials, and methods developed for or derived from the DRACC within and outside the Consortium.
    • ·    Abiding by common definitions, protocols, and procedures.
    • ·    Attending and participating in SC and other working group meetings and accepting and implementing decisions made by the SC and/or PS/SO.

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

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

    The PS/SO will have the following substantial involvement: 

    • Serving as a liaison, helping to coordinate activities among and for the awardees, including acting as a liaison to the NHGRI and as an information resource for the awardees about genome research activities. The PS/SO will also coordinate the efforts of the grantee(s)with other groups conducting similar studies.
    • Reporting periodically on the progress of the grantees to the NHGRI Director and to the National Advisory Council for Human Genome Research.
    • Assisting awardee(s) in the development, if needed, of policies for dealing with situations that require coordinated action, including coordination with other NIH, national or international efforts.
    • Providing advice on the management and technical performance of the award.
    • Assisting in promoting the availability of the data and related resources developed in the course of the award to the scientific community.
    • Being responsible for the normal scientific and programmatic stewardship of the award, including assessments of how well the awardee has met any milestones required for each year of funding.
    • Curtailing, withholding or reducing support for any awardee that fails to make satisfactory progress toward the work scope that NHGRI approved, has ethical or conflict of interest issues, or fails to comply with the Terms and Conditions of Award.
    • Involving NIH or NHGRI staff who may assist the awardee(s) as designated by the PS/SO.
    • Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium/Network decides to publish, co-authoring manuscripts through their role in scientific program management.
    • External Scientific Panel. The NHGRI PS/SO may engage external scientists with relevant scientific and consortium experience, who are not funded as part of the project and who agree to a confidentiality policy, to provide input and advice to the NHGRI PS/SO about the project. The PS/SO will appoint 4-6 scientists to the ESP and will determine the durations of service. Activities of the ESP could include: 
    • ·    Participating, as appropriate, in consortium meetings, Steering Committees calls, and the annual grantees’ meetings; a subset of ESP members may also meet remotely at other times during the project period, as needed. 
    • ·    Reviewing and evaluating the progress of grantees (individually or as a group) in achieving the goals of the project. 
    • ·    Recommending changes in priorities based on scientific advances within and outside the consortium. 
    • ·    Providing individual recommendations regarding any changes in the project or grant(s) as necessary. The PS/SO will use these recommendations to make project changes, as appropriate. 

    Areas of Joint Responsibility:

    If there are multiple awards working toward a common goal, close interaction between the participating grantee(s) and the PS/SO will be required, to manage, assess, and implement the award(s), goals of the consortium, etc. This is accomplished by: 

    • Establishing a Steering Committee (SC): The SC will be the main governing body of the Consortium. The purpose of the SC will be to recommend directions for the consortium consistent with achieving the project goals, develop consortium policies to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges, and opportunities for the consortium.
    • · Each funded cooperative agreement within the consortium will designate one senior investigator to participate in and be responsible for reporting at SC calls/meetings. Other members of each group may attend at the discretion of the designated representative, as needed to cover specific topics. For decisions that require a vote, each grant in the consortium will have one vote. The PS/SOs will be SC members, with one vote total for NHGRI.
    • Responsibilities of the SC will include: 
    • ·    Developing its own operating procedures.
    • ·    Determining meeting (frequency and format).
    • ·    Sharing information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.
    • ·    Establishing best practices for data QC, integration and collaborative analyses as appropriate.
    • ·    Setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
    • ·    Generating responses to ESP recommendations by deadlines agreed upon by the SC and ESP members.
    • ·    The PS/SO will assist and facilitate the group process and not direct it.

    The SC may establish subcommittees to oversee the development and implementation of consortium policies including data, software, or other releases, publications, and standards, etc. and to coordinate analyses. Subcommittees may be either permanent or time limited, may include additional experts, depending on the needs of the research. The PD(s)/PI(s) will be expected to play an active role in these working groups, as appropriate.

    It is expected that most of the decisions on the activities of the SC will be reached by consensus. If a vote is needed, at least 60% of the voting members must vote in favor of the proposal.

    NIH staff will review and approve policies developed by the SC. Awardees will be required to accept and implement policies approved by the SC. The PS/SO will assist and facilitate the group process and not direct it.

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NHGRI may be addressed by convening a Dispute Resolution Panel. It will be composed of three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement for one award, the first member may be chosen by that 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.

    3. Reporting

    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.

    Section VII. Agency Contacts

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

    Application Submission Contacts

    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: GrantsInfo@nih.gov (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: support@grants.gov

    Scientific/Research Contact(s)

    Ajay Pillai, Ph.D.
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-538-4811
    Email: morphicprogram@nih.gov

    Peer Review Contact(s)

    Rudy Pozzatti, Ph.D.
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-402-8739
    Email: pozzattr@exchange.nih.gov

    Financial/Grants Management Contact(s)

    Anneliese Galczynski
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-443-4935
    Email: anneliese.galczynski@nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    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.

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