Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Office of The Director, National Institutes of Health (OD)

National Human Genome Research Institute (NHGRI)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

Funding Opportunity Title
Omics Phenotypes Related to Down Syndrome for the INCLUDE Project (X01 Clinical Trial Not Allowed)
Activity Code

X01 Resource Access Award

Announcement Type
New
Related Notices
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Funding Opportunity Number (FON)
PAR-24-081
Companion Funding Opportunity
None
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.865, 93.172, 93.121, 93.173
Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) invites applications to submit samples to NIH INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE)-supported resources to generate a large volume of integrated genomic and multi-omics data that will facilitate discovery of the molecular mechanisms of health conditions related to Down syndrome. The resulting data, and associated clinical and phenotypic data, will become part of the INCLUDE Data Hub for sharing with the research community. No funding will be provided directly to applicants under this NOFO. Applicants are encouraged to propose omics assays of existing biospecimens collected from individuals with Down syndrome and controls. The program will accept applications that propose whole genome sequencing, including both short-read and long-read, exome, epigenome, and transcriptome sequencing, as well as proteomic, metabolomic, and single-cell RNA sequencing and ATAC sequencing, when justified. Applicants are encouraged to propose cohorts of underrepresented racial and ethnic groups or to increase racial and ethnic representation of existing collections.

Key Dates

Posted Date
December 05, 2023
Open Date (Earliest Submission Date)
February 13, 2024
Letter of Intent Due Date(s)

30 days prior to application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
March 13, 2024 March 13, 2024 Not Applicable May 2024 October 2024 December 2024
March 13, 2025 March 13, 2025 Not Applicable May 2025 October 2025 December 2025
March 13, 2026 March 13, 2026 Not Applicable May 2026 October 2026 December 2026

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

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

Expiration Date
March 14, 2026
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the 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.

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Down syndrome (DS) is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years. Despite this increase in lifespan, individuals with Down syndrome and their families face significant health challenges with age, and they have often been excluded from participation in research that could improve their health outcomes and quality of life. While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists.

Down syndrome is associated with an increased prevalence of autism and epilepsy. About 75% of individuals experience cognitive decline in a syndrome that resembles Alzheimer s disease but has its onset a decade or two earlier than typical Alzheimer s disease. Individuals with Down syndrome also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risks and resiliencies will inform medical advances for individuals with Down syndrome, and for individuals who do not have Down syndrome but share these co-occurring conditions.

This Notice of Funding Opportunity (NOFO) is one of several trans-NIH research initiatives created in response to Fiscal Year 2018, 2019, 2020, 2021, 2022, and 2023 Omnibus Appropriations Reports, which encourage NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population, while increasing the number of Down syndrome investigators and the diversity of study populations and researchers. Together, the initiatives are called the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information about projects that were funded in prior years, as well as the NIH INCLUDE Down Syndrome Research Plan, are available on the INCLUDE Project website at https://www.nih.gov/include-project/. The INCLUDE Project has three components:

  • Component 1: Targeted high risk - high reward basic science studies in areas highly relevant to Down syndrome
  • Component 2: Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions
  • Component 3: Inclusive clinical trials of existing and future treatments and interventions for co-occurring conditions in individuals with Down syndrome

Types of Research Projects

The INCLUDE Project seeks applications with biospecimen collections ready for shipping to INCLUDE data generation providers, as soon as possible after the application due date of this NOFO. In general, applications may aim to discover influential genetic variants or other risk factors underlying their targeted disorder using various study designs (e.g., trio-based, family-based, or other). An integrative omics approach may also be taken. This NOFO offers a protocol of sequencing the whole genome from high quality genomic DNA by one of the INCLUDE Project s sequencing centers, as well as protocols for exome, epigenome, and transcriptome sequencing, as well as proteomic, metabolomic, and single-cell RNA sequencing and ATAC sequencing (if available and justified). As sequencing technologies are constantly evolving, additional or alternative approaches may be proposed. For example, applicants may propose long-read sequencing approaches based on evidence of structural variation from previous short-read sequencing and analysis. The project design will be finalized in discussions among the X01 investigators, the sequencing centers, the INCLUDE Data Coordinating Center (DCC), and NIH program staff.

Specific Requirements and Expectations for this Opportunity

The cohorts selected under this NOFO must have already extracted samples or samples that are ready to be extracted. Participants must have given consent to allow broad sharing and use of de-identified individual-level sequence and associated clinical and phenotypic data through dbGaP or other NIH-approved repositories. Unless otherwise prohibited, de-identified clinical and phenotypic data will be openly shared through the INCLUDE Data Hub. Consent groups and/or data use limitations for proposed samples should be indicated on the submitted Institutional Certification using the current NIH template. Cohort samples that have consents that allow for broad data sharing and use, to include combining and comparing datasets across disease areas, (i.e., for General Research Use) are of higher priority.

No funds will be provided through this opportunity for collecting samples, performing additional phenotyping, acquiring other data types, obtaining new consent for existing samples, or performing data analysis. However, other INCLUDE initiatives may provide support for these activities. Cohorts that have provided consent to be re-contacted for additional studies are therefore encouraged.

Cohorts proposed for sequencing must include a minimum amount of associated clinical and phenotypic data sufficient to enable association analysis or omics integration analysis. Applications with rich clinical and phenotypic data that can be shared to facilitate cross-disease research among different DS co-occurring conditions will be prioritized.

Cohorts of underrepresented racial and ethnic groups or that add diversity to the INCLUDE Project datasets are encouraged.

Projects selected under this NOFO will be expected to work in a collaborative manner with designated INCLUDE sequencing center(s). Cohorts that have samples ready to ship to sequencing center(s) will be prioritized. The sequencing centers will produce requested omics data where applicable. Some applicants may wish to further collaborate with the sequencing centers for custom analysis or validation of variants for a subset of cases. Such scientific collaboration will be arranged between the applicant and sequencing center staff with oversight from the NIH, however such services may reduce the total number of samples that can be sequenced.

Data from the studies selected under this NOFO will be submitted to the INCLUDE DCC. All INCLUDE data will be processed, harmonized, and made accessible through the cloud-based infrastructure of the INCLUDE Data Hub, where investigators are encouraged to interact with the data.

PDs/PIs of selected cohort projects will participate in a collaborative effort to inform the development of the integrated data resource to maximize its impact on the research community.

Investigators selected for this opportunity will be notified by the NIH INCLUDE Project staff with the estimated number of samples approved for sequencing. Approval to access the sequencing capacity is conditional on the submission of a completed Institutional Certification covering all samples to be submitted for sequencing. If the document does not meet the INCLUDE Project s expectation for broad data sharing (i.e., General Research Use), another cohort with broader sharing may be selected instead. After approval, investigators will work with the NIH and the designated sequencing center to determine the final number of samples to be sequenced, as well as which sequencing technologies will be used. Details of sample and shipping requirements (amount, concentration, quality) will be provided to investigators.

Pre-Application Webinar

The INCLUDE Project staff intends to hold a Pre-Application Webinar for all interested prospective applicants. Webinar date and other details will be posted on the INCLUDE website: https://www.nih.gov/include-project/events.

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

Section II. Award Information

Funding Instrument

Other: A mechanism that is not a grant or cooperative agreement. Examples include access to research resources or pre-applications.

Application Types Allowed
New
Resubmission

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

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

Not applicable; there are no funds associated with a resource access award.

Award Budget

Not applicable; there are no funds associated with a resource access award.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 1 year. Investigators are expected to ship samples to designated INCLUDE Project sequencing centers within 6 months of the award notification. This period may be extended only in exceptional cases upon justification and approval.

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

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

  • 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 Organizations)
Foreign Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

  • 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 registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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 NIH Grants Policy Statement Section 1.2 Definition of Terms.

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:

Huiqing Li, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov

Page Limitations

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

  • For this specific NOFO, the Research Strategy section is limited to 6 pages.
Instructions for Application Submission

The following section supplements the instructions found in the How to Apply Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

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

Total Federal Funds Requested: Enter $0.
Total Federal & Non-Federal Funds: $0.
Estimated Program Income: Enter 0.

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: The application must include the following attachments.

1) Institutional Certification for Genomic Data Sharing:

Provide the Institutional Certification(s) using the current NIH template (https://osp.od.nih.gov/scientific-sharing/institutional-certifications/) to demonstrate that it is permissible to share individual-level genomic data to be generated for all samples proposed, consistent with achieving the goals of the program. Institutional Certifications specify the data use limitations and data use limitation modifiers, as determined by the institution's IRB (or equivalent body) after reviewing the informed consent agreed to by the participants. If the Institutional Certification is not available, provide a Provisional Certification and describe the anticipated data use limitations and associated modifiers separately. If submitting a Provisional Certification with the application, please note that a completed Institutional Certification will be required before a final selection can be made. For guidance on obtaining an Institutional Certification, see: https://commonfund.nih.gov/kidsfirst/FAQ.

2) Sample Information:

  • Describe the characteristics and number of specimens proposed for omics assays in computer readable table format.
  • Describe the number of specimens currently ready to ship to a sequencing center, and those that could be shipped at a later date in the same fiscal year (please provide a timeline if all proposed samples are not currently ready for shipment).
  • Provide a detailed inventory of the sources of the samples: number of samples from blood, saliva or buccal swab and number of samples from frozen tissue versus embedded tissue (including fixation method). DNA or other material from patient-derived cell lines will not be accepted due to the possible introduction of mutations that could confound the identification of disease-causing rare variants. Additionally, DNA or RNA from samples that have undergone decalcification will not be accepted.
  • Describe the status of the samples that will be provided, including the extraction methods used for each source and the approximate concentrations. Address their quantity and quality in terms of suitability for omics assays proposed. Describe the quality metric and method of quantification used.
  • For applications proposing chromatin accessibility assays, such as ATAC-seq, describe the tissue source and material that will be provided.

3) Clinical, Phenotypic, and Demographic Data: Describe what clinical, phenotypic, and demographic information was collected from all study participants and what is available for submission to the INCLUDE Data Hub to be shared with the wider research community. At a minimum, the following data elements are expected:

  • sex,
  • race,
  • ethnicity,
  • age at enrollment and/or age at diagnosis,
  • diagnosis (e.g., type of Down syndrome: Trisomy21, mosaic Down syndrome, translocation Down syndrome, etc.),
  • phenotypes for affected cases (list all variables collected, including co-occurring conditions),
  • phenotypes for unaffected family members (list all variables collected),
  • vital status,
  • age at last known vital status,
  • clinical information (list all available clinical data elements),
  • family medical history (e.g., family history of Down syndrome).

Describe whether electronic health records may be available for additional data extraction.
For an example template of clinical and phenotypic data elements, visit, https://commonfund.nih.gov/kidsfirst/FAQ
If appropriate, describe any available environmental or exposure data.

If a proposed cohort is selected, a data dictionary or additional data elements may be requested.

4) Family Structure (if applicable)
If proposing a non-trio design, provide any additional information that will help explain the family structures for your proposed cohort (e.g., pedigrees). Convey the total number of affected and unaffected family members proposed for sequencing.

SF424(R&R) Senior/Key Person Profile

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: The Specific Aims should refer directly to the goals of this Notice of Funding Opportunity.

Research Strategy: Research teams who have previously been approved to have cohorts sequenced through INCLUDE may submit a new application, provided that the required elements, described below, are addressed in the application. In addition, these applicants must provide scientific justification for why further sequencing should be supported (e.g., analysis of a different subpopulation, analysis of racial or ethnic groups, the addition of long read sequencing to confirm suspected structural variants, the addition of epigenomic or protein profiling), and demonstration of what progress, if any, has been made on analyzing the data from the previously submitted cohort.

Applicants are strongly encouraged to address all the following points in their application:

1) Study Population: Clearly describe the study population. Include detailed information about how subjects were identified and sampled and the method(s) of phenotypic characterization. If the subjects provided for this study are a subset of a family population, explain which individuals were included and how they were selected. Highlight special features of the study population that would enhance success. Describe the ancestry, if known, of the individuals whose samples will be submitted for genome sequencing and how this information will factor into the design of the study. Describe how the study design will be likely to lead to discovery of variants contributing to your phenotype of interest.

2) Data Analysis: Provide a plan for analyzing the data to be generated under this NOFO (note that no funds are provided under this NOFO to support analysis or other activities). Include methods for variant filtering and follow up. If there is a plan to analyze the data obtained with retrospective data. Describe why the number of samples proposed for sequencing as well as the associated clinical and phenotypic data are adequate to draw reliable conclusions about the contribution of genetic or other alterations to the condition. Use power analyses to describe the range of effect sizes detectable by the study. If RNA sequencing is proposed for affected tissue, describe how the results will be analyzed to better understand key biological and clinical characteristics of the co-occurring condition under study.

3) Contribution to the INCLUDE Data Hub and value to the DS research community: Describe how the overall study design, sample size, available clinical and phenotypic, and the sequence data to be generated will contribute to the INCLUDE Data Hub and empower research and collaborations among the DS research community. Describe a willingness to contribute secondary results to the Data Hub, upon acceptance of publication of associated findings.

4) Consent and Data Sharing: Confirm the consent used to obtain the samples allows sharing of de-identified individual level sequence data through a controlled access, NIH-approved repository such as INCLUDE Data Hub (https://portal.includedcc.org/login?redirect_path=/dashboard) and allows for sharing of the associated clinical and phenotypic data. Describe whether the consents allow for broad use of the data, including combining and comparing datasets of various disease phenotypes. Include information such as ability to recontact participants for additional phenotyping or collection of additional samples. If submitting a provisional certification because the full Institutional Certification is not available, describe the anticipated data use limitations based on the consent.

5) Accessing INCLUDE Data: Investigators are encouraged to use the cloud-based infrastructure of the INCLUDE Data Hub, wherever possible; however, if the investigative team intends to download the data to an institutional computing environment, describe how the data and security will be managed.

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.

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:

  • A Data Management and Sharing Plan is not applicable for this NOFO.

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

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

Foreign Organizations

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

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

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

4. Submission Dates and Times

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

In order to expedite review, applicants are requested to notify the NHGRI Scientific Review Office by email at barbara.thomas@nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Following initial peer review recommended applications will receive additional review by the INCLUDE Project and other NIH staff involved in the INCLUDE Project. The following will be considered:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Relevance of the proposed project to program priorities.
  • Value of incorporating the dataset into the INCLUDE Data Hub to empower research among the DS research community.
  • Compliance with resource sharing policies as appropriate and ability to broadly share and use data from the cohort in line with the goals of the program (i.e. combining and cross-analyzing genomic datasets). INCLUDE program staff reserves the right to not include cohorts that cannot be broadly shared or cross-analyzed with other INCLUDE datasets.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular NOFO, note the following:

The X01 Resource Access Program invites eligible institutions to seek access to NIH research resources, which are specified in each X01 NOFO. This includes programs where institutions will request access to submit to the resource (e.g., high throughput screening assays) as well as programs where access to a specific NIH research resource is needed to conduct certain research. Important factors in the peer review of X01 applications are the need for, and potential benefit of, gaining access to the resource, specifications for any assays proposed, timelines for completion and plans for follow-on studies.

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.


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

Specific to this NOFO:

In addition,

  • Is the trait under study significant to human health and/or the understanding of biology?
  • Is there strong evidence for a genetic component? Are the proposed studies likely to provide important new information about genetic modifiers/risk factors that contribute to DS co-occurring conditions? Is the cohort likely to strengthen the impact of the INCLUDE Data Hub and empower research and collaborations among the DS research community? Is there an ability to re-contact participants for additional phenotyping or collection of additional samples?
  • Is there additional information (e.g., environmental exposure data) that is likely to add value for further studies?

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?


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?


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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

  • Does the proposed cohort consist of highly informative cases? Are the specific phenotypic measures appropriately chosen and carefully determined? Is the depth of available clinical and phenotypic data sufficient to support the analysis plan and overall genetic discovery? Is the study design appropriate for the study?
  • Are the omics assays requested appropriate for the questions posed? In the context of other data available through the INCLUDE Data Hub, is the cohort likely to reveal previously unknown variants associated with DS and its co-occurring conditions?
  • If the applicants have previously been approved to have cohorts sequenced by INCLUDE, is there compelling justification for why further sequencing should be supported? Have the applicants demonstrated what progress, if any, has been made on analyzing the data from the previously submitted cohort?
  • 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?
  • Does the proposal include an Institutional Certification which indicates the data use limitations and/or modifiers stating how individual level sequence data can be shared with and used by secondary users, consistent with the terms of the NIH Genomic Sharing policy, https://sharing.nih.gov/?

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

Additional Review Criteria

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


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.



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.


Not Applicable.


Not Applicable.


For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.


Not Applicable


Not Applicable

Additional Review Considerations

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


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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.


Not Applicable.


Not Applicable.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHGRI, in accordance with NIH peer review policies and practices, 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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

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.

An X01 does not result in a Notice of Award (NoA). Rather, selected applicants will receive access to resources described in this NOFO. Successful applicants will receive instructions for next steps.

2. Administrative and National Policy Requirements

An X01 does not result in a Notice of Award. Instead, successful applicants will receive instructions on accessing the resources described in this NOFO.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 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

Not applicable. An X01 does not results in a Notice of Award. Instead, successful applicants will receive instructions on accessing the resources described in this NOFO.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Finding Help Online: 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

The primary point of contact for this NOFO should be:

Huiqing Li, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov

Jyoti Dayal
NHGRI - NATIONAL HUMAN GENOME RESEARCH INSTITUTE
Phone: 301.480.2307
E-mail: jyotig@nhgri.nih.gov



Kelly King, Au.D., Ph.D.
NIDCD - NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Phone: 301-402-3458
E-mail: kingke@mail.nih.gov



Sujata Bardhan, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-0471
Email: sujata.bardhan@nih.gov

Jason Wan, PhD
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: (301) 594-9898
E-mail: jasonwan@mail.nih.gov



Peer Review Contact(s)

Barbara Thomas, PhD
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8837
Email: barbara.thomas@nih.gov

Financial/Grants Management Contact(s)

Not Applicable

Deanna L Ingersoll
NHGRI - NATIONAL HUMAN GENOME RESEARCH INSTITUTE
Phone: 301-435-7858
E-mail: deanna.ingersoll@nih.gov



Christopher Myers
NIDCD - NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Phone: (301) 435-0713
E-mail: myersc@nih.gov



Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov



Diana Rutberg, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: (301) 594-4798
E-mail: dr258t@nih.gov



Section VIII. Other Information

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

Authority and Regulations

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

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