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 Resource and Administrative Coordinating Center (U24 Clinical Trial Not Allowed)

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HG-21-031

Companion Funding Opportunity

RFA-HG-21-030 - Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Analysis and Validation Centers (U01 Clinical trials not allowed)

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)

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 a Data Resource and Administrative Coordination Center that will be responsible for handling consortium-generated data and disseminating this information to the wider biomedical research community, as well as providing administrative coordination.

Key Dates
Posted Date

August 6, 2021

Open Date (Earliest Submission Date)

October 1, 2021

Letter of Intent Due Date(s)

September 15, 2021

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
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 1000 protein coding genes and 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.
    • Data Analysis and Validation Centers (DAV) RFA-HG-21-030 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 (this FOA) to receive, integrate, annotate, and present data for consortium and public use, and provide administrative 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.

    Research Scope and Objectives

    This FOA seeks to establish a Data Resource and Administrative Coordinating Center (DRACC) for the MorPhiC Consortium. The DRACC will be responsible for establishing a repository of consortium-generated data and metadata, analyses and annotations, and related information that will enable future efforts to understand the function of protein-coding genes. The DRACC will be expected to work closely with other consortium components to develop standardized data submission, quality metrics, and processing. The DRACC will support modeling, visualization, and validation efforts by the Data Analysis and Validation Centers. The DRACC will disseminate the primary data, processed and annotated data, and associated visualizations to the research community via a web portal and via programmatic interfaces. In addition, the DRACC should develop methods to integrate with similar or complementary resources (e.g. KOMP). Finally, the DRACC will serve as an administrative coordination center and thus will lead outreach efforts and support consortium-led analyses.

    Applicants will need to provide general plans that address the potential data types and tools generated by the consortium and are expected to be flexible in the implementation of data management workflows. Review of companion FOAs by applicants is strongly encouraged to get a sense of the range of data that will be generated by the consortium.

    The specific objectives of the DRACC are to:

    • Receive, wrangle, and quality control (QC) primary data, develop a database for storage, and make data available for consortium and community use
    • Support modeling, visualization, and validation efforts by the Data Analysis and Validation Centers
    • Develop processing pipelines and a web portal to disseminate information to the biomedical research community.
    • Develop methods to integrate with similar/complementary resources
    • Serve as an administrative and coordinating center for the consortium

    Receive, wrangle, and quality control primary data, develop a database for storage, and make data available for consortium and community use. Initially, the DRACC will assess the consortium assays, methods, data types, and expected analyses to determine needed submission and processing pipelines and to establish a more defined plan for the consortium database and portal. Thus, the DRACC will develop specifications for data and metadata in collaboration with the consortium and establish data quality metrics. The DRACC will develop a database to store raw and processed data, protocols and metadata, annotations and analyses, and other products of the consortium consistent with the FAIR (Findable, Accessible, Interoperable, and Re-usable) Guiding Principles (https://www.nature.com/articles/sdata201618) to improve data sustainability and utility (see https://grants.nih.gov/grants/guide/notice-files/NOT-HG-21-022.html). To this end, primary data, metadata, or protocols may be deposited in other repositories, as appropriate. The DRACC will identify computational tasks and support those efforts by making data available in a suitable format. The database must be able to house all consortium-generated data and metadata for the duration of the project period and should be robust and scalable.

    Support modeling, visualization, and validation efforts by the Data Analysis and Validation Centers. A companion FOA will support the establishment of 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. The basic 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. The DRACC will collaborate with the DAVCs to accomplish these goals.

    Develop processing pipelines and a web portal to disseminate information to the biomedical research community. The DRACC will coordinate with the consortium to specify, implement, and run pipelines for processing of consortium-generated data. Processing may include effective summaries of the primary data, statistical analyses of various types, implementation of controlled vocabularies or ontologies for annotation purposes, or integration with existing pathway and network resources. Procedures, software, and other relevant information should be documented, accessioned, and shared with the broader research community, as well as any necessary training materials or tutorials. Access to this information and to consortium tools and analyses will be provided through a web portal developed and maintained by the DRACC. The portal should be accessible to the broader research community and include tools, for data exploration, query, and visualization that are responsive to community needs (computer scientists, biologists, and geneticists) and adhere to best practices in user interface design and operation. For example, providing the capability of faceted browsing can improve accessibility and enhance the exploration of biological useful subsets of data.

    Data are expected to be derived from several types of biological samples, including human samples. The DRACC should have experience with, and plans for, working with data that are consented for unrestricted data access as well as with controlled-access data and the registering and deposition of these data into appropriate repositories.

    Develop methods to integrate with similar/complementary resources. Because the overall goal of Morphic is to connect genotype to phenotype, interpreting the program data will be greatly facilitated by integration with similar and complementary projects. Examples include, but are not limited to human disease associations (e.g., OMIM), model organism phenotypes (e.g., IMPC, AGR), results from CRISPR screens in cells (e.g., GenomeCRISPR, CRISP-view, MaveDB). The efforts of the DRACC should not duplicate the informatics efforts of other projects funded to describe the characteristics or functions of mouse genes. In addition, it will be important for the information in the database to be accessible to other such projects.

    Serve as an administrative and coordinating center for the consortium. The DRACC will be responsible for facilitating communication and coordination within the consortium. This includes organizing and facilitating consortium meetings such as Steering Committee, working group, and annual consortium all-hands meeting, and the establishment of web conference and internal communication platforms (e.g., Wiki, Slack). The DRACC will also facilitate interactions within the consortium by supporting activities such as: joint projects and analyses, publication of consortium-wide analyses, biological sample transfers between consortium members (including material transfer agreements), development of standard operating procedures and policies, properly consenting biological samples.  Furthermore, the DRACC will track the status of experiments and data report regularly on the status of the above tracked activities to NHGRI and the consortium. 

    The DRACC will work with external consortia and programs to facilitate joint analyses, data integration, and the sharing of standards, pipelines, and best practices. Dissemination needs concerning the output of the consortium to different research communities will be assessed by the DRACC to inform promotion and outreach efforts. The DRACC will collect community input, as needed, about the consortium data resource and implement improvements based on feedback.

    The DRACC will also work with all consortium members to define broader strategies for data collection and analyses that will maximize the consortium’s overall scientific impact and contribute to the goal of accelerating understanding of gene function. Flexibility, as described earlier, will be required as aspects of the consortium's proposed studies may be adjusted to align with the goals and data collection strategy of the MorPhiC Consortium. All awardees in the MorPhiC Consortium will be expected to participate in consortium-wide, collaborative activities and analyses. The DRACC will have a key role in helping to organize and present information about consortium progress to the consortium, and to work with the consortium and NHGRI staff to summarize key scientific and technical questions and challenges that arise during the course of the work.

    Consortium Formation and Responsibilities

    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.

    Specifically, 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. For the DRACC, a key collaborative task will be to demonstrate the robustness, utility, and impact of the data in order to inform plans for a larger Phase 2.

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

    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 DPC and DAV.
    • 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. Applicants should budget adequate funds for collaborative work in all grant years.

    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.

    Considered Non-responsive

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

    • Projects that are not focused on the analysis of phenotypic consequences of null alleles in human cells or that fail to accommodate a variety of molecular and cellular datatypes.
    • Projects that only aim to accomplish a subset of the key components (e.g., only developing data handling, or only administrative coordination) rather than identifying and addressing the components as an integrated effort.
    • Proposed work that does not indicate plans to participate in consortium-wide, collaborative activities and analyses throughout the course of the project.
    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

    NHGRI intends to commit $1.5M in FY {2022} to fund {1} awards.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    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:

    •         Hispanic-serving Institutions
    •         Historically Black Colleges and Universities (HBCUs)
    •         Tribally Controlled Colleges and Universities (TCCUs)
    •         Alaska Native and Native Hawaiian Serving Institutions
    •         Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    •         Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    •         Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    •         Small Businesses
    •         For-Profit Organizations (Other than Small Businesses)

    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
    Foreign Institutions

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
    Foreign components, as defined in the NIH Grants Policy Statement, are  allowed.

    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.
    •         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:

    Colin Fletcher
    Telephone: 301-496-7531
    Email: fletcherc2@mail.nih.gov

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. with the following exceptions or additional requirements: For this specific FOA, the Research Strategy section is limited to 30 pages overall. Six sections are required, with no specific page limits for each section of the Research Strategy.

    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.  Key personnel should demonstrate strong scientific, administrative, technical, and management expertise consistent with the objectives of the DRACC. This should include experience in working in collaborative environments and coordination of large genomics data research efforts, and experience with administrative management of research and/or resource-based efforts that serve the research community. The DRACC is expected to include expertise in genomics, data curation and provenance, bioinformatics tool development, and implementation of data sharing.

    The PD(s)/PI(s) must designate a dedicated Project Manager to direct the day-to-day operations of the Coordinating Center. A PD/PI may serve as the Project Manager.

    R&R 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 3 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 1.5 calendar months annually and the other(s) should devote sufficient time to serve his/her proposed role. The appropriateness of the effort of key personnel must be justified in the budget justification.

    Budgets should include support for a dedicated Project Manager who will devote a minimum of 6 person months, based on a 12-month calendar, to oversee the day-to-day activities of the DACC, coordinate across DRACC sites, if applicable, and be responsible for promptly providing requested reporting information to NHGRI Program Staff. A PD/PI may serve as the Project Manager.

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

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

    Budget 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 2-6 members of the center to attend annual consortium meetings thereafter that start in year 1.

    Budgets should include any funds required to support sharing of genomic data under this FOA (e.g., to prepare the data for submission to appropriate repositories).

    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: 

    Specific Aims: Describe the specific goals of the DRACC and its role in achieving the overall objectives of the MorPhiC Consortium. 

    Research Strategy: In the Research Strategy, applicants should propose plans, approaches, and potential alternative strategies for carrying out the goals of the DRACC. Applications should address all the key elements in an integrated way. The Research Strategy must consist of the following subsections uploaded as a single PDF attachment:

    1) DRACC Overview and Management

    2) Receive, Wrangle, QC, and Store Data

    3) Data Analysis and Validation Centers Collaboration

    4) Analysis and Dissemination of Data

    5) Integration of Information

    6) Administrative Coordination

    Details about what should be discussed in each section are described below.

    1) DRACC Overview and Management

    • Provide an overview of the proposed DRACC and how it will be structured to achieve the center’s goals. We highly encourage that the center’s activities be divided into two components: (1) Data handling activities and (2) Administrative Coordination. Describe the management structure of the proposed DRACC, including the role of the Project Manager responsible for day-to-day operations, components of the DRACC and how they will interact to function as a cohesive center, key personnel and their responsibilities, and overall center leadership. This should include a description of how consortium activities will be managed, including interactions with other consortium centers, data wrangling, and management of any external collaborations.
    • Discuss, without duplicating information in the biosketches, past experiences (if any) in working in collaborative environments and coordination of large data research efforts, and experience with administrative management of efforts that serve the research community. Describe previous experience with a substantial number of the data types expected, including genome sequence, molecular -omics, cellular phenotypes, and imaging data.
    • Include a detailed timeline and milestones for tracking all aspects of the center and the proposed activities. Whenever feasible, milestones should provide quantitative metrics for assessing the center’s progress (e.g., expectations and timeline for development of data processing pipelines). Given these initial consortium plans, milestones will be reviewed and updated, as needed, in consultation and with the approval of NHGRI.
    • Applicants should indicate how they would work with the consortium to achieve consensus, and how they will revise their plan to take into account the consortium strategy for prioritizing genes and assays, and optimizing methods for reproducibility.
    • If there are additional responsibilities that are not detailed in the FOA but are considered necessary for effective operation of the DACC, applicants should note them in this subsection and other subsections, as appropriate, and describe potential approaches.

    2) Plans and approaches to receive, wrangle, and QC primary data, develop a database for storage, and make data available for consortium and community use.

    • Provide a description of submission processes for all consortium data, metadata, and analyses. This should include plans for working with the consortium to establish standardized formats to facilitate regular and efficient transfer of data and metadata.
    • Describe processes for accessioning and providing unique data identifiers to enable tracking and storing of data provenance, as well as plans for monitoring data quality.
    • Describe plans for development of a robust and scalable database capable of housing all data and metadata, protocols, and analyses of the consortium generated for the duration of the project period. This should include a demonstration of how computational infrastructure and personnel may be adjusted over time to meet the needs of the consortium. Applicants should demonstrate the capacity to scale activities as data volumes or complexity change within the consortium.
    • Describe strategies for transferring data to external repositories as appropriate (e.g., SRA or protocols.io).
    • Describe plans to ensure data is generated and submitted consistent with the FAIR Guiding Principles and in AI-ready formats appropriate for advanced machine learning approaches.

    3) Plans and approaches to support modeling, visualization, and validation efforts by the Data Analysis and Validation Centers.

    • Provide a description of plans for working with the Data Analysis and Validation Centers. 

    4) Plans and approaches to develop processing pipelines and a web portal to disseminate information to the biomedical research community.

    • Describe plans for implementing and running data processing pipelines, documenting pipeline descriptions and parameters, and providing access to documentation and pipeline software with versioning to the broader research community.
    • Describe plans for use of hybrid cloud opportunities, mix of publicly funded resources and commercial cloud and use of XSEDE and other similar programs for computations.
    • Describe plans to use cellular phenotype ontologies or controlled vocabularies to annotate the results of statistical analysis.
    • Describe plans to automate and scale the analysis and annotation of 2D and 3D image data.
    • Describe plans for development of a portal for accessing data and metadata. This should include a description of metadata-based query tools as well as tools for visualizing data, use of Application Programming Interfaces (APIs) or web services, and methods for downloading data from the portal. Existing software should be utilized, where applicable.
    • Describe plans to incorporate other products of the consortium components (e.g. predictive models, visualization tools, etc.).
    • Describe plans to support faceted browsing of the MorPhiC data.
    • Describe plans to evaluate usability of the portal that includes members of the consortium and outside users. This should include a description of the targeted outside user communities (e.g., computer scientists, biologists, geneticists, etc.), a description of specific use cases that will be evaluated, evaluation frequency, and how this information will be used to improve utility of the portal.
    • Applicants should also describe a plan to coordinate with NHGRI for the transfer of consortium-generated data, software, and other resources in the event the DRACC is transferred to another awardee or the Government.

    5) Plans and approaches to develop methods to integrate with similar/complementary resources.

    • Describe plans for identifying complementary information resources that would enhance the MorPhiC data catalog
    • Describe plans to implement interoperability with external datasets.
    • Describe plans for ontology matching or synonym identification in order to correlate MorPhic data with other collections.

    6) Plans and Approaches to Serve as an Administrative and Coordinating Center for the Consortium.

    • Provide strategies and approaches for enabling communication and coordination of consortium activities such as establishment of web conferencing platforms and any needed communication platforms.
    • Describe plans for facilitating interactions within the consortium and organizing consortium meetings such as working groups, Steering Committee meetings, community tutorials, and jamborees.
    • Describe plans to facilitate in-person investigator meetings. This should include descriptions of needed logistical and operational management. Include plans to incorporate innovative strategies for conversion of in-person meetings to virtual, as needed.
    • Describe strategies for tracking consortium activities, experiments, and data, and regularly reporting status to NHGRI and the consortium.
    • Provide strategies and approaches for coordinating plans for analyses and facilitating interactions with other consortia and programs.
    • Provide a strategy and plans for disseminating information and leading outreach efforts to promote consortium resources to the broader research community. This should include an overview of target audience(s) and methods (e.g., tutorials, workshops, plans for announcement via the portal and social media, and online training resources).

    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, Resource Sharing Plans are required for this FOA. Applicants must address all the points below.
    • In their Resource sharing Plans, applicants should indicate their willingness to abide by all resource sharing 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. Applicants will propose a data sharing plan consistent with this goal that addresses rapid data sharing with the community and describes plans 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. For this consortium, data will be sent initially to the DRACC. It may be required to send data to other repositories, either directly or via the DRACC. Note that, once the consortium is formed, we expect to develop cross-consortium policies for data sharing; this will be led by the DRACC.

    Selection of Biological Samples and Ability to Share Sample Data with Community: 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 is 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 must include samples or cell lines that are derived from individuals of diverse ancestry and allow for consideration of sex as a biological variable. 

    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, protocols, 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. 

    Plan for Sharing Other Resources:  NHGRI intends that, in addition to data, software, and analyses, any physical resources, such as DNA clones and cell lines, generated by awardees, should be made rapidly available to the research community and that such sharing plans should follow the same principles and spirit as data, software, and analysis release plans. The applicant should provide specific plans for resource sharing and distribution in the application. If the application will use pre-existing commercially available resources (e.g., knockout iPSC lines) the terms of availability of these lines should be described. Key factors for this are availability to the community at reasonable cost and on equal terms; and use terms with lack of reach-through with regard to claims on downstream discoveries. Applicants should also propose plans for sharing experimental protocols and methods.

    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

    N/A

    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 center contribute to understanding the effect of genetic perturbation on cellular phenotypes?

    How likely is the DRACC to generate a community resource of high utility to the broader research community?

    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 and sufficient PD(s)/PI(s) effort to serve the key proposed roles, been described?

    Have adequate plans for working collaboratively with other components of the consortium in consortium-wide activities been described?

    Do the PD(s)/PI(s) and other personnel have appropriate experience with a substantial number of the data types expected, including genome sequence, molecular -omics, cellular phenotypes, and imaging data?

    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?

    Specific to this FOA:

    Does the application propose efficient use of available tools and resources to accomplish the goals of the center? Does the application propose development of new tools and resources, if necessary?

    Does the application propose novel strategies for disseminating information and leading outreach efforts to promote consortium resources?   

    Approach

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

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

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

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

     Specific to this FOA:

    Are processes described for the submission and storage of MorPhiC Consortium data reasonable and appropriate? Does this include plans for establishing standardized formats, data quality metrics, vocabularies, and ontologies? If so, are these plans reasonable and appropriate?

    How sufficient are the plans for implementing and running data pipelines, documenting the descriptions, and providing access to these documentations and software with the broader research community?

    Are the plans for development of a database and portal, including plans for query and visualization tools, providing APIs or web services, and methods for downloading reasonable and appropriate?

    Are the plans for tracking consortium activities, experiments and data, and regularly reporting status to NHGRI and the consortium reasonable and appropriate? What is the likelihood that the proposed center can effectively track the progress of the MorPhiC Consortium's activities?

    How sufficient are the approaches for facilitating and coordinating plans for consortium-led analyses?

    Are the strategies for outreach, dissemination, and promotion of consortium resources likely to engage the broader research community?

    Are the timeline, milestones, and goals for the proposed research project clearly described, reasonable, and appropriate? 

    Are the Resource Sharing plans adequate? Do they address how the applicants will ensure rapid release of data, including metadata, in a way that will be useful to the community? Do the applicants consider the role of the Data Resource and Administrative Coordinating Center (DRACC) described in companion FOA HG-2021-31)? Have the applicants adequately considered release/availability of other products (e.g., software, cell lines) of the proposed work? Are plans for resource sharing practical within the budget limitations?  Is there a commitment to work within the MorPhiC consortium to develop and adopt policies relating to resource sharing and data quality?  

    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? 

     Specific to this FOA:

    Is the informatics infrastructure adequate to meet the needs of the consortium and are plans for adjusting this infrastructure to accommodate the needs of the consortium reasonable?    

    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

    Not Applicable

    Select Agent Research

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

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    2. Review and Selection Process

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

    As part of the scientific peer review, all applications:

    • 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 on Human Genome Research. The following will be considered in making funding decisions:

    •         Scientific and technical merit of the proposed project as determined by scientific peer review.
    •         Availability of funds.

    Relevance of the proposed project to program priorities.

    These include:

    • Program balance, meaning the need for this program to process data from multiple comparable approaches studying diverse cell and tissue types, with consideration of the diverse datatypes; and potential for synergy between MorPhiC components towards the Phase 1 goals of testing 1000 genes.
    • 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.
    • Whether analyses to be used are appropriate for samples from participants from diverse populations. Does the application, considered together with others, advance the imperative to ensure that the results are applicable across populations?
    • 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. 

    NHGR 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 NHGR 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)

    Colin Fletcher
    National Human Genome Research institute (NHGRI)
    Telephone: 301-496-7531
    Email: fletcherc2@mail.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)

    Devon Bumbray-Quarles
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-451-7928
    Email: devon.bumbray-quarles@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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