Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Background and Rationale

Recent advances in human genetics are reshaping the way we understand schizophrenia and other mental disorders. For example, we now have several significant genetic signals associated with schizophrenia, bipolar disorder, and autism spectrum disorder. Many of the genetic signals contributing to disease risk are enriched in non-coding regulatory regions of the human genome.

Large-scale efforts, such as the Encyclopedia of DNA Elements (ENCODE) Project, the Roadmap Epigenome Mapping Consortium (REMC), and the International Human Epigenome Consortium (IHEC) provide evidence that active regulatory regions and non-coding transcripts are often cell- and tissue-specific. However, the majority of these findings are based on cell lines or peripheral tissues. The lack of data from human brain tissue limits our insight into the molecular mechanisms underlying brain function in the context of psychiatric disorders. In particular, there are little or no data regarding network regulation of transcripts across developmental time periods and across multiple brain regions in psychiatric disorders.

Psychiatric disorders such as schizophrenia and autism spectrum disorder are generally thought to result from dysfunction of neuronal circuitry involving multiple cortical and subcortical regions with disparate temporal, spatial and cell-type specific etiologies. Therefore, to gain insights into the molecular mechanisms underlying psychiatric disorders, it is critical to generate, integrate and analyze data from multiple sets of comprehensive molecular profiles across brain areas and cell types in diseased and healthy control brains. In addition, integrative multi-level analyses of multi-modal data containing distinct biological information may facilitate identification and prioritization of potential genetic targets for drug discovery for these psychiatric disorders.

Research Objectives and Scope

The goal of this limited competition is to generate, integrate, and analyze multi-modal molecular profiles (e.g., genomic, transcriptomic, epigenomic, proteomic, etc.) from multiple brain regions and cell types/subtypes in healthy and diseased human brains. Generation of multi-omic profiles will allow direct integration of genome-wide information across multiple molecular scales for a given cell-type or brain region, or developmental period controlling for major confounds. Such integrated multi-omic molecular datasets should be leveraged to build robust and informative molecular models of disease through approaches that gain systems-level understanding of molecular interactions underlying complex genetic etiology of psychiatric disorders. These datasets will facilitate evaluation of novel brain tissue-specific exons, splicing variations, transcript and protein isoforms, RNA editing, gene regulatory elements, and epigenetic markings. Integration of these multi-modal molecular maps with other large-scale, ongoing genomic studies (e.g, Brainspan, 1000 Genomes, CommonMind, GENCODE, REMC, IHEC, Psychiatric Genomic Consortium, and GTEx) will allow researchers to use molecular phenotypes to address compelling scientific questions regarding the molecular mechanisms associated with psychiatric disorders.

This limited competition is open to the Common Mind Consortium and the PsychENCODE Consortium investigators who, by virtue of their consortia involvement, have access to existing large, high quality, phenotypically well-characterized human brain collections.  More importantly, the consortium members will be able to build upon existing data generation efforts within the consortia, leveraging data coordination and analytic infrastructure that has already been established.  For more information about eligibility, see Section III.

The collective goals of these consortia are to map the landscape of human brain-specific, genomic regulatory elements and identify their role in brain function and dysfunction in psychiatric disorders. Thus far, analyses in these consortia have been limited to RNA-Seq (transcriptome) and Chip-Seq analyses on fewer brain regions (primarily prefrontal cortex) to map functional regulatory elements. This FOA seeks to expand upon the ongoing efforts in these consortia and solicits applications to conduct comprehensive assessments of multi-omic molecular profiles across brain regions and cell-types using state-of-the-art, unbiased genomic, and computational approaches. Comprehensive assessments could include generating, integrating, and analyzing different types of omic data (e.g., genomic, transcriptomic, epigenomic, proteomic, epitranscriptomic, chromatin architecture, etc.) in healthy and diseased brains from the same cohort of brain collections that are currently being assessed by the consortia, covering two or more psychiatric phenotypes. The scope of the projects should be complementary to, rather than duplicative of, those currently supported by the consortia.

Applicants are strongly encouraged to include: 1) assessments of at least two key developmental time periods relevant to psychiatric and neurodevelopmental disorders, such as mid-fetal gestation, postnatal, early childhood, adolescence age groups, and 2) assessments of different cell types/subtypes (e.g., different neuronal and glial cell types) or cell lineages across multiple brain regions which are of relevance to psychiatric disorders. Brain regions of interest for such analyses (where data is currently limited) include nucleus accumbens, caudate-putamen, striatum, hippocampus, amygdala, thalamus, neuromodulatory regions, anterior singulate cortex, subgenual cingulate cortex, etc. Building a knowledge base of multiple domains of molecular information on a given set of samples/individuals with spatial and temporal resolution would allow discovery of regulatory mechanisms and molecular networks that drive critical neurobiological processes involved in brain development and function, as well as dysfunction, in psychiatric disorders.

All applications supported under this FOA and the companion FOA are expected to leverage existing large well-curated human brain collections represented in the PsychENCODE Consortium, the Common Mind Consortium to generate multi-omic molecular profiles in healthy and diseased brain samples. Applications are expected to also include a comprehensive plan for rapid and timely release of resulting data to the wider scientific community through existing public data repositories, consistent with achieving the goals of this program.

This FOA focuses on generating multi-omic data from across brain regions, cell subtypes, and key developmental time periods relevant to psychiatric disorders. Areas of interest include, but are not limited to:

• Generation of high-depth, whole genome sequencing data to allow for improved evaluation of various genetic alterations (e.g., single nucleotide variants, copy number variants, structural variants, etc.).
• Generation of comprehensive, high resolution human brain region/cell type and age-specific maps of different classes of functional RNA molecules (e.g., long non-coding RNAs, microRNAs, coding regions, etc.), DNA methylation, chromatin accessibility and regulatory elements (e.g., promoters, enhancers, silencers, insulators, transcription factor binding sites, etc.).
• Identification of human brain region/cell type and age-specific splicing, exon/intron junctions, transcript and protein isoforms, allele-specific expression, quantitative trait loci, mitochondrial DNA variations that are differentially represented in diseased brains compared to healthy control brains to identify epigenomic and transcriptional regulatory mechanisms that are relevant to neuropsychiatric disorders.
• Generation of human brain region/cell type and age-specific map of RNA modifications (e.g., differential distribution and frequency of RNA editing sites) in diseased and healthy control brains.
• Generation of brain region/cell type-specific proteome data from at least two brain regions in diseased and healthy control brains.
• Generation of comprehensive brain region/cell type and age-specific genome-wide maps of chromatin states, chromatin conformation, and chromatin interactions that connect genes and transcriptional regulatory regions affecting down-stream gene expression in the context of psychiatric disorders.
• Integration of these newly generated multi-omic datasets, from diseased and healthy control brains, with large-scale genomic resources such as Brainspan, 1000 Genomes, CommonMind, GENCODE, REMC, IHEC, Psychiatric Genomic Consortium, and GTEx for the identification of cell-type and age-specific gene regulatory mechanisms and molecular networks associated with psychiatric disorders.
• Development of comprehensive molecular models of disease using systems biology approaches.

This FOA should be used when two or more collaborating sites are essential to complete the proposed research.

Applicants are encouraged to consult with the Scientific/Research Contact well in advance of the application due date, to discuss the structure of the collaborations, and research topics of interest for alignment of their proposed work with the NIMH Program and FOA objectives.

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

This FOA is limited to the awardees of the PsychENCODE Consortium and Common Mind Consortium

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date revisionis not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

Eligibility for this FOA is limited to the Common Mind Consortium and the PsychENCODE Consortium investigators who, by virtue of their consortia involvement, have access to existing large, high quality, phenotypically well-characterized human brain collections.  A Program Director/Principal Investigator (PD/PI) for this FOA is limited to current PD(s)/PI(s)s, whether on a single or multiple-PD/PI grant, under the PsychENCODE Consortia supported studies; or a  Common Mind ConsortiumLeader.  However, the PD(s)/PI(s)(s) may collaborate with investigators outside of these two consortia on the projects submitted under this FOA.

This FOA supports collaborative R01 applications. Multiple PDs/PIs are allowed on any single application, however; because the collaborative R01 mechanism already supports a team approach between groups of experts across collaborating (linked) applications, the designation of multiple PDs/PIs on a single application may be less likely to apply.  PDs/PIs from each linked application should NOT be designated as multiple PDs/PIs on each application of a collaborative set.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

NIMH Referral Office at [email protected]

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

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

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

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative R01s, the titles for each R01 in the set must have the following format: a 1/N indicator + Identical title (e.g., 1/6-Multisite Comparison of Drug A vs. Drug B for Treatment of Disorder X , where the 1/6 means this is site 1 of 6 sites in the set. The other sites will be labeled 2/6, 3/6, etc.). Titles may not exceed 200 characters in length, including the tag, e.g., 1/6, at the beginning of the title.

Cover Letter Attachment: The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative R01s being submitted, including for each: 1) the PD/PI name(s), 2) the Title (including the tag, e.g., 1/6 ), and 3) the Applicant Institution. Each site should submit an identical listing.

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

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

Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section should address not only physical resources, but also the intellectual and collaborative resources for executing the project. Instructions for this section include the following:

Describe how the scientific environment in which the research will be done (e.g., institutional support, physical resources, and intellectual rapport) contributes to the probability of success of the proposed study.

Other Attachments: Linked applications must provide a single pdf attachment identical across linked application that includes the following information:

Project Management Plan Section must include the following: 1) justification for a collaborative multi-site project with a detailed description of how different elements of the project would operate in a synergistic and integrated manner; 2) description of leadership structure, overall managerial and administrative responsibilities; 3) a plan for data coordination across linked applications; 4) description of how individual sites of a linked application will coordinate on specialized subcomponents of the research project; 5) a plan for establishing cross-site comparability of assays, protocols and analytical platforms, and quality control metrics; and 6) describe processes for: joint decision-making regarding research activities; authorship rights for publications; and arbitrating and resolving disagreements and grievances.

Milestones and Timelines Section must include well described, specific, measurable, and scientifically justified milestones and benchmarks.  Milestones may include the following: tissue procurement and processing; generation of multi-omic molecular datasets, integration and analyses of multi-modal datasets for identification and comparisons of molecular signatures in diseased and healthy brains.  The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project and should not be just a restatement of the specific aims

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

It is expected that the projects will include synergistic and collaborative research teams comprised of outstanding scientists from diverse scientific disciplines with expertise in genetics, neurodevelopment, neurobiology, psychiatry, computational and bioinformatics methodologies, analysis of genome-wide data, protein biochemistry and/or other fields relevant to the FOA, as well as expertise in understanding the complexities of psychiatric genomics.

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.

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

Specific Aims: The Specific Aims must include an Overview section that describes: 1) an overall rationale for applying as a collaborative study; 2) outline the role of each site and how they will contribute to achieve the FOA objectives; and 3) Specific Aims of the collaborative project.

This Specific Aims attachment must be identical in each of the applications that are linked together in a collaborative R01 set.

Research Strategy: Applications from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration.

The Research Strategy must be identical across linked collaborative R01 applications with the exception of the section under the header "Elements Unique to This Site." All variations between sites, no matter how minor, should be highlighted; however, this section is estimated to occupy no more than 1 page of the Research Strategy Section. This subsection should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc. Any site that contracts out some portions of their work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose and oversight of this contractual arrangement.

Applications must conform with current guidelines taking care to address important elements related to Significance, Approach, and Innovation. As a part of the Research Strategy section, applicants are requested to clearly address the following aspects:

• Describe the status of current research efforts, and/or how the research proposed addresses the objectives of the FOA to build upon existing efforts of PsychENCODE Consortium and Common Mind Consortium.
• Propose the use of phenotypically well-characterized, high quality human brain samples from a large cohort of patient populations represented in the PsychENCODE Consortium and Common Mind Consortium postmortem brain collections.
• Include assessments of: 1) at least two key developmental time periods relevant to psychiatric and neurodevelopmental disorders, such as mid-fetal gestation, postnatal, early childhood, adolescence age groups, and 2) different cell types/subtypes (e.g., different neuronal and glial cell types) or cell lineages across multiple brain regions which are of relevance to psychiatric disorders.
• Focus their analyses on brain regions where data is currently limited, such as nucleus accumbens, caudate-putamen, striatum, hippocampus, amygdala, thalamus, neuromodulatory regions, cerebellum, subgenual cingulate cortex, etc.
• Propose use of unbiased molecular approaches and state-of-the-art technologies using appropriate cells or tissues derived from healthy and diseased brains to correlate findings with the pathophysiology of psychiatric disorders.  Such technologies and methods should be scalable, robust, well-validated cost effective, and high-throughput.
• Propose generation of comprehensive, high-resolution, multi-omic molecular datasets (e.g., genomic, transcriptomic, epigenomic, proteomic, epitranscriptomic, chromatin architecture etc.) in the same set of subjects (diseased and healthy control brains) covering two or more psychiatric disorders.
• Propose the use of samples from across brain regions, and cell types and cell subtypes collected from a variety of key developmental time points relevant to psychiatric disorders (e.g., mid-fetal gestation, infancy and early childhood, and adolescence).
• Provide a rationale for the choice of cell-types, brain regions, and number of samples, technologies, data collection, and validation strategies.
• Include utilization of a sufficient number of patient-derived samples to achieve appropriate statistical power.
• Describe plans for adopting and following, whenever possible, standards and protocols established by ENCODE, Roadmap Epigenome Mapping Consortium (REMC), and the International Human Epigenome Consortia. Standard ontologies should be used for experimental metadata and other data whenever possible (seehttp://www.bioontology.org).
• Provide justification for proposed DNA/RNA sequencing read length, and read depth and dynamic range for protein expression to detect and catalogue a full spectrum of genomic, transcriptomic, epigenomic and proteomic variations in healthy and diseased brains.
• Include cutting-edge computational and bioinformatics approaches for data processing, quality control, data integration and multi-level analyses of diverse data types to build comprehensive molecular models of psychiatric phenotypes.
• Propose robust plans for accurate annotation of DNA/RNA sequence to distinguish between sequencing errors and real polymorphisms.
• Describe the capabilities for data production and storage.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All applicants should provide a comprehensive plan for rapid and timely release of all raw and processed data (e.g., molecular and phenotypic data) and accompanying metadata, biomaterials, and tools to the wider scientific community through public data repositories such as database of Genotypes and Phenotypes (dbGaP), in accordance with NIH data and resource sharing policies and consistent with achieving the goals of this program.  Per NIMH policy (NOT-MH-13-002), awardees who generate or use human subject-derived reprogrammed cells are expected to submit relevant source cells (e.g., fibroblasts, olfactory epithelial cells, blood) and reprogrammed derivatives (e.g., induced pluripotent stem cells/iPSCs or other renewable cell lines) to the NIMH Genetics Resource and Repository.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIMH, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

NIH encourages 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.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the project address an important problem or a critical barrier to progress in the field? 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? Does the application address the goals and objectives outlined in the FOA which include exploring and establishing a comprehensive landscape of multi-modal molecular alterations across brain regions of patients with psychiatric disorders and developing molecular models of those disorders? Are the plans sufficiently bold to constitute a substantial advance in the ability to generate, integrate, and analyze multi-modal molecular datasets (e.g., genomic, transcriptomic, epigenomic, proteomic, epitranscriptomic, chromatin architecture etc.) to build comprehensive molecular models to provide transformative insights into the molecular networks and complex pathways that confer susceptibility to psychiatric illnesses?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Do the PD(s)/PI(s) and other key personnel have adequate expertise in genetics, neurodevelopment, neurobiology, psychiatry, computational and bioinformatics methodologies, analysis of genome-wide data, protein biochemistry and/or other fields relevant to the FOA, as well as expertise and understanding of the complexities of psychiatric genomics? Do the PD(s)/PI(s) have prior experience with coordinating collaborative research? Is there complementary and synergistic expertise across the sites? Will the leadership plan optimize the management of a milestone-driven, multidisciplinary project?

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? Is the application proposing innovative ways to lay the foundation for generation, integration and analysis of multi-modal datasets to build comprehensive molecular models of the disease to gain understanding of the mechanisms driving neurobiological processes underlying psychiatric phenotypes?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?  Does the project propose to leverage existing high quality brain collections with well-characterized psychiatric phenotypes? Does the application propose to build upon existing efforts of Common Mind Consortium and the PsychENCODE Consortium to generate high-resolution multi-omic molecular datasets for different brain regions in healthy and diseased brains? Does the proposed project include use of tissues, regions, and cell types and cell subtypes collected from a variety of key developmental time points relevant to psychiatric disorders (e.g., mid-fetal gestation, infancy and early childhood, and adolescence)? Does the project adequately address issues of statistical power? Does the project include cutting-edge unbiased genomic and computational approaches for data processing, quality control and integration and multi-level analyses of diverse data types to build comprehensive molecular models of psychiatric phenotypes? Does the project use high quality datasets for the proposed analyses?  Does the application propose adequate and robust plans for accurate annotation of DNA/RNA sequence to minimize false positives? Does the application utilize robust, well-validated cost effective, scalable and high-throughput techniques and methods? Does the proposed project address DNA/RNA sequencing read length and read depth, and dynamic range for protein expression to detect and catalogue full spectrum of genomic, transcriptomic, epigenomic and proteomic variations in healthy and diseased brains? Does the application describe plans for adopting and following, whenever possible, standards and protocols established by ENCODE, Roadmap Epigenome Mapping Consortium (REMC), and the International Human Epigenome Consortium? Are key technical barriers and dependencies identified?

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 children, justified in terms of the scientific goals and research strategy proposed?

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? Does the scientific environment (e.g., institutional support, physical resources, and intellectual rapport) contribute to the probability of success for the proposed project?

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.

Project Management Plan

Does the project describe the need for a collaborative multi-site effort using this FOA? Are sufficient mechanisms in place for different elements of the project to operate in a synergistic and integrated manner? Does the application description address data coordination across linked applications? Does the project describe how any specialized subcomponents present in this and other linked applications, will be coordinated? Does the application provide a description of the leadership structure across the linked applications? Are there adequate plans for establishing cross-site comparability of assays, protocols and analytical platforms, and quality control metrics for linked applications? Does the application describe processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievances?

Milestones and Timelines

Does the project propose realistic timelines and milestones?  Do the Milestones include the following: tissue procurement and processing; generation of multi-omic molecular datasets, integration of multi-modal datasets; and integrative multi-level analyses for identification and comparisons of full spectrum of molecular signatures in diseased and healthy brains?

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

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

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:

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory 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.

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. 

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

Projects awarded under this FOA and the companion FOA will be governed by the PsychENCODE Consortium Executive Committee to facilitate coordination of the new projects with the ongoing efforts within the Consortium.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: [email protected]

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

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.