Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Current prioritization of genes for biological characterization does not necessarily reflect their physiological importance nor their 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 spectrum disorders 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 initiated and is expanding 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 expand the consortium of investigators with broad expertise in the areas of genomics, high throughput technology, and neurobiology, linked together through a central Data Resource and Administrative Coordination Center (DRACC) that serves to promote collaboration and communication and to provide data integration across the consortium.

The SSPsyGene Consortium consists of two highly interactive components with complementary roles as follows:

• Assay and Data Generation Centers (ADGCs) awarded through this NOFO and previously through RFA-MH-22-111 will engineer a selected set of comparable null and other alleles across experimental systems, 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) 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 the implementation of high- and moderate-throughput assays. Ultimately, the goal of the initiative is to broadly characterize gene function 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 initiative 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., Mus musculis, Xenopus tropicalis, Danio rerio, C. elegans)
• Others with 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 current target for the initiative is 100-250 protein-coding 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 have been established, may also be selected. Gene selection will be 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 or deeper, focused analysis of a subset of 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- and moderate-throughput methods.

As part of this goal, the overall SSPsyGene Consortium will:

• 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.
• Implement common data formats and examine the ability to use the data to address different kinds of neurobiological questions.

All of 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.

ADGC: Purpose and Scope of Activities

This NOFO seeks to expand the ADGC component of the SSPsyGene Consortium. The goal of the ADGCs is to optimize and implement scalable and systematic assays to interrogate the neurobiological functions of a common set of 100-250 NPD risk genes selected by the SSPsyGene Consortium Coordinating Committee (CCC). The ADGCs will form a collaborative network, working with the funded ADGCs and the DRACC to perform complementary assays on the selected set of genes and to develop quality control metrics and standards for methods, data and metadata to ensure results are comparable and reproducible, and to enable data integration.

Each ADGC will be responsible for targeting the common set of genes in their chosen system(s), taking advantage of existing cellular and/or model organism resources (e.g., Knockout Mouse Project, Zebrafish International Resource Center) where available.  It is expected that proposed allele generation methods and assays will be sufficiently developed to begin production-scale implementation of assays within the first year. Additional optimization of the key technical steps proposed (e.g., mutagenesis, gene dosage, model systems, or assays) for improved scale, quality, or cost is expected in coordination with the DRACC. Furthermore, applicants to this NOFO may propose optional optimization and piloting of innovative new assays for CNS profiling of gene function.

The specific objectives of the ADGC are to carry out three inter-related efforts:

1. Perform a systematic functional assessment of ~100-250 risk genes (selected by the CCC) using scalable screening platforms to assess neurobiological function. Each application must propose projects that address at least one of the following high-priority assay areas:
   • Molecular assays (e.g., epigenomic, transcriptomic, proteomic, metabolomic), including studies on interaction complexes, networks and pathways.
   • Cellular, circuit, or systems/organismal assays (e.g., signaling, synaptic activity, circuit and neural ensemble dynamics, connectivity mapping and morphology, correlation of activity with behavior).
   • Optional: Develop and optimize novel pilot assays. Projects for assay development should emphasize the design and validation of creative approaches to assay biological processes that have the potential to broadly inform our understanding of NPD risk gene function in the CNS.
2. Develop and/or implement methods to ensure comparability and reproducibility, including data metrics and quality standards and standardized allele and assay validations.
3. Actively contribute to the SSPsyGene Consortium integration efforts.

1. Carry out a systematic functional profiling of the prioritized risk genes using scalable screening platforms to assess neurobiological function.

The ADGCs will obtain or generate null or other alleles of SSPsyGene Consortium-selected NPD risk genes in their proposed experimental systems. While the initial focus is to characterize null alleles for insights into basic gene function, to address the ultimate goal of understanding the functional impact of disease-associated genetic variation, it is anticipated that assays will also include haploinsufficiency models and/or allelic series from a select subset of NPD risk genes.

The ADGCs will then conduct systematic phenotypic analysis of the alleles. Each application must propose projects that address at least one of the high priority assay areas listed below (A, B, C). Applicants have the flexibility to select one assay category or may opt to propose research projects in multiple areas. Assays should be considered based on their throughput and the utility of information they provide to advance understanding of the neurobiological function of NPD risk genes. Applications that propose to carry out multiple complementary assays within each priority area or across areas are of particular interest. Repeated measures are encouraged (when feasible) to investigate dynamic properties across temporal scales (e.g., signal propagation, cellular plasticity and key developmental epochs).

Following an agreement by the CCC on gene selection, quality control metrics and standards for methods, data and metadata, the ADGCs will submit a finalized assay implementation plan to NIMH.

1A. Molecular Assays

Assessments should focus on unbiased, comprehensive phenotyping approaches, for example via genomics (e.g., gene expression, transcriptional and translational regulation, DNA methylation, chromatin state and conformation, etc.) or other omic-scale profiling (e.g., proteomics, metabolomics). This can include analysis of protein-protein interaction complexes, networks and pathways with validation of their physiological relevance. Proposed allele generation methods and assays should be developed enough to begin production-scale work within the first year.

1B. Cellular, Circuit, or Systems/Organismal Assays

Functional analysis of the SSPsyGene Consortium-selected gene set may be performed using high-throughput assays of key neurobiological functions or processes. Assays may require some optimization but should be ready to begin to implement at scale (e.g., capable of testing alleles of 100-250 genes) within the first two years of the project. Consideration and justification should be given for assay selection based on throughput relative to the utility of physiologically relevant information they provide (e.g., cell-based versus in situ versus whole organism).

Potential assays of interest include, but are not limited to:

• Protein-level characterization of NPD risk genes to assess impact on ionic flux, electrophysiological, developmental/morphological phenotypes at cell and circuit levels (e.g., structural and biophysical properties, translational modifications, endogenous protein dynamics).
• Molecular interactions and pathways (e.g., signal transduction, neurotransmitter-receptor interactions, protein-protein interaction networks).
• Inter-cellular functional interaction (e.g., synaptic activity measures using optical physiology).
• High resolution neural activity (e.g., multi-electrode array activity profiling, calcium imaging of population dynamics, high density electrical recording in awake behaving animals).
• High content imaging assays (e.g., cellular morphology, structural plasticity).
• Assays assessing neurodevelopmental processes (e.g., proliferation, differentiation, migration, maturational timing, circuit formation).

1C. Moderate-throughput, high-content assays

While it is anticipated that assays will characterize the full set of 100-250 selected genes, some phenotypes and assay formats may be more amenable to moderate scale screening against a subset (50-100) of the gene set. Assays may require some optimization but should be ready to begin to implement at scale (e.g., capable of testing null alleles of 50-100 genes) within the first two years of the project. Assays of interest include, but are not limited to:

• Activity-based or perturbation-based assays (e.g., activity-induced synaptic plasticity, pharmacological perturbagens).
• Imaging brain activity or morphology at key developmental stages in model organisms.
• Novel assays capturing the expression or biological activity of brain signaling molecules such as proteins, lipids, transcriptional regulators, inflammatory markers.
• Scalable assays for assessing anatomic or physiological connectivity in the nervous system.
• Novel adaptation of assays to increase throughput or include high content, multiplexed measures that maximize the amount and value of the captured data.
• Novel adaptation of assays for imaging and quantifying dynamic changes in the localization of signaling molecules or intracellular compartmentalization.
• Development of assays using state-of-the-art approaches for single cell analysis to evaluate, for example, cell-type specific responses and time-dependent processes.

1D. Optional: Develop and optimize novel pilot assays.

The development of novel high-throughput phenotyping assays of high utility and rigor will be needed to enable deep functional characterization of NPD risk genes. As new knowledge is gained from ongoing SSPsyGene Consortium efforts, new phenotypes of interest may be identified. New technologies may emerge from programs like the BRAIN Initiative that would expand the screening capabilities of the SSPsyGene Consortium. To allow ADGCs to remain nimble and flexible, proposed approaches can be complemented by the adoption and optimization of new technologies and pilot assays into their pipelines. Projects for assay development should emphasize creative approaches to assay neurobiological processes that have the potential to broadly inform our understanding of NPD risk gene function in the CNS. These assays may require optimization to achieve high (100-250 genes) or moderate (50-100 genes) throughput scale with sufficient rigor and reproducibility. Pilot projects presented in the application will be reviewed as part of the assessment of scientific and technical merit of the application, and as examples of the kinds of pilot projects that the overall program might initiate in the future. Promising pilot assays may be considered for advancement to full-scale implementation as prior assays are completed. Initiation of pilot assays will require NIMH prior approval. Pilot assay development should not be the primary focus of the project. Pilot assays may not be proposed in Year 1 and may comprise no more than 10% of the budget.

2. Develop and/or implement methods to ensure comparability and reproducibility, including quality standards, standardized methods, metadata, allele and assay validation metrics.

The ADGC will:

• Work with the SSPsyGene DRACC and other members of the consortium to implement a common structured and controlled vocabulary and terminology in the domain of cell biological structure and function, which will take into account other ontological frameworks (e.g., Gene Ontology [GO], SynGO).
• Collaborate with the DRACC to develop and implement data processing pipelines for submission of data.
• Implement consortium specifications for data and metadata and data quality metrics.
• Submit all primary data, metadata, protocols, methodologies, analyses, software, and other products to the DRACC and appropriate repositories in specified formats according to an agreed-upon timeline. NIMH supports the broadest appropriate genomic data sharing with timely data release through widely accessible data repositories. Awardees are expected to comply with the NIH Data Management and Sharing Policy and, as applicable, the NIH Genomic Data Sharing Policy. 

3. Actively contribute to the SSPsyGene Consortium.

The ADGC will:

• Collaborate with the DRACC, other funded ADGCs, and external scientific consultants in the CCC to establish and update 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 subset of genes for functional characterization across the consortium.
• Participate in the development of, and follow NIH and consortium policies on Data Management and Sharing  and resource sharing.
• Take part in SSPsyGene CCC and working group meetings.
• Participate in consortium activities such as joint projects and analyses, publication of consortium-wide analyses, biological sample transfers between consortium members (including material transfer agreements), and development of standard operating procedures and policies.
• Present status updates and report regularly on the status of assay implementation and data transfers to the DRACC data repository at CCC meetings.
• Share best practices and lessons learned within the consortium and with the external community.
• Work with all consortium members to define broader strategies for data collection and analyses that will maximize the consortium's overall scientific impact and contribute to the goal of accelerating understanding of gene function.

As the first group of ADGCs have been funded for the SSPsyGene Consortium in response to RFA-MH-22-111, potential applicants are encouraged to propose experimental systems and assays not currently represented within the consortium. Applicants are encouraged to review the currently funded awards in NIH Reporter and also discuss plans with the scientific contacts below to ensure that their application is not duplicative of current efforts and enhances the existing research .

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 expanded consortium, organized by the DRACC, within 3 months of award.  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 responsible for establishing consortium policies, monitoring progress, encouraging improvements, and coordinating 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 NOFO are expected to define a clear set of overall goals that are aligned with the objectives 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, including data submission timelines, should be described. Plans should be included for critically evaluating and revising these milestones on a regular basis. The ADGCs will also participate in DRACC-led CCC meetings to define overall data production and analysis milestones that will be coordinated and established across SSPsyGene Consortium projects.

Plan for Enhancing Diverse Perspectives (PEDP)

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. 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 to optimize and implement scalable technologies to functionally characterize genes and gene variants associated with NPDs at the desired scale (e.g., 100-250 genes for high-throughput assays, 50-100 for moderate-throughput assays).
• Projects that aim to accomplish only a subset of the key components (e.g., only developing alleles, or only assays) rather than identifying and addressing all key components as an integrated effort.
• Applications that do not detail plans for collaborating with the DRACC and across the SSPsyGene Consortium, including participating in consortium meetings, data harmonization, and other collaborative activities and analyses throughout the course of the project.
• Projects that are reliant on behavioral phenotyping as the sole or principal outcome measure, and/or designed to mimic human symptoms rather than as proxies for underlying synaptic or circuit function, as described in NOT-MH-19-053.

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 NOFO. The Webinar will occur on October 26, 2023, at 2:00PM Eastern time. Further information will be posted on the event website https://www.nimh.nih.gov/news/events/announcements/the-scalable-and-systematic-neurobiology-of-psychiatric-and-neurodevelopmental-disorder-risk-genes. During the webinar, NIMH staff will present overviews of the NOFOs and answer NOFO-related questions from prospective applicants. Questions may be submitted in advance to [email protected]. 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

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

Section III. Eligibility Information

1. Eligible Applicants

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

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. 

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted 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. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

This NOFO 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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the 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: [email protected]

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 NOFO, the Research Strategy section is limited to 20 pages.

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

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

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

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

In addition, the following should be addressed in 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 historically underrepresented 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.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp 

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 PD(s)/PI(s) and key personnel to attend the initial in-person consortium kickoff meeting, and for the PD(s)/PI(s) and 2-3 members of the center to attend annual in-person consortium meetings thereafter. In all years, reasonable costs must be allocated to support consortium activities as described in the ‘Purpose and Scope of Activities’ section.

Budgets should include all funds required to support sharing of biospecimens and genomic data under this NOFO, as appropriate, in accordance with NOT-MH-21-265.

A separate budget should be provided for optional pilot assays (if proposed). Pilot assays may not be proposed in Year 1 and may comprise no more than 10% of the total budget. Funding for optional pilots is contingent on NIMH prior approval.

R&R Subaward Budget

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

PEDP implementation costs

 Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement Section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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

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

Application Instructions Applications must include all the items requested below.

Specific Aims: Describe the specific goals of the Assay and Data Generation Center (ADGC) and its role in achieving the overall objectives of the SSPsyGene Consortium.

Research Strategy: In the Research Strategy, propose plans, approaches, and potential alternative strategies for carrying out the goals of the ADGC. Applications should address all the key elements in an integrated way. The Research Strategy must consist of the following subsections:

1. Center Overview and Management
2. Genetic Modification and Experimental Assays
3. Data Management and Analysis
4. Consortium Involvement and Integration

Each section must include the details discussed below.

1) Center Overview and Management

• Provide an overview of the proposed ADGC and how it will be structured to achieve the center’s goals and the major objectives of the NOFO. This should include a high-level description of the strategic approach proposed (generation of alleles, model systems, assays), along with the high-level rationale behind those choices, with details to be covered in the subsections below. The overview should provide a sense of how the proposed effort will expand the capabilities of the SSPsygene Consortium and contribute data, methods, and knowledge to advance the understanding or interpretation of NPD gene function. Any planned technical, strategic, methodological, analytical, or other innovation may be highlighted.
• Outline the expertise of the research team (without duplicating information in the Biosketches) and explain how their expertise aligns with the key components of the NOFO.
• Describe the management structure of the proposed project, including components of the project and how they will be integrated to form a cohesive whole, key personnel and their responsibilities (such as those responsible for data collection, data analyses, and data submission), and overall project leadership.
• As part of the management plan, give an overview of how the essential elements of reproducibility will be addressed in all participating laboratories. Details about ensuring reproducibility with respect to other projects within the consortium should be included in the appropriate sections below.
• Include a detailed timeline and milestones for tracking all aspects of the project and the proposed studies. Applications to this NOFO are expected to define a clear set of overall goals that are aligned with the SSPsyGene Consortium goals and include annual milestones with metrics that will document progress towards the achievement of the overall goals. For each assay, clear, quantitative outcomes should be set and described and should include plans for critically evaluating and revising these milestones on a regular basis. Note that this is separate from decisions made across projects of the consortium, which will be described below.

2) Genetic Modification and Experimental Assays

For the elements below, describe both the individual elements and their integration. Descriptions should address how approaches have the potential to scale. Consider how the elements overall will balance throughput and interoperability/utility of the data and its relevance to human phenotypes. Describe potential problems, alternative strategies, the process for evaluating whether the element is successful (including benchmarks), and how you will respond if issues arise.

This NOFO encourages applications that propose innovative approaches to address the goals and objectives of the SSPsyGene initiative. Proposed innovations should be justified, e.g., in terms of improved methods, scalability interpretability/utility of data, and integration between key elements.

• Describe how alleles will be produced along with the rationale for this choice. Applications may propose to generate new null or other alleles, or may use existing resources (e.g., available libraries of CRISPR/Cas9 alleles in iPSCs that can be differentiated into systems for assays; knock-out animal resources such as the Knockout Mouse Project, Zebrafish International Resource Center). For null studies, proposed approaches need not be strictly limited to actual genetic knockouts, as long as the alleles are functionally equivalent to a null (i.e., do not produce functional protein) and otherwise aid in attaining the NOFO goals. Applications must describe how alleles will be ascertained/QC'd to validate the intended loss/gain of function and ensure they are stable enough to work in assays and how they will assess dosage sensitivity. Details for generating and validating an allelic series of patient variants from a subset of genes should also be provided. Include a discussion of potential artifacts or confounders (e.g., genetic compensation for certain alleles; cases in which the homozygous null is cell lethal in their assays; cases where heterozygous null effects are not detected in selected assays, degree of cross-species conservation) and how they will be addressed. Discuss willingness to adhere to consortium standards for allele QC.
• Describe and provide a detailed rationale and justification for the experimental systems (e.g., choice of species or reduced preparation, inclusion of drivers, reporters or effectors) and how they will be produced and characterized. It is important to address issues with reproducibility and biological variability, and the potential for scalability and comparability with results from other experimental systems and assays. Quality control metrics specific to the paradigm should be clearly detailed, e.g., projects involving the use of human iPSC lines should address QC guidance described in Notice of Biospecimen Sharing Policy for the National Institute of Mental Health NOT-MH-21-265. All choices should be clearly justified in terms of the NOFO goals.
• Describe and provide a detailed rationale for the proposed full-scale assays and how they will be carried out, including information about controls/comparisons. Assays should be well-justified in terms of their potential to scale and to provide useful, interpretable information related to human phenotypes. Discuss rationales for assay choice (individually and in combination). Describe current assay throughput. For assays requiring optimization, describe plans and timelines for achieving the desired throughput.

In this section include details about considerations in overall project design, including measuring or accounting for natural and technical variability, application of statistical methods (both data processing and study power), and generally how the data will be interpreted.

Optional for applications proposing pilot studies: Describe plans and rationale for development and optimization of pilot assays. The support for individual pilot project studies is typically of relatively short duration (e.g., 1-2 years), depending upon the nature of the research. Applications requesting support for pilot projects must describe a plan for setting specific milestones for evaluating pilot assay performance and incorporating assays into the project pipeline. Pilot projects presented in the application will be reviewed as part of the assessment of scientific and technical merit of the application, and as examples of the kinds of pilot projects that the overall program might initiate in the future.

3) Data Management and Analysis

• Propose data management and analysis plans including data processing, data quality assessment and quality control (QA/QC), and ensuring completeness, appropriate tracking, preservation, integration, and availability of the data, and transmission to the DRACC. For this section, please describe your laboratory information management system, how it will be implemented for this project, why it will be adequate over the life of the project, and what incremental improvements may be needed. Include a "sample/data flow" diagram illustrating the path that data generated internally will follow, from sample logging and data generation, to internal lab management systems, to analysis, and to deposition. Describe the proposed approach for coordinating with the DRACC to implement data processing pipelines. Discuss plans for collaborating with the DRACC to establish data formats and standards and for transferring, in a timely manner, data (e.g., genomic, functional, phenotypic) and metadata to the DRACC, using agreed-upon formats and processes. Applications must describe a plan for providing quarterly updates on data transfer and data quality metrics to the DRACC/CCC.
• If not already detailed in the elements above, please discuss any specialized analytical software and algorithms to be used, for example, in processing raw molecular and cellular phenotype data.
• Applicants are encouraged to identify analytical or data processing steps that are likely to represent common challenges across ADGC's, and that represent opportunities to develop solutions that are more uniform or reproducible across the consortium.
• The funding available in this NOFO for analyses is limited, so applicants should narrowly prioritize analyses that are designed to characterize the quality and utility of their data for downstream applications (e.g., consistency, biological and technical variability). Describe any software that will be used to support the analyses, if not described elsewhere. Describe and justify all proposed analyses.

4) Consortium Involvement and Integration

Discuss past experiences (if any) in working as part of interdisciplinary teams and/or large collaborative research efforts. Describe plans for maintaining a high level of consortium engagement. This can include plausible routes by which your overall plan can work in combination with those of other SSPsyGene ADGC's and the DRACC, to ultimately produce high quality, consistent data across the SSPsyGene Consortium. Although the details of the other centers cannot be known in advance, applicants should discuss the potential for their proposed assays to be used by others, for example to allow comparisons between centers. Within the context of your experimental approach, incorporate elements from the NOFO Purpose and Scope of Activities described above, including:

• Indicate your willingness to use the set of risk genes selected by SSPsygene, to collaborate with the CCC to update the common set of NPD risk genes as needed, and to identify allelic series from a subset of genes for functional characterization across the consortium.
• Developing and implementing methods to ensure data comparability and reproducibility across centers, including quality standards, standardized methods, metadata, allele, and assay validation metrics.
• Actively contributing to the SSPsyGene Consortium integration efforts.

On behalf of all collaborators on the application,  include an explicit statement in which all applicants agree to adhere to collective decisions by the consortium, as coordinated by the DRACC, relating to these elements.

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 Resource Sharing Plan.

Resource Sharing

Resources generated by the SSPsyGene Consortium projects should be made rapidly available to the research community. Applications must include a detailed plan for sharing resources and include the following key elements:

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

Resource sharing plans must be in accordance with NIH and NIMH policies, including:

• Sharing of all generated resources, including assay protocols, technology platforms, tools, reagents,  and open-source software.
• Applicants are expected to propose open dissemination of computational methods and software for unrestricted redistribution and modification. All resources 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. In post-review negotiation with NIMH, the final version of the resource sharing plan will become a term and condition of the award.
• In accordance with the Notice of Biospecimen Sharing Policy for the National Institute of Mental Health, NOT-MH-21-265, grantees who generate or use human subject-derived reprogrammed cells in their NIMH-funded research are expected to submit relevant source cells (e.g., fibroblasts, olfactory epithelial cells, blood) and reprogrammed derivatives (e.g., iPSCs) to the NIMH Repository and Genomics Resource (NRGR). Human subject consent language associated with such biomaterials and data collection should be consistent with banking and wide sharing through centralized repositories. The Resource Sharing Plan should describe biospecimen types, estimated numbers and a timeline for submitting these to NRGR.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Data and Data Analysis Sharing.

A central goal of this NOFO 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 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 assay data generated are expected to be made publicly available. Applications must include a detailed plan for sharing data and include the following key elements:

• Project management of data sharing.
• Description of what specific data will be shared (e.g., single cell omics data, immunohistochemistry data, cell morphology data, electrophysiological data).
• Schedule/timeline for availability of data to other users.

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

Applicants must provide a specific proposal to comply with NIH Data Management and Sharing Policy for data sharing in the application, and address the issues related to the public release of data and data analyses (see the rationale for FAIR (Findability, Accessibility, Interoperability, and Reusability) Data Principles). SSPsygene will implement a common data release plan that will address the interests of the data producers and analysts, as well as external users of the data. The SSPsygene data release plan will be integrated with the Data  Management and Sharing Plan and become a term and condition of the awards. Applicants should indicate their willingness to accept such a plan. The NIH expects that verified raw data will be submitted "in real time” or other agreed-upon time-frame depending on the data types and verification requirements to the SSPsyGene data archive and/or other long-term publicly accessible archives such as Gene Expression Omnibus (GEO) or others as appropriate. Agreement to abide by the data and data analysis sharing policy is a requirement of the SSPsyGene Consortium.

Following the agreed-upon SSPsyGene quality control metrics and standards for methods, and data and metadata, the ADGCs will submit a finalized assay implementation plan to NIMH. ADGCs will provide quarterly updates on data transfer and data quality metrics to the DRACC/CCC.

NIMH Data Management and Sharing Policy for Research with Human Subjects

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this Notice of Funding Opportunity (NOFO) are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). 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 NOFO 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 website 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 NOFO 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. For more guidance on submitting data to NDA, refer to the NDA: Submitting and Sharing Data. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

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

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.

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

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the 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.

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIMH, 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.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/nda/data-contribution.html#cost) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Management and Sharing for Applicants and Awardees.

Applicants are required to follow the instructions for post-submission materials, as described 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 NOFO:

• To what extent do the proposed aims and research strategy align well with the goals of SSPsyGene?
• To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance 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 NOFO:

• To what extent 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 NOFO:

• To what extent does the application propose novel approaches and methodologies that expand the capabilities of the Consortium and advance the SSPsyGene goals? 
• To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

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 NOFO:

• How well-justified are the proposed experimental elements (e.g., genetic modification, experimental paradigms, assays) ?and are plans adequate for their implementation and integration? To what extent has the application demonstrated that the approach is ready, or nearly ready, for scalable generation of high-quality data to address the SSPsyGene goals (e.g., characterization of ~100-250 genes)?
• If applicable, how well-justified are the proposed pilot assays in terms of risk/benefit, proof of concept and deliverables? Is the plan to evaluate their readiness for implementation and incorporate them into the pipeline adequate?
• How well do the plans for informatics infrastructure (e.g., data processing, handling/integration, analysis, and submission) support the proposed work?
• To what extent are the plans for quality assessment and quality control, and ensuring data reproducibility, reasonable and adequate?
• To what extent does the application provide sufficiently detailed and satisfactory plans to work with other ADGCs and participate in SSPsyGene Consortium activities, including CCC meetings, gene/allelic prioritization, standardization and harmonization of data production pipelines, and undertaking collaborative efforts?
• To what extent does the application provide sufficiently detailed and satisfactory plans for maintaining a high level of engagement with and responsiveness to the DRACC, including but not limited to adhering to regular meeting and data submission timelines?
• Are the Resource Sharing plans acceptable? To what extent do they address how the applicants will ensure rapid release/availability of generated resources (e.g., software, cell lines, model organisms) of the proposed work? Is there a commitment to work within the SSPsyGene Consortium to adopt policies relating to resource sharing?
• Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?
• How realistic and well-justified are the proposed milestones, timelines and goals proposed for the research project?

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 NOFO:

• How well does the proposed informatics infrastructure 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 Animals 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

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).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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 NOFO.

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 NOFO. 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.
• Potential for synergy between SSPsyGene components towards the goal of characterizing NPD risk genes.
• Potential to work effectively in large collaborative efforts or research consortia.
• Adequacy of Data Management and Sharing Plan 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 2.4.4 Disposition of Applications.

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.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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 will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. 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 NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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.”

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

• When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
• Awardees will provide updates at least annually on implementation of the PEDP

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

David Panchision, Ph.D.
National Institute of Mental Health (NIMH)
301-402-3969
[email protected]

Jamie Driscoll
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: [email protected]

Amanda J. Price, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-5224
Email: [email protected]

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: [email protected]

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: [email protected]

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.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.