Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)

Funding Opportunity Title
Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes: Data Resource and Administrative Coordination Center (U24 Clinical Trial Not Allowed)
Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type
New
Related Notices

  • May 9, 2022 - Notice of Availability of FAQ for RFA-MH-22-110 and RFA-MH-22-111. See Notice NOT-MH-22-240.
  • February 04, 2022 - Notice of Technical Assistance Webinar for RFA-MH-22-110 and RFA-MH-22-111. See Notice NOT-MH-22-155.

Funding Opportunity Announcement (FOA) Number
RFA-MH-22-110
Companion Funding Opportunity
RFA-MH-22-111 , RM1 Research Project with Complex Structure
Assistance Listing Number(s)
93.242
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is one of two to establish the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium. The long-term goal of SSPsyGene is to systematically characterize phenotypes, across biological scales of organization (molecular, cellular, circuit, systems/organismal), for neurodevelopmental and psychiatric disorder (NPDs) risk genes. This resource will be made available for broad use by the biomedical community.

The program will leverage scalable technologies to functionally characterize ~100-250 null alleles from genes with an increased burden of loss-of-function mutations in NPDs. It will also optimize novel assays for cellular and physiological phenotypes, assess the scale limitations of such methods for allelic series of patient variants across large numbers of risk genes, and develop common data formats.

This specific FOA seeks applications for a Data Resource and Administrative Coordination Center (DRACC) that will be responsible for (1) establishing a rigorous approach to prioritize NPD risk genes for functional characterization across the consortium, (2) providing administrative and logistical coordination among all funded groups in the consortium, (3) establishing a data processing pipeline, and (4) building and maintaining a knowledge base that adheres to Findability, Accessibility, Interoperability, and Reuse (FAIR) principles. The DRACC will work in a hub and spoke model in collaboration with the Assay and Data Generation Centers (ADGCs), as described in the companion funding announcement RFA-MH-22-111 to achieve the goals of the SSPsyGene Consortium.

Key Dates

Posted Date
January 19, 2022
Open Date (Earliest Submission Date)
May 10, 2022
Letter of Intent Due Date(s)

30 days prior to the application due date.

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
June 10, 2022 Not Applicable Not Applicable November 2022 January 2023 April 2023

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

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

Expiration Date
June 11, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Current prioritization of genes for biological characterization does not necessarily reflect their physiological importance nor relevance to human disease. Instead, 90% of research focuses on 10% of genes in the human genome. This limited knowledge base impedes our ability to understand basic gene function and disease mechanisms despite accelerated discovery of disease genes over the past decade. One of the main bottlenecks in translating disease-associated genes into biological insight lies in the lack of scalable experimental platforms that can extend the unbiased nature of gene discovery to the discovery of biological function.

Most attempts to evaluate the impact of disease-associated genes or variants have been limited in scale to one or a few genes against a relatively narrow range of biological functions. Systematic efforts are constrained by our ability to fully capture the spectrum of potential disease relevant biological phenotypes across a sufficiently large number of genes or variants in a cost-efficient and comprehensive way. New scalable technologies are emerging that address these limitations and offer the opportunity to probe the role of genetic variation in complex common diseases, such as neurodevelopmental and psychiatric disorders (NPDs; e.g., autism and schizophrenia). This can be achieved with systematic and coordinated assays that more thoroughly capture the genetic and phenotypic space at a scale and breadth not covered by existing efforts. Such an approach would provide a collaborative and efficient framework for identifying biological function beyond current small-scale and often ad hoc single gene efforts in order to generate a standardized, experimentally derived, functional catalog of NPD risk genes. This basic neurobiology resource would provide a fertile foundation for future studies into disease mechanisms.

The NIMH is thus initiating a new program, the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium, with the long-term goal of developing a comprehensive phenotypic catalog across biological scales (molecular, cellular, circuit, systems) for genes and gene variants associated with NPDs.

Consortium Structure and Objectives

The SSPsyGene Consortium will support multidisciplinary research centers to optimize and implement systematic and scalable approaches for characterizing the developmental, molecular, cellular, systems, and organismal neurobiological function of genes associated with risk for NPDs. The resulting phenotypic data will be integrated across modalities, levels of organization, and genes to create a harmonized, integrated knowledge base that forms a solid foundation of data needed to make robust inferences into potential shared and unique disease mechanisms. To accomplish this objective, NIMH intends to establish a consortium of investigators at multiple sites and with broad expertise in the areas of genomics, high throughput technology, and neurobiology, linked together through a central Data Resource and Administrative Coordination Center that serves to promote collaboration and communication and to provide data integration across the consortium.

The SSPsyGene Consortium will be comprised of:

  • Assay and Data Generation Centers (ADGC) RFA-MH-22-111 to engineer a selected set of comparable null alleles across experimental systems, to assess and catalog the resulting molecular and cellular phenotypes, pilot these assays for a select allelic series of clinically significant variants, and support optimization of innovative assays of central nervous system (CNS) function.
  • Data Resource and Administrative Coordinating Center (DRACC) RFA-MH-22-110 (this FOA) will coordinate with the ADGCs to develop a rigorous data-driven strategy for selecting a set of 100-250 NPD risk genes; receive, integrate, annotate, harmonize, and present data for consortium and public use; and provide leadership and logistical support for the consortium.

Assays will include CNS-relevant phenotypes across scales of biological organization from molecular and cellular to physiological and organismal that are amenable for scalable and systematic investigations. The initial focus for the SSPsyGene Consortium will be on implementation of high-throughput molecular and cellular assays. Ultimately, the goal of the initiative is to broadly characterize genes across a variety of fundamental CNS functions including developmental processes, cell morphology, neurite motility, intrinsic membrane properties, synaptic physiology, inter- and intra-cellular signaling, circuit dynamics, natural behaviors, or other neural phenotypes. To support this goal, the initiative will also support optimization and implementation of pilot assays using scalable screening platforms/technologies.

This initative supports the use of experimental systems – in vitro or in vivo, cellular or organismal – that are reproducible and scalable for hundreds of genes, are informative of human neurobiology, and align with NIMH priorities. Examples of potential scalable experimental systems include:

  • Human cell-based assays (e.g., induced pluripotent stem cells [iPSCs])
  • Model organism paradigms (e.g., Xenopus tropicalis, Danio rerio, C. elegans)
  • Others w/ high-throughput capabilities (e.g., ex vivo, non-human cell-based assays)

While the long-term goal of the SSPsyGene Consortium is to build a comprehensively annotated resource describing the CNS function of all NPD risk genes, the target for the initial phase of the initiative is 100-250 protein coding genes. These will be selected from genes with a genome-wide significant increased burden of mutations identified in large-scale sequencing studies of NPDs such as intellectual disability/developmental delay, autism spectrum disorder, and schizophrenia. Genes that have a demonstrated pathogenic role in rare forms of NPDs, for which penetrant rare variants have been identified and rigorous statistically significant evidence of causal roles has been established, may also be selected. The DRACC will coordinate with the ADGCs to develop a strategy to select and prioritize the set of 100-250 genes through the SSPsyGene Consortium Coordinating Committee (CCC), in accordance with the guidance provided in the Report of the National Advisory Mental Health Council Workgroup on Genomics. The number of genes selected will be sufficient to allow for a diverse set to be targeted to begin to sample the space of genetic risk and reveal potential points of biological convergence, while also permitting overlap to test the same gene in multiple assays and enable the assessment of reproducibility and robustness.It is anticipated that all assays will be conducted against the core, common set of genes, with the potential for inclusion of additional genes when warranted.

The primary goal of the SSPsyGene Consortium will be to implement available methods to assay the biological functions of the selected set of NPD risk genes across experimental systems and to characterize their neural effects using high throughput methods.

SSPsyGene will also:

  • Optimize and implement novel scalable assays that assess cellular and physiological neural function.
  • Establish the scale limitations of existing and new methods and identify technical and other bottlenecks for assessing the impact of allelic series of patient variants.
  • Develop common data formats and examine the ability to use the data to address different kinds of neurobiological questions.
  • Test the feasibility of integrating the key technical components into a production pipeline.

This will be used to assess the feasibility of potential subsequent SSPsyGene phases extending to increasingly complex circuit, systems, and behavioral scale assays of gene function. The data and analyses performed initially will substantively advance our knowledge of basic gene function and how to design large-scale, high-throughput approaches for characterizing the neurobiological function of genes.

DRACC: Purpose and Scope of Activities

This FOA seeks to establish a Data Resource and Administrative Coordinating Center (DRACC) for the SSPsyGene Consortium. The DRACC will serve to coordinate and collaborate with all Assay and Data Generation Centers (ADGCs) as the core of SSPsyGene. The DRACC will be responsible for leading the SSPsyGene Consortium Coordinating Committee (CCC) in the development of a rigorous formal framework for prioritizing risk genes and 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 and disease-associated variants. The DRACC will be expected to oversee and work closely with other consortium components to develop standardized data submission, quality metrics, and processing. The DRACC will disseminate the primary data and processed and annotated data to the research community via a web portal. In addition, the DRACC will develop methods to integrate with similar or complementary resources. Finally, the DRACC will serve as an administrative coordination center and thus will lead and support consortium interactions.

The specific objectives of the DRACC are to:

  • Establish a rigorous approach to prioritize NPD risk genes for functional characterization across the consortium.
  • Develop a comprehensive, formal neural phenotype knowledge base.
  • Receive, wrangle, and quality control (QC) primary data, develop a database for storage, and make data available for consortium and community use.
  • Serve as an administrative and coordinating center for the consortium.

Establish a rigorous approach to prioritize NPD risk genes for functional characterization across the consortium.

The DRACC will be responsible for convening the CCC, within 3 months of award, to prioritize a set of ~100-250 genes associated with NPDs for assessment within the SSPsyGene Consortium. Several criteria should be taken into account when prioritizing genes:

  • The exact number of genes selected will depend on feasibility given costs, potential assays, and the available timeframe.
  • Initial characterization efforts will focus primarily on null alleles. To maximize the potential disease relevance of null effects, genes with a genome-wide significant excess burden of loss-of-function mutations in NPDs such as intellectual disability/developmental delay, autism spectrum disorder, and schizophrenia will be the focus. The consortium will also determine the need to assess heterozygous and homozygous states, and develop a rigorous, data-informed approach for selecting patient variants to pilot assays against an allelic series from a small, select subset of NPD risk genes. The DRACC will be responsible for leading the CCC in the gene prioritization process, including engaging external scientific consultants (e.g., with statistical genetics expertise) to serve on the CCC.
  • Additional factors to consider are expression within the experimental systems, conservation across species, developmental specificity, balanced representation across disorders, existing knowledge of gene function (with less studied genes to be prioritized), and alignment with the recommendations from the Report of the National Advisory Mental Health Council Workgroup on Genomics.

Develop a comprehensive neural phenotype knowledge base.

The goal is to build a comprehensive neural phenotype knowledge base that includes data-driven phenotypic taxonomies and ontology across data modalities, biological scales, and experimental systems. Expected activities include:

  • Working with the consortium to establish a common controlled vocabulary and terminology in the domain of cell biological structure and function, which will take into account other ontological frameworks (e.g., SynGO, GO).
  • Curating and annotating genetic phenotypes with respect to their key attributes and cardinal features to characterize and display shared and distinct functional features among the genes selected for phenotyping (e.g., molecular, anatomical, and functional characteristics).
  • Linking knowledge across data modalities, species, and developmental stages, including those collected in other knowledge bases and scientific literature.
  • Develop a formal inferential framework for assessing whether any set of genes selected on some feature (e.g., disease association) share biological functions beyond an experimentally established null expectation.

Receive, wrangle, and provide quality control for primary data, develop a database for storage, and make data available for consortium and community use.

The DRACC will:

  • Develop and maintain a system for tracking of data provenance and flow from ADGC data production to submission to the DRACC, to access/sharing among consortium members, to 3rd party distribution, through to publication and end-of-grant disposition. A dashboard system should be designed to allow SSPsyGene CCC and NIMH staff to regularly track this process, benchmarked against expected submission deadlines.
  • 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.
  • Develop specifications for data and metadata in collaboration with the consortium and establish data quality metrics.
  • 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 to improve data sustainability and utility. Primary data, metadata, or protocols may be deposited in other repositories, as appropriate. The DRACC will ensure that data, metadata, and protocol archiving in outside repositories is FAIR compliant.
  • 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.
  • Provide general plans and flexible data management workflows that address the multiple potential data types and tools that may be generated by the consortium. Potential data types may include, but are not limited to sequencing data (e.g.,10X Genomics, SMART-seq, sci-RNA-seq, ATAC-seq, mC-seq, HiC, etc.); other omic-scale data types (e.g., proteomics, metabolomics); high-content imaging data (e.g., immunohistochemistry, cytoarchitecture histology, spatial transcriptomics, morphology); neural activity data (e.g., optical physiology, multi-electrode array activity profiling, calcium imaging of population dynamics); and other data types (e.g., molecular interactions and pathways; perturbation-based assays such as activity-induced plasticity or pharmacological manipulations, etc ).
  • Develop methods to ensure interoperability with similar/complementary resources (e.g., Brain Initiative Cell Census Network, PsychENCODE, NIMH National Cooperative Reprogrammed Cell Research Groups, Impact of Genomic Variation on Function (IGVF) Consortium, Knockout Mouse Project) and existing archives for long-term storage options (e.g., NIMH Data Archive, Gene Expression Omnibus). .

Provide leadership/direction and serve as 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 leading consortium meetings such as CCC (to meet monthly), working group (frequency to be determined), and consortium all-hands (to meet annually) meetings, and the establishment of web conference and internal communication platforms (e.g., Wiki, Slack).
  • Facilitating 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.
  • Tracking the status of experiments and data and reporting regularly on the status of the above tracked activities to NIMH and the consortium.
  • Working with external consortia and programs to facilitate joint analyses, data integration, and the sharing of standards, pipelines, and best practices.
  • Collecting community input, as needed, about the consortium data resource and implementing improvements based on feedback.
  • Working 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.
  • All awardees in the SSPsyGene Consortium will be expected to participate in consortium-wide, collaborative activities and analyses.

Consortium Activities

The activities described above will be coordinated by the DRACC and directed by the CCC. All investigators will attend a kickoff meeting for the consortium, organized by the DRACC, within 3 months of award. A major focus of the kickoff meeting will be establishing the consortium's gene selection strategy, and interactions within and between components. The CCC, composed of the PIs of the DRACC and funded ADGCs (as voting members) and external scientific consultants (as non-voting members) will be established to discuss and finalize the gene selection strategy, monitor progress, encourage improvements, and coordinate the production of datasets and resources. The SSPsyGene CCC members will hold monthly teleconferences and meet in-person annually to plan and design activities, review and discuss progress, and establish priorities and policies for publication. Awardees will be required to accept and implement policies approved by the CCC. Applicants should budget adequate funds for collaborative work in all grant years, including attendance at in-person CCC meetings.

Data Quality and Reproducibility

Two of the cornerstones of science advancement are rigor in designing and performing scientific research and the ability to reproduce biomedical research findings. Data reproducibility is especially important in view of the inherent biological variation and expected technical noise. The SSPsyGene Consortium will strive to quantify and benchmark biological variability throughout the data generation and analysis pipelines, and establish and disseminate data and metadata standards. Applicants are expected to develop and establish stringent data quality control and quality assurance processes to their best capabilities for data processing, assay and statistical approaches, so that the data generated will be broadly referenced and used by the research community. Such harmonized approaches are expected to enable cross-modality, cross-scale, and cross-species data integration, as well as to facilitate the analysis of variability and the transfer of information and knowledge between basic and clinical or structural and functional studies.

Milestones

Applications to this FOA are expected to define a clear set of overall goals that are aligned with the objective of SSPsyGene, and include annual milestones with metrics that will document progress towards the achievement of the overall goals. For each milestone, clear, quantitative outcomes should be set and described and should include plans for critically evaluating and revising these milestones on a regular basis. Year 1 milestones will include planning and defining SSPsyGene Consortium strategies including preliminary gene prioritization schema, data harmonization and processing. As the SSPsyGene Consortium develops, joint gene prioritization schema, overall data production and analysis milestones will be coordinated and established across SSPsyGene projects.

Plan for Enhancing Diverse Perspectives (PEDP)

This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below). Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material. Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

Non-responsive Areas of Research

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

  • Projects that do not propose plans to accommodate the anticipated variety of data types (as outlined in the ‘DRACC Purpose and Scope of Activities’ section) necessary to develop a comprehensive phenotypic catalog across biological scales for genes and gene variants associated with NPDs.
  • 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 NIMH 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 March 15, 2022 at 1:00PM Eastern time. Further information will be posted on the event registration website. During the webinar, NIMH staff will present overviews of the FOAs and answer FOA-related questions from prospective applicants. Questions may be submitted in advance to SSPsyGene@mail.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

NIMH intends to commit $1,500,000 in total costs in FY 2023 to fund 1 award.

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 5 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)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

  • 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 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.

  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
    • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
  • eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

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 instructions in 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:

Email: nimhpeerreview@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 is limited to 15 pages.

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.

Other Attachments:

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

  • Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
  • Description of any planned partnerships that may enhance geographic and regional diversity.
  • Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
  • Proposed monitoring activities to identify and measure PEDP progress benchmarks.
  • Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
  • Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
  • Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
  • Publication plan that enumerates planned manuscripts and proposed lead authorship.
  • Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.
SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Budgets should include funds for the DRACC to host the initial consortium kickoff meeting and annual consortium meetings thereafter beginning in Year 1. Funds should also be included for engaging external scientific consultants to participate in in-person and virtual consortium meetings.

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:

Application Instructions

Specific Aims: Describe the specific goals of the DRACC and its role in achieving the overall objectives of the SSPsyGene 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) Selection of Genes for Functional Characterization

3) Neural Phenotype Knowledge Base

4) Data Processing, Analysis, Integration and Management

5) Leadership of the CCC and 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 four primary objectives (see above DRACC: Purpose and Scope of Activities).
  • Describe the components and management structure of the proposed DRACC, including key personnel and their responsibilities. Describe the proposed consortium management plan, including interactions with the DRACC Steering Committee (DSC), Consortium Coordinating Committee (CCC), and the ADGCs.
  • Describe a plan for identifying and engaging external consultants with expertise in statistical genetics and development of data standards. While the qualifications and expertise of the consultants should be described, they should not be named in the application, contacted or appointed prior to review (Note: Nominations for the consultants to the DRACC will be subject to approval by the NIMH Program Officer).
  • Discuss prior experience in coordination of, and collaboration within, large data research efforts.
  • Include a detailed proposed timeline and milestones for tracking all aspects of the center and the proposed activities, including quantitative metrics whenever feasible. Milestones will be reviewed and updated, as needed, in consultation and with the approval of the NIMH Program Officer.

2) Selection of Genes for Functional Characterization

  • Describe the DRACC’s proposed approach for prioritizing a set of 100-250 NPD risk genes for characterization across the consortium. The strategies proposed by the DRACC and ADGCs will be discussed and finalized by the DRACC and the CCC after award. Address plans for the engagement of external scientific consultants (e.g., statistical genetics expertise) as needs arise to assist in the development, refinement, and finalization of gene selection within the CCC.
  • Describe a prioritization schema for choosing allelic series among a select number of genes and identifying appropriate assays to asses the series based on initial experimental results of SSPsyGene.
  • Applicants should indicate how they would work with the CCC to achieve consensus, and how they will revise their plan throughout the funding period to take into account new evidence.

3) Neural Phenotype Knowledge Base

  • Describe a strategy for establishing a common structured controlled vocabulary and terminology in the domain of cell biological structure and function, which will take into account other ontological frameworks (e.g., SynGO, GO).
  • Discuss the proposed approach for curating and annotating genetic phenotypes with respect to their key attributes in order to characterize and display shared and distinct functional features (e.g., molecular, anatomical, and functional characteristics).
  • Describe methods to link knowledge across data modalities, species, developmental stages, including those collected in other knowledge bases and the scientific literature.
  • Describe the data, metadata, and/or data processing requirements necessary to achieve a formal inferential framework for assessing whether any set of genes selected on some feature (e.g., disease association) share biological functions/annotations beyond chance based on an experimentally established null expectation.

4) 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 previous experience with expected data types (see DRACC Purpose and Scope of Activities).
  • Describe plans for monitoring data quality
  • Describe a process to enable the consortium investigators and the NIMH Program Officer to regularly access data quality and submission statistics, benchmarked against expected submission deadlines.
  • Describe plans for development of a robust, scalable, and accessible (preferably open access) database capable of housing all consortium data and metadata, protocols, and analyses 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.
  • Describe plans to ensure data is generated and submitted consistent with the FAIR Guiding Principles.
  • Describe plans and approaches to develop formal methods for integration and interoperability with similar/complementary resources. Describe strategies for transferring data to external repositories as appropriate.

5) Plans and approaches to serve in a leadership role for the CCC and as an Administrative and Coordinating Center for the Consortium.

  • Describe the plan for the DRACC to convene the initial meetings of the CCC, including external scientific consultants, which will establish a rigorous approach to select a common set of 100-250 NPD risk genes, determine the need to assess heterozygous and homozygous states, and identify an allelic series from a small subset of genes for functional characterization across the consortium.
  • Describe the plan for the DRACC to convene the CCC to develop specifications for data and metadata in collaboration with the ADGCs and establish data quality metrics.
  • Describe 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 to facilitate in-person Consortium 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.
  • Provide strategies and approaches for coordinating plans for analyses amongst Consortium members and facilitating interactions with other consortia and programs.

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan.

A central goal of this FOA is to build a comprehensive functional phenotyping data resource that will be widely used throughout the research community for further advancing research. The open sharing of the functional data, research tools, and resources will not only lead more rapidly to their broad use by the research community, but also encourage scientific rigor in data production and analysis, with resulting benefits to public health. In order to achieve the maximum value from this program, all molecular, anatomical, and physiological data, experimental protocols, and tools generated are expected to be made publicly available. Applications must include a detailed plan for sharing data and resources and include the following key elements:

  • Project management of data and resource sharing.
  • Description of what specific data and resources will be shared (e.g., single cell omics data, immunohistochemistry data, cell morphology data, electrophysiological data, software, model organisms, reagents, experimental protocols, completed tools or repurposed components).
  • Schedule/timeline for availability of data and resources to other users.

Data and Data Analysis Sharing

NIMH supports the broadest appropriate genomic data sharing with timely data release through widely accessible data repositories. If applicable, awardess are expected to comply with the NIH Genomic Data Sharing (GDS) Policy.

Applicants must provide a specific proposal for data sharing in the application, and address the issues related to the public release of data and data analyses , including, but not limited to, the timely release of open source software and data analyses including models, tools, analytic workflows, and user manuals. Applicants are expected to propose open dissemination of computational methods, software, and tools for unrestricted redistribution and modification. After all of the awards have been made, all SSPsyGene awardees will develop a final, common data and resource release plan as appropriate for the project that will address the interests of the data producers and analysts, as well as external users of the data. The final version of the resource sharing plan will become a term and condition of the award. Applicants should indicate their willingness to participate in the development of such a final plan and to accept it. The NIH expects that verified raw data will be submitted ”in real time”, or other agreed-upon timeframe depending on the data types and verification requirements, to the SSPsyGene Consortium data archive and/or other long-term publicly accessible archives such as GEO or others as appropriate. Agreement to abide by the data and data analysis sharing policy is a requirement of the SSPsyGene Consortium.

NIMH Data Sharing Policy for Research with Human Subjects

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-19-033). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this FOA are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. The NDA Data Sharing Plan is available for review on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Resource Sharing

Resources generated by SSPsyGene Consortium projects should be made rapidly available to the research community, which include:

  • Assay protocols, technology platforms, tools, reagents, and user manuals.
  • Manuscripts derived from support, in full or in part, from this award shall be submitted to an appropriate preprint server no later than the first submission to a journal for peer review.
  • Published, peer reviewed manuscripts shall include all the necessary data, code and materials to fully reproduce all findings and figures in the paper.
  • All materials shall be made publicly available by the end of the award period (including the first no cost extension) regardless of whether the findings have been published or not.

Rapid dissemination of these resources would accelerate scientific exploration and avoid duplicative resource development effort. The applicant should provide specific plans for resource sharing and distribution via repositories such as protocols.io, Addgene, GitHub, bioRxiv, or other open repositories in the application. Where applicable, plans should abide by NOT-MH-21-265: Notice of Biospecimen Sharing Policy for the National Institute of Mental Health, Including Requirements for Induced Pluripotent Stem Cell Resource Development and Sharing. In post-review negotiation with NIMH and SSPsyGene components, the final version of the resource sharing plan will become a term and condition of the award.

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.

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 fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided 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.

 

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

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 for this FOA:

  • Do the proposed aims and research strategy align well with the common goals of the SSPsyGene Consortium?
  • To what extent do the efforts described in the Plan for Enhancing Diverse Perspective further the impact of the project?

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 for this FOA:

  • Are the PD/PI and other key personnel devoting sufficient time/effort to achieve the goals?
  • To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

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 for this FOA:

  • To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to enhancing novel approaches to research?

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 for this FOA:

  • Is the proposed organizational and management structure adequate to meet the goals of the DRACC?
  • Are the timeline, milestones, and goals for the proposed research project clearly described, reasonable, and appropriate?
  • Are proposed plans for discussion and finalization of a strategy for selection of the 100-250 genes for characterization within the consortium reasonable and well-justified? Are plans for the DRACC leadership of the CCC to finalize a plan for gene selection appropriate?
  • Is the proposed approach for developing a neural phenotype knowledge base, including establishing controlled vocabularies, data annotation, and data linkage sound?
  • Are processes described for the submission and storage of SSPsyGene 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?
  • Are the plans for development of a database and portal reasonable and appropriate?
  • Are the plans for tracking consortium activities, experiments and data, and regularly reporting status to NIMH Program Officer and the consortium partners reasonable and appropriate?
  • Are the plans for facilitating and coordinating consortium activities and analyses sufficient?
  • Are the Resource Sharing plans (including Data Sharing, Model Organism, and Genomic Data Sharing (GDS), as applicable) acceptable? Do they address how the applicants will ensure rapid release of data, including metadata, in a way that will be useful to the community and according to FAIR principles? Have the applicants adequately considered release/availability of other products of the proposed work? Is there a commitment to work within the SSPsyGene consortium to develop and adopt policies relating to resource sharing and data quality?
  • Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspective well-developed and feasible?

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 for 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 program reasonable?
  • To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project.

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 NIMH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

Appeals of initial peer review will not be accepted for applications submitted in response to this 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 Mental Health Council. 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.
  • Program balance, including the need for this program to process data from multiple comparable approaches with consideration of the diverse datatypes.
  • Potential for synergy between SSPsyGene components towards the goal of characterizing 100-250 genes.
  • Potential to work effectively in large collaborative efforts or research consortia.
  • Adequacy of data sharing, software and analysis sharing and resource sharing plans.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this 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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 Parts 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

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

The PD(s)/PI(s) will have the primary responsibilities as described below:

  • Define the details for the project within the guidelines of this FOA.
  • Oversee and perform scientific activities.
  • Administratively manage the grant.
  • Participate as a voting member of the DRACC Steering Committee (DSC), along with NIH Program staff (as described below in Areas of Joint Responsibility).
  • Nominate 3-5 experts (e.g., in statistical genetics, data standards) that are not involved in the U24, to participate as consultants and members of the DSC, as needed, to provide advice and guidance to the DRACC. Nominations will be subject to approval by the NIH Program Officer.
  • Accept close coordination, cooperation, and participation of the NIH Project Scientist in the scientific, technical, and administrative management of the SSPsyGene DSC.
  • Provide leadership and coordination of the SSPsyGene Consortium Coordinating Committee (CCC). Serve as a voting member of the SSPsyGene CCC. Coordinate and attend monthly teleconferences and an annual in-person meeting with the SSPsyGene CCC. The PD/PI will be responsible for preparing an agenda prior to the meeting and concise proceedings or minutes of any key discussion points or action items. The DRACC PD/PI(s) will be responsible for identifying experts that are not involved in the U24 or RM1 awards, to participate as consultants and non-voting members of the SSPsyGene CCC, as needed, to provide advice and guidance to the CCC.
  • Accept and implement the common guidelines and procedures approved by the SSPsyGene CCC.
  • Provide updated milestones to the NIMH Program Officer (usually at the outset of the award and annually thereafter).
  • Develop and use harmonized data standards to generate and integrate the data, metadata, and knowledge.
  • Ensure that the products of the effort meet quality standards.
  • Share data and resources according to the data release and resource sharing policies developed for and by this project as appropriate and consistent with achieving the goals of the program.
  • Adhere 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, NIMH, and the consortium.
  • Fully disclose algorithms, software source code to the other members of the consortium for the purpose of scientific evaluation.
  • Not disclose confidential information obtained from other members of the consortium outside of the consortium.
  • Participate in SSPsyGene Consortium activities, including periodic meetings to report the project progress, and coordinate publication of research results through preprint archives and journals.
  • Submit periodic progress reports as agreed upon by the SSPsyGene CCC.
  • Provide updates at least annually on the implementation of the PEDP.

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

The NIH Program Officer will:

  • Be responsible for the normal scientific and programmatic stewardship of the award, including programmatic monitoring of the overall project.
  • Be responsible for negotiating, monitoring, and implementing the data and research resource sharing plans to ensure that the goals of the project are being met.
  • Monitor the conduct and progress of the project to ensure milestones (go/no go and annual milestones) are accomplished in accordance with the timeline.
  • Approve modifications to the research plan in consultation with the DRACC Steering Committee, based on emerging data and/or other issues that impact progress of the project.
  • Monitor performance and compliance with NIH procedures.
  • Negotiate the data types and frequency of new data collection by the DRACC, quality control, and cost goals with the recipients, including options to modify protocols for data collection when certain objectives of this FOA are not being met or as scientific goals evolve.
  • Participate in DSC, working group and/or special committee meetings and conference calls as a non-voting member and serve as an administrative liaison.
  • Review and approve policies on DRACC activities developed by the CCC.

The NIH Project Scientist(s) will:

  • Provide relevant scientific expertise to the SSPsyGene DRACC.
  • Participate as a voting member of the DSC and assist in developing operating guidelines for the DRACC. Participate with other DSC members in the group process of setting research priorities (key questions) for aggregation and harmonization of data, annual milestones for the project, and periodic adjustments of research approaches as warranted. If more than one Project Scientist is assigned to the U24, they will have one combined vote in the DSC.
  • Observe the SSPsyGene Consortium Coordinating Committee (CCC) meetings.
  • Assist with coordination of DRACC activities including the development of evolving tools and technologies in data science, database management, and analysis, to meet the scientific mission and evolving goals of the NIMH.
  • Assist in promoting and encouraging the sharing of unique research resources for functional phenotyping of neuropsychiatric risk genes by the scientific community at large.
  • Assist in developing timetables for the timely, open, and free sharing of data and research resources received by the DRACC to the scientific community.
  • Participate in the project update meetings and conference calls with the PD(s)/PI(s) on a weekly or monthly basis, as dictated by the needs of the project.

Areas of Joint Responsibility include:

SSPsyGene DRACC Steering Committee:

The DRACC Steering Committee (DSC) will be composed of the PD(s)/PI(s) of the U24, key personnel of the U24, assigned NIH Project Scientist(s) and external consultants (e.g., with expertise in statistical genetics, data standards, etc.). The DSC will be established to help monitor progress, encourage improvements, and coordinate the processing and integration of functional datasets and resources generated by the SSPsyGene Consortium. The DSC members will meet periodically to discuss progress in data aggregation and harmonization and establish priorities and policies. The frequency of meetings will be determined jointly with NIH program staff. Once assembled, it is expected that most decisions of the DSC will be reached by consensus. If a vote is needed, each non-NIH member of the DSC will be allowed one vote, and the NIH Project Scientist(s) will collectively be allowed one vote. External consultants will provide input but will not participate in voting. When a vote is necessary, a simple majority will be sufficient for approval.

The NIH Program Officer will attend DSC meetings as a non-voting participant.

Dispute Resolution for the U24 award:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D, and DHHS regulation 45 CFR Part 16.

The NIH reserves the right to phase out or curtail the collaborative project, or an individual component, in the event of (a) failure to complete milestones as mutually agreed upon with program staff (b) substantial shortfall in consortium participation and collaboration with other recipients, (c) substantive changes in the agreed-upon approaches with which NIH cannot concur, or (d) results that substantially diminish the scientific value of study continuation.

3. Reporting

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

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

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

Alexander Arguello, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3547
Email: alexander.arguello@nih.gov

Rebecca Beer, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-3969
Email: Rebecca.beer@nih.gov

Peer Review Contact(s)

Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov

Financial/Grants Management Contact(s)

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: weissh@mail.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 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.

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