Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI

National Cancer Institute (NCI)

Funding Opportunity Title

Technology Development for Single-Molecule Protein Sequencing and Single-Cell Proteome Analysis (R01 Clinical Trial not allowed)

Activity Code

R01 Research Project Grant

Announcement Type

New

Related Notices
  • November 18, 2022 - Notice of Early Expiration of RFA-HG-21-001, Technology Development for Single-Molecule Protein Sequencing (R01 Clinical Trial Not Allowed)" & RFA-HG-21-002, Technology Development for Single-Molecule Protein Sequencing (R21 Clinical Trial Not Allowed)". See Notice NOT-HG-23-013.
  • NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
  • October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
  • September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
  • August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
  • August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
  • April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
  • August 19, 2021 - Notice of Correction to the Open Date (Earliest Submission Date) of PAR-21-247, Technology Development for Single-Molecule Protein Sequencing (R43/R44 Clinical Trial not allowed) . See Notice NOT-HG-21-042.
  • August 18, 2021 - Notice of Correction to the Open Date (Earliest Submission Date) of PAR-21-247, Technology Development for Single-Molecule Protein Sequencing (R43/R44 Clinical Trial not allowed) . See Notice NOT-HG-21-043.
Funding Opportunity Announcement (FOA) Number

RFA-HG-21-001

Companion Funding Opportunity

RFA-HG-21-002 - Technology Development for Single-Molecule Protein Sequencing (R21 Clinical Trial not allowed)
PAR-21-247 - Technology Development for Single-Molecule Protein Sequencing (R43/R44 Clinical Trial Not Allowed)

Assistance Listing Number(s)

93.172

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits grant applications to catalyze major advances in single-molecule protein sequencing and single cell proteome analysis through technology development. The goal of this initiative is to achieve technological advances over the next five years that enable generation of protein sequencing data at sufficient scale, speed, cost and accuracy to use routinely in studies of genome biology and function, and in biomedical and clinical research in general.

Key Dates
Posted Date

July 9, 2021

Open Date (Earliest Submission Date)

New Date September 1, 2021 per issuance of NOT-HG-21-042(Original Open Date: October 1, 2021)

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

October 1, 2021; June 15, 2022; June 15, 2023

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s)

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2022; October/November 2022; October/November 2023

Advisory Council Review

May 2022; February 2023; February 2024

Earliest Start Date

August 2022; May 2023; May 2024

Expiration Date

New Date December 1, 2022 per issuance of NOT-HG-23-013. (Original Expiration Date: June 16, 2023)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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


Table of Contents

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

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


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) solicits R01 grant applications to accelerate innovation and early development in the emerging field of single-molecule protein sequencing (SMPS) and/or single-cell proteome analysis (SCPA). This FOA is seeking novel technologies or significant improvements to existing technologies. The short-term goal of this initiative is technological improvements that lead to a significant increase in one or more combinations of throughput, cost, accuracy, sensitivity, dynamic range, and scale. The long-term goal is to achieve technological advances that enable generation of protein sequencing data at sufficient scale, speed, cost and accuracy to use routinely in studies of genome biology and function, and in biomedical and clinical research in general.

Background

Modern next-generation nucleic acid sequencing (NGS) has transformed the field of genomics and biomedicine due to its high throughput, low cost, and generalizability, and has enabled many clinical applications and research projects that are producing striking insights into biology and disease. Proteomics has not had the same success or widespread adoption, partly because of a lack of proteomics technologies that have sufficient sensitivity and dynamic range for protein detection. Also, the human proteome is extremely complex. The 20 amino acid building blocks of proteins and their modifications convey a great array of chemical diversity. The size of any given proteome is a matter of debate. For pathogens, the range varies depending on genome size and pathogen lifestyle. For humans, it theoretically ranges from about 20,000 (a single representative protein for every gene) to several million when factoring in combinations of DNA-, RNA- and posttranslational modification (PTM)-level variations (proteoforms). Not all genes and their gene-product combinations are expressed in a given cell, however. In humans, it is estimated that about half of human genes (10,000) are expressed as proteins at over 20 copies per cell in a typical cell type, and proteins per cell may range from 1,000-15,000 depending on cell type and cell cycle stage. In addition, the dynamic range of proteins within a human cell can vary over 7 to 10 orders of magnitude. These factors compound the technological challenges to comprehensively characterize a given proteome.

Currently, approaches to measuring proteins on a large scale have their limitations with respect to proteome-wide detection, such as the dynamic range and sensitivity needed to routinely detect low-abundance proteins. To achieve proteome-scale capability, there is a need to significantly improve current technologies and/or develop new proteomics methods. One emerging approach, as an example, is single-molecule protein sequencing (SMPS), which is based on reading amino acid sequence from individual protein or peptide molecules.

NIH strongly encourages all investigators with innovative ideas aligned with the goals of this FOA to submit applications. NIH especially encourages applicants who are early-stage investigators, and investigators from groups that are underrepresented in the biomedical sciences, as described in NOT-OD-20-031. This underrepresentation includes women at the faculty level. Applicants to this FOA can also apply to one or more of the companion FOAs.

Objectives

This FOA seeks to fund technology development research efforts in device innovation, and sample preparation/processing approaches for single-molecule protein sequencing (SMPS) and/or single-cell proteome analysis (SCPA). The technology development proposed should have the potential to significantly propel the field of SMPS and/or SCPA forward in the next five years, and have the potential to have a large impact on future studies of genome biology or genome function. The proposed research also must have the clear potential to scale proteome wide. The technology proposed can innovate substantially novel approaches or significantly improve existing methodologies for SMPS and/or SCPA. Applications proposing innovations that provide mere incremental improvements to existing technologies will are not considered appropriate for this FOA. The FOA deliberately does not specify cost, quality, scale, sensitivity, dynamic range, throughput, or other key metrics since achievable endpoints are likely to improve during the course of this initiative and can substantially differ from one technology to another. However, the applicant must propose quantitative metrics so progress can be evaluated, and have convincing rationale that the proposed technology has the potential to scale long term and to achieve a throughput compatible with widespread adoption by the proteogenomics, biomedical and clinical research community.

Given the complexity of a given proteome, as noted above, for the purposes of this FOA, potential to scale proteome wide can be defined in the context of the specific technology and applications being proposed, and will depend on the chosen species, cell type, sample amount, as well as breadth vs. depth. Applicants may choose to work with any species and cell types, but the resulting technological advancements must be applicable to protein sequencing/quantitation in human cells, to increase our understanding of basic biological processes related to human health and disease. Additionally, this FOA encourages technological advancements that enable identification and quantification of multiple PTMs and/or provide sequence context of the PTMs. Further, the proposed technology should have the potential to go beyond a particular disease, PTM type, or cell/tissue type chosen for study and be more broadly applicable to the research community.

It is expected that applicants will develop and detail scientific and practical definitions of optimal throughput, cost, accuracy, sensitivity, dynamic range, and scale. Applicants are expected to propose significant innovations or improvements, based on state-of-the-art at the time the application is submitted. Such improvements may be achieved by focusing on one critical factor, or a combination of important ones to develop complete systems or novel key components for SMPS and/or SCPA. While this opportunity is intended to focus on amino acid sequencing approaches, this FOA is open to nucleic acid readouts as a proxy for protein sequencing (i.e., reverse-translation technology that turns peptide sequences into DNA). Research primarily focused on computational approaches (such as data analysis/modeling of complex data sets, understanding error in assigning amino acid position or side-chain identity or inferring proteins from cellular mRNA levels) is not appropriate for this FOA. However, the proposed technology developments may frequently be paired with computational approaches, such as computational tools for analysis of the new or improved data types generated to maximize usefulness and derive new knowledge. Thus, the computational tool developments that enable SMPS and/or SPCA must be integral to the proposed analysis or sequencing platform(s) being developed.

Examples of possible research topics include, but are not limited to:

  • Device, methodology and technology developments (e.g. massively parallel sequencing, nanopore, fluorescence, tunneling currents) to enable single-molecule readouts at amino acid resolution either as complete systems or components of complete systems;
  • Device, methodology and technology developments (e.g. mass spectrometry) to quantify thousands of proteins and proteoforms across many thousands of single cells;
  • Advanced microfluidics to allow interfacing of heterogeneous, low-abundance samples to single molecule sequencers;
  • Development of novel chemistries, reagents or dyes for capturing molecules, differentiating amino acids, identifying PTMs, or providing sequence context of PTMs;
  • Engineering molecular or solid-state nanopores for protein sequencing;
  • Development of nucleic acid readouts as a proxy for protein sequencing if readouts are at true single-molecule level (i.e. reverse-translation technology that turns peptide sequences into DNA).

The NCI may consider funding of R01 applications developing SMPS and/or SCPA technologies for mass spectrometry-based and affinity-based technologies if they can identify and quantify at least 1000 unique proteins per cell at once and also detect proteoforms and PTMs, and if they have utility for protein discovery in basic research and/or clinical translation in cancer.

Examples of technologies that are of interest to NCI include, but are not limited to:

  • Next generation mass spectrometry-based technologies;
  • Massively parallel sequencing by Edman degradation;
  • Nanopore sequencing;
  • Arrays of affinity reagents (such as, but not limited to, aptamers, single domain antibodies, yeast or phage displayed specific nanobodies, ligands or synbodies, biosensors).

It is important to emphasize that the activities listed above are only meant to be illustrative, and not meant to be a comprehensive list of acceptable technologies. Applications may propose technologies that are highly innovative or that are enhancements to current approaches. In either case, the proposed technologies must significantly advance the current state of the art of SMPS and/or SCPA. In order to benchmark the technology against existing approaches, applicants should provide their technology performance targets such as throughput, required sample amount, number of proteins and/or protein post translational modifications (PTMs) identified, quantified, and/or sequenced.

Applications Not Responsive to this FOA

In summary, applications that would not be considered responsive include:

  • Applications that do not address potential of the proposed technology to scale proteome-wide;
  • Applications that do not propose significant improvements to existing technologies in one or more critical factors (throughput, cost, accuracy, sensitivity, dynamic range, and scale);
  • Applications primarily focused on computational approaches;
  • For NHGRI only, applications focused on SPCA or mass spectrometry technology development.

If applicable, awardees are expected to comply with the NIH Genomic Data Sharing (GDS) Policy. More information on this expectation can be found in Resource Sharing Plan section.

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

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

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 FOA.

Clinical Trial?

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

Issuing IC and partner components intend to commit an estimated total of $20,000,000 to fund 8-10 awards. NHGRI will commit $14,000,000, and NCI will commit $6,000,000.

Award Budget

An applicant may request direct costs of up to $500,000 per year. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 3 years.

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

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.

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information
1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Tina Gatlin, Ph.D.
Email: gatlincl@nih.gov

Page Limitations

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

Instructions for Application Submission

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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 and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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

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

Research Strategy: Applicants should provide an overview of the technology being proposed and clearly specify whether the research strategy aims to improve existing or develop novel SMPS and/or SCPA technology. The relationship to existing technologies should be described, including the opportunity for significant improvement in one or more critical factors of throughput, cost, accuracy, sensitivity, dynamic range and scale. Scientific and practical definitions of these critical factors should be described. The specific metrics being proposed for significant improvement should be specified, as well as robust plans for validating and achieving them. Also, the applicant should clearly state how the technology development proposed has the potential to significantly propel the field of SMPS forward in the next five to seven years, and has the potential to have a large impact on future studies of genome biology or genome function. Applicants should also describe how they are defining proteome wide, and how the proposed technology has the potential to scale proteome wide. This potential needs to be demonstrated at some level during the course of the project.

The research plan should include a description of the level of risk of key technical challenges and alternative approaches. The research plan should clearly describe strategies to manage the inherent risk, for example, by a firm theoretical basis, supportive preliminary data, incorporating key project decision points, determining resource re-allocation, project re-direction, track record of the lead investigators acting as a team, and an outstanding scientific and management plan.

It should also include a detailed timeline accompanied by quantitative milestones that address the key scientific and technical challenges central to the approach. Timelines and quantitative milestones are essential for development of a realistic research strategy; they provide a basis for project leaders to make decisions, assess their own progress, set priorities, and redistribute resources when needed. It is particularly important to establish quantitative milestones in cases where subsequent steps in technology development depend upon threshold performance characteristics of earlier developments.

If an internal advisory board is planned, its role in managing project decision points and resource allocation should also be described. However, advisors should not be recruited or named in the application to avoid potential conflicts in the review process.

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

To accelerate progress in the fields SMPS and SCPA technology development technology development, grantees will be required to participate actively and openly in one meeting per year convened by NHGRI in coordination with NCI. Substantial information sharing will be required as appropriate and consistent with achieving the goals of the program and is a condition of the award; failure to openly share information may be grounds for discontinuation of funding. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants mustdescribe their plans for participating in the meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these meetings. Agreement to share information substantially will be a prerequisite to participation by other investigators.

Applicants are expected to describe their plan for providing access to the technology developed under this grant support, and information about that technology, consistent with achieving the goals of this program. For example, the technology might be made available as a fee-for-service, through sale of instruments and/or reagents, through collaboration, through publication and posting of results, plans and methods, or by other means. If any quantity of data will be collected under grant support, it is expected that a plan to disseminate those data will be described, consistent with achieving the goals of this program.

If applicable, awardees are expected to comply with the NIH Genomic Data Sharing (GDS) Policy. NHGRI supports the broadest appropriate genomic data sharing with timely data release through widely accessible data repositories. More information on this expectation can be found on NHGRI s Genomic Data Sharing Policy FAQs webpage and information on NCI-funded research falling under the GDS policy can be found on NCI's webpage about the Genomic Data Sharing (GDS) policy. If applicable, GDS should be addressed in the Resource Sharing Plan. In addition, NCI awardees will be expected to adhere to the general proteomic data sharing principles established such as in the Amsterdam Principles for mass spectrometry (https://proteomics.cancer.gov/data-portal/about/data-use-agreement) or an equivalent for other technologies/platforms, with timely data release through widely accessible data repositories such as NCI's cancer research data commons.

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

PHS Assignment Request Form

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

Foreign Institutions

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Non-responsive criteria are listed within Part 2, Section I, Funding Opportunity Description under a sub-heading called Applications Not Responsive to this FOA".

Post Submission Materials

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

In addition, a progress update may be submitted, limited to one printed page:

- The update is limited to new data supporting the original aims.

- Additional or updated aims, or tasks cannot be proposed with the update.

- The update must be transmitted as a PDF file, by the Authorized Organization Representative (AOR) of the applicant organization, by e-mail to the Peer Review Contact listed below.

- The update must be transmitted at least 45 days before the peer review meeting (check your NIH Commons page for the assigned peer review date).

- Any other post-submission materials are due 30 days before the meeting, according to policy.

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

Section V. Application Review Information
1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Do the methods propose new approaches or significant improvements to existing methods, as opposed to work that represents incremental improvements to existing methods?

Does the proposed research have potential to significantly propel the SMPS field forward in a five-year timeframe?

Does the proposed research have the potential to influence future studies of genome biology or genome function, or biomedical research in general?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

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

Does the research plan include scientific and practical definitions of optimal throughput, cost, accuracy, sensitivity, dynamic range, and scale; and does the approach allow for a roadmap to achieve the proposed innovations or significant improvements, in one or more of these critical factors in order to develop complete systems or novel key components for SMPS and/or SCPA?

Are the proposed innovations or improvements in these critical factors well developed and well informed, relative to the state of the technology? Is there a robust plan for validating the resulting determinations?

Are highly innovative or high-risk plans counterbalanced to manage the inherent risk, for example by firm theoretical basis, reasonable preliminary data, the track record of the lead investigators, and an outstanding scientific and management plan?

Are key technical challenges and their dependencies identified? Does the applicant adequately address the level of risk of key technical challenges, alternative approaches, go/no-go decision points? Are the applicant's plans to manage risk by managing key project decision points, determining resource re-allocation, project re-direction, etc. well described?

Are timeline and milestones included, and are they logical and realistic in addressing the key scientific and technical challenges central to the approach?

Are plans to participate actively and openly in annual meetings sufficiently clear and forthcoming so as to contribute substantially to advancement of the field?

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?

Environment

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

Additional Review Criteria

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

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.

Renewals

Not applicable.

Revisions

Not applicable.

Additional Review Considerations

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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

Applications from Foreign Organizations

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.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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 (GDS).

Examples of resources to share could include, but are not limited to: protocols and methodologies; tools; model organisms; metadata; human specimens and cell lines.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned 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 submitted in response to this FOA. 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.
  • Programmatic balance, including a diversity of experimental, throughput, scale, and computational approaches.
  • Adequacy of data sharing and resource sharing plans.
  • Expansion of the SMPS and/or SCPA community to include early-stage investigators, and investigators from groups that are underrepresented in the biomedical sciences.
3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information
1. Award Notices

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

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

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

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

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

After the initial NIH peer review of a grant application, NIH program staff will conduct an additional administrative review of the Genomic Data Sharing Plan (if applicable) and may negotiate modifications with the prospective awardee to ensure it is consistent with the principles stated above. The final negotiated version of the Genomic Data Sharing Plan will become a term and condition of the award of this FOA per the NIH GDS Policy.

The grantees will have the primary responsibility for sharing research results according to the NIH Genomic Data Sharing Policy, NHGRI-specific data sharing expectations, or NCI data sharing expectations as described in section IV "Resource Sharing Plan", and any other data sharing policy or plan agreed to between the NIH and the applicant.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

Data Management and Sharing

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

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

3. Reporting

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

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

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)

Tina Gatlin, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-2280
Email: gatlincl@nih.gov

Proposal for Translational Research

Miguel R. Ossandon, Ph.D.

Division of Cancer Treatment and Diagnosis

National Cancer Institute (NCI)

Telephone: 240-276-5714

Email: ossandom@mail.nih.gov

Proposal for Basic Research

Anowarul Amin, Ph.D.
Division of Cancer Biology

National Cancer Institute (NCI)

Phone: (240) 276-5745

Email: anowarul.amin@nih.gov

Peer Review Contact(s)

Rudy Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8739
Email: pozzattr@exchange.nih.gov

Financial/Grants Management Contact(s)

Anneliese Galczynski
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-4935
Email: anneliese.galczynski@nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

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