Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Office of Strategic Coordination (Common Fund)

This FOA is a Common Fund initiative through the NIH Office of the Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/). The FOA will be administered by a trans-NIH team led by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Funding Opportunity Title
Limited Competition: Genome Sequencing Center for the Gabriella Miller Kids First Pediatric Research Program (U24 Clinical Trial Not Allowed)
Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type
Reissue of RFA-RM-18-030
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-RM-21-013
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.310
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to renew the Genome Sequencing Center(s) for the Gabriella Miller Kids First Pediatric Research Program to support rapid generation of high quality sequence and variant data (whole genome, RNA, and long-read), genome-wide methylation profiling, and chromatin accessibility data from a large number of human specimens representing two types of pediatric conditions - childhood cancers and structural birth defects. All data generated under this FOA will be re-processed and harmonized by the Gabriella Miller Kids First Pediatric Data Resource Center (Kids First DRC), which is also charged with maintaining a public-facing, cloud-based resource that enables researchers to search, access, aggregate, analyze, and share annotated genomic sequences, genomic variants, epigenomic, transcriptomic, and phenotypic datasets. Together these resources promote comprehensive and cross-cutting research and collaboration within the pediatric research community.

Key Dates

Posted Date
August 17, 2021
Open Date (Earliest Submission Date)
September 29, 2021
Letter of Intent Due Date(s)

Not Applicable

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
Not Applicable October 29, 2021 Not Applicable March 2022 May 2022 July 2022

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.

Expiration Date
October 30, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Introduction

In response to the Gabriella Miller Kids First Act (https://www.govtrack.us/congress/bills/113/hr2019/text), NIH, through the Common Fund, has established the Gabriella Miller Kids First Pediatric Research Program (Kids First). Kids First seeks to foster collaborative research to uncover the genetic etiology of childhood cancer and structural birth defects. In pursuit of this goal, the program is developing the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource), which includes a public-facing portal and other resources that enable researchers to search, access, aggregate, analyze, and share annotated genomic sequence, variant, and phenotypic datasets. This resource is of high value for the pediatric research community and facilitates analyses across diverse conditions to uncover shared developmental pathways. The overall goal is to help researchers understand the underlying mechanisms of these conditions, leading to more refined diagnostic capabilities and ultimately more targeted therapies or interventions.

The Kids First program uses the X01 mechanism (see: PAR-21-040) to solicit proposals for the generation of genomic and epigenomic data from samples collected from childhood cancer and structural birth defects cohorts. Future calls for X01 projects will be published to continue identifying childhood cancer and structural birth defects projects each year of the sequencing center award(s), pending availability of funds.

This FOA invites applications for existing Kids First sequencing center (s) to produce genomic (e.g., whole-genome sequences and variants, long-read sequences and variants), transcriptomic (e.g., RNA sequence and expression data), epigenomic (e.g., genome-wide methylation profiling, chromatin accessibility assays), and associated derived data from cohorts identified through X01 proposals to contribute to the Kids First Data Resource for sharing with the research community.

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Goals

The goals of this FOA are as follows:

  • Generation of high quality genomic, transcriptomic, and epigenomic data from childhood cancer and structural birth defects cohorts that the Kids First Program will select through the X01 mechanism described above.
  • Submission of individual-level genomic, transcriptomic, epigenomic sequences, derived data, and metadata to the Kids First Data Resource Center, which is serving as the NIH-designated repository for this program, and any other databases that may be designated by the Kids First Program, as well as providing the same data to the project/sample Program Directors/Principal Investigators (X01 PDs/PIs), as needed.
  • Coordination with project/sample PDs/PIs who will submit samples as well as coordination with the Kids First Data Resource Center to fulfill program goals.

The FOA expects high quality genomic, transcriptomic, epigenomic sequences and derived data to be generated from the largest number of cases and samples possible with available funds. It is anticipated that throughput and costs will improve over the course of the award while data quality is maintained or enhanced, so the number of cases and diversity of conditions that can be sequenced and analyzed per dollar spent are expected to increase.

Coordination and Governance

The center(s) under this FOA will be funded using a cooperative agreement. The center(s) will be required to closely interact with X01 project/sample PDs/PIs on sample transfer and QC, project design, data generation, and data transfer. If two centers are funded, coordination between the centers will be necessary to assure comparable data quality, standards, and formats, and to avoid unnecessary duplication of efforts. In addition, the selected center(s) are expected to communicate and closely coordinate with the Kids First Data Resource Center (DRC). Close interactions with the NIH program staff will also be required to ensure appropriate and timely project assignments to the funded center(s) and satisfactory progress toward the FOA and program goals. The activities to be coordinated include, but are not limited to, establishing data standards and formats, establishing communications for sample tracking and data generation, and coordinating data transfer for access by X01 project/sample PDs/PIs and submission of individual-level genomic, transcriptomic, epigenomic sequence, derived data, and metadata to the DRC for public sharing.

In addition to the NIH Kids First Working Group, a Steering Committee will contribute to governing the Kids First Program. The Steering Committee will be composed of the PIs of the Sequencing Center(s), Kids First Data Resource, representatives of X01 project/sample PDs/PIs, NIH program staff, and an NIH-appointed Chair. An independent group of Program Consultants will be engaged by the NIH to evaluate the progress of the program and to provide advice to the program about scientific direction.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
Renewal

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

The NIH Common Fund intends to fund one or two awards, corresponding to a total of $7M for fiscal year 2022 and $3-4M in FY2023 - FY2024, pending annual appropriations and sample availability.

Award Budget

Application budgets for each year should not exceed $7.2M in total costs.

Award Project Period

The total maximum award period for this FOA is 3 years (FY2022 - FY2024).

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

Eligibility is limited to the awardees of RFA-RM-18-030.

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not 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.
  • 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

This is a limited competition open only to the existing Kids First Sequencing Centers.

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

 

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Up to 5% of the total budget can be devoted to custom analysis and validation of a selected set of variants in collaboration with X01 project/sample PDs/PIs after the generation of VCF files.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Applicants should address the following aspects. Relevant previous experience should be described succinctly.

A) Sample Management and Data Production

  • Sample coordination and processing.
    Centers are expected to provide shipping instructions to X01 investigative teams, including reminders to use subject and sample IDs that are two-steps removed from personal information per dbGaP requirements. Coordination should include receipt, QC, verification, tracking, and storage of de-identified nucleic acids. Protocols for isolating DNA from tumor (frozen or paraffin embedded) and blood specimens, and DNA quality and yield, should be described. While project/sample PDs/PIs are expected to extract nucleic acids prior to shipping to the sequencing center, sequencing center staff may be asked to suggest protocols and provide guidance for technically challenging tissue types (e.g., paraffin embedded tumor) and in some instances to carry out these extractions.
  • Genomic, transcriptomic, and epigenomic sequences and derived data generation.
    Applicants should describe the facilities, data generation platform(s), and analytical pipelines that will be used for the proposed activities. Activities should include genomic (e.g. whole-genome, long-read sequencing), transcriptomic (e.g. RNA sequencing) and epigenomic (e.g. genome-wide methylation profiling, chromatin accessibility assays) data generation. Protocols for 1) generation of libraries or raw data, 2) sequence or equivalent data generation, 3) storage and transfer of BAM, CRAM, or equivalent files, 4) generation, storage, and transfer of Variant Call Format (VCF) or equivalent files, and 5) quality metrics, should be described.

    This FOA anticipates that the following types of cohorts will be sequenced and analyzed: 1) structural birth defects in families such as “trios”(proband, mother, father) or multiplex/multigenerational pedigrees; 2) childhood cancers in families with or without tumor, such as “quads” (normal from proband, tumor from proband, mother, father). The Kids First program will also accept X01 applications that include sequencing of affected somatic tissue from structural birth defects cohorts as well as “tumor trios” for childhood cancer cohorts (normal from proband and tumor samples from multiple time points: pre-treatment, post-treatment, relapse, and/or metastasis), when justified. In addition, the X01 sample/project PDs/PIs may propose other types of cohorts to be sequenced and analyzed by the funded center(s).Genome sequencing center applicants should propose plans for 1) appropriate whole genome sequence and transcriptome coverages for these types of cohorts and samples, 2) methods for identifying germline or somatic genomic variants from the sequence data, and 3) methods for epigenomic profiling of tumors and/or affected tissue. Types of genomic variants to be identified should include SNVs, indels, and structural variants. Applicants should propose timelines from having samples in house through delivering the sequence data and VCF files to X01 project/sample PDs/PIs and the Kids First DRC. The flexibility of the data generation, data processing, and variant calling pipeline to accommodate possible fluctuation of sample availabilities should be described as well (e.g., processing and submitting data in batches).

    After the delivery of genomic, transcriptomic, epigenomic sequences, derived data, and metadata, the next step may be custom analysis and/or validation of variants for a subset of cases by the center(s) or between the centers and the X01 project/sample PIs, if both parties are interested in pursuing such collaborations. With NIH approval, the funded center(s) may spend a small portion of the total budget(s) for this type of scientific collaboration (see the instruction for R&R Budget). Applicants interested in pursuing such collaboration should describe the methods that will be applied and products that will be delivered.

    Finally, to demonstrate the readiness for performing all of the above activities, applicants should describe relevant examples of previous success.

B) Computational and bioinformatics capacity.

Computational and bioinformatics capacity to support sample processing, data (genomic, transcriptomic, and epigenomic) generation, processing, and QC, variant calling and validation, data storage, and data transfer to X01 project/samples PIs and the Kids First DRC or other NIH-designated repositories, should be included. Sequencing centers should describe their plans and timelines for hosting data files generated for the program; in general, it is expected the centers will store data for at least one year after data generation completes.

C) Costs

Applicants should provide the following itemized costs.

  • Per sample cost for each data type
    Applicants should estimate the per-sample cost for each type of data production and analysis (e.g. whole-genome, long-read sequencing, RNA sequencing, genome-wide methylation profiling, chromatin accessibility assays) per sample. These estimates should factor in, but are not limited to, the following items:

Sample intake and processing
Library preparation
Data production (e.g. standard short-read whole genome sequencing, long-read sequencing, RNA sequencing, ATAC sequencing, Methylation profiling)
Generation of VCF or other derived files
QC
Experimental failures
Equipment
Computational and bioinformatics costs
Labor
Indirect costs

Describe whether the cost estimates vary for different sample sources (e.g., blood, saliva, frozen tumor, paraffin embedded tumor). Separately, provide estimates for DNA/RNA isolations.

  • Total number of samples to sequence and analyze.
    The applicant should estimate the minimum number of samples for which the proposed center can generate a complete set of genomic, transcriptomic, epigenomic and derived data, with annual breakdowns that factor in a cost reduction plan. For the sake of the application, assume equal number of samples in each of the two cohort types. For reference, the Kids First Program so far has identified approximately 6,000-10,000 samples per year. It is anticipated that fewer samples will be solicited each year.
  • Cost reduction.
    Plans for decreasing all of the above costs over the years of this award while improving efficiency and quality should be proposed.
  • Complementary sequencing approaches.
    Plans for using complementary sequencing approaches not discussed above (e.g., whole exome sequencing) can be proposed with a rationale that considers unit costs, scale up costs, data quality, and added scientific value for specific sample and variant types.

D) Management Plan

A management plan for the proposed center should be proposed. The plan should describe the organization, reporting, and communication structure within the proposed center including the roles of key center members and decision-making processes. The plan must assure adequate personnel for 1) the generation and delivery of genomic, transcriptomic, epigenomic and derived data to X01 investigators and the DRC; and 2) coordination with NIH Kids First Program staff. Overall, the plan should discuss how the proposed organization and management structure will likely lead to success in attaining the goals of the center and the Kids First program.

E) Coordination and Communication with the Kids First Data Resource Center

One major component of the Kids First Data Resource Center (DRC) is to serve as a Data Coordinating Center to track, ingest, process, harmonize, store, and distribute data generated by Kids First sequencing centers. Therefore, sequencing centers are expected to coordinate and communicate with the DRC on activities that include, but are not limited to:

  • Sample-Level Data Tracking.
    The DRC is tasked with tracking and reporting sample-level status reports for the Kids First program. Sequencing centers are expected to communicate sample-level status updates to the DRC including: date of shipment receipt, QC results (including details about samples that fail QC), updates on when sequencing starts and completes, and notifications when data is available.
  • Data Transfer and Delivery.
    Kids First sequencing centers are responsible for submitting genomic, transcriptomic, epigenomic, and derived data to the Kids First DRC, which is serving as the controlled-access public database for this program and is responsible for distributing Kids First data to the research community. Additionally, sequencing centers are responsible for delivering data to the project/sample PDs/PIs, which can be facilitated by and coordinated with the Kids First DRC.
  • File Formats and Analytical Pipelines.
    For whole genome data, sequencing centers are expected to provide to the DRC, at minimum, 1) individual-level sequence read files aligned to the most recent reference genome (e.g., BAM or CRAM aligned to GRCh38) and/or raw unaligned data files with associated metadata (e.g., FASTQ), and 2) individual-level variant data (e.g., VCF). Sequencing centers should describe what file formats they intend to provide for whole genome sequence as well as RNA sequence, genome-wide methylation, and chromatin accessibility profiles. Decisions regarding formats and analysis pipelines of sequence and variant data will be finalized in discussions with the NIH.

Although this list is not exhaustive, such activities require close coordination between sequencing centers and the DRC. Therefore, sequencing center applications should include a plan for how they will communicate and coordinate with the DRC to fulfill the expectations described above.

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

The following modifications also apply:

Where appropriate, applicants should consider using community and global standards such as those developed by the Global Alliance for Genomics and Health (GA4GH).

It is expected that tools, workflows, and/or pipelines created or used with support from this FOA will be well-documented and shared with the wider scientific community, in a timely manner that would enable other researchers to replicate and build on for future research efforts. In the Data and Resource Sharing Plan, applicants should describe the anticipated timeline, formats, and methods of sharing pipelines or software created or used under this FOA (e.g. through Docker, public GitHub links).

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential 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 NHGRI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

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

Investigator(s)

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

Specific to this FOA: Do the PDs/PIs have successful experience in performing large-scale whole genome and transcriptome sequencing and variant identification for human structural birth defects and cancers using state-of-the-art technologies and methods? Do the PDs/PIs have successful experience in managing multiple collaborative projects simultaneously?

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?

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 FOA: Will the proposed approaches lead to large volume and -high-quality sequence and variant data from Kids First samples in a highly efficient and cost-effective way? Will the management plan enable the proposed center and the program as a whole to meet the goals of the application? Does the application include a plan for coordinating and communicating with the X01 investigators and the DRC on activities including sample tracking, data transfer, and data delivery? Is the center willing to share raw and derived data files (e.g., FASTQ, BAM, or CRAM, and VCF or gVCF) with the DRC in order to enable data harmonization and sharing?

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

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

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). Reviewers will comment on whether there is a plan for sharing tools, workflows, and/or pipelines created or used with support from this FOA.

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

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

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Advisory Council. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
  • Willingness and capacity to coordinate and collaborate with Kids First X01 investigators and the Data Resource Center.
  • Compliance with resource sharing expectations.

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.

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

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

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

2. Administrative and National Policy Requirements

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR 200 and other HHS, PHS, and NIH grant administration policies.

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

The PD(s)/PI(s) will have the primary responsibility to:

  • Accept close coordination, cooperation, and participation of the NIH staff in the aspects of scientific and technical management of the project as described below.
  • As requested by NIH staff, provide the funded center’s goals and associated throughput, quality, and cost information. These are usually requested at the outset of the award and annually thereafter, but can also be at other times.
  • Determine the approaches for data generation and variant identification, and carrying out those efforts.
  • Ensure that all center goals are met.
  • Determine ways to establish and disseminate workflows and best practices for data generation and variant identification from Kids First samples.
  • Ensure effective interaction with X01 project/sample PIs, the Kids First Data Resource Center, the NIH staff, and the other sequencing center if two centers are funded.
  • Adhere to the NIH policies regarding intellectual property, data sharing and other applicable resource sharing policies.
  • Ensure that the data are deposited into appropriate public databases, and that developed resources, including analytical pipelines, are made publicly available in a timely manner that would enable other researchers to replicate and build on for future research efforts.
  • Accept and implement any procedures and guidelines developed and approved for the Kids First Program.
  • Accept and participate in the cooperative nature of the Kids First Program, including
  • Attending the Steering Committee meetings;
  • Coordinating and collaborating within the Kids First Program as described above;
  • Where opportunities are identified, participating in collaborations with other NIH research networks.

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

NIH staff will have the role of Project Scientists through technical assistance, advice, and coordination. However, the role of the Project Scientists will be to facilitate but not to direct the activities.

Project Scientists' responsibilities are defined as follows:

  • Make decisions about assignment of projects to a sequencing center and the final project design.
  • Participate (with other Steering Committee members) in the group process of setting project priorities and making decisions on joint activities and standard practice of the Kids First Program. The Project Scientists will assist and facilitate the group process but not direct it.
  • Negotiate goals and timelines with the recipientss, as necessary.
  • Serve as liaisons between the recipientss, Steering Committee, the NIH Kids First Working Group, and the larger scientific community in helping the Kids First Program to achieve its goals. Serving on subcommittees of the Kids First Working Group, as appropriate.
  • Coordinate the efforts of the Kids First Program with others engaged in similar and related activities.
  • Attend all Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
  • Periodically report progress to the Director of NIH.
  • Liaise between the recipients, Steering Committee, and the NIH Kids First Working group and serving on subcommittees of the Kids First Working Group, as appropriate.
  • Assist in promoting the availability of the data generated by the Kids First Program to the scientific community at large.
  • Where warranted, co-author publications about the goals of this FOA, and of results of studies funded under this FOA.

Additionally, an agency program official or institute program will have a major stewardship role in the management of the award(s) and will be named in the award notice(s). This stewardship will include evaluation and monitoring progress with respect to the achievement of specific aims, completion of project milestones, timely transfer of data, conformance to regulatory and policy requirements, fiscal accountability, and adherence to any special terms and conditions of the award. In addition, the Program Official will be responsible for approval of budget adjustments and changes in technical or scientific plans that potentially constitute a change in scope of the project, approval of changes in key personnel or their effort on the project and approval of any carryover or supplemental funding requests. The Program Official will continually assess risk regarding potential issues related to accomplishing the scientific aims of the research and protection of human subjects, taking appropriate actions if serious problems are identified.

Areas of Joint Responsibility include:

In addition to the NIH Kids First Working Group, a Steering Committee will contribute to governing the Kids First Program. The Steering Committee will be composed of the PDs/PIs of the Kids First Sequencing Center(s), the PDs/PIs of Kids First Data Resource Center, representatives of X01 sample/project PDs/PIs (one from structural birth defects community and one from the childhood cancer community), NIH program staff, , and an NIH-appointed Chair. The Steering Committee Chair will be appointed by the Kids First Working Group and will not be an NIH staff member or a Kids First funded investigator. Other government or recipient staff may attend the Steering Committee meetings if their expertise is required for specific discussions.

The Steering Committee may be asked to:

  • Establish the milestones under this FOA, in consultation with the NIH Kids First Working Group.
  • Help develop uniform procedures and policies necessary to meet Program goals, in consultation with the NIH Kids First Working Group.
  • Provide input on issues that arise and brainstorm solutions.
  • Provide information to the Program Consultants, who will be appointed by the NIH. The Program Consultants will evaluate the progress of the Kids First Program and the Program’s recipientss and provide advice to the NIH about scientific direction.

Dispute Resolution:

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

3. Reporting

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

James Coulombe, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-1390
Email: coulombej@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Bonnie Jackson
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-5482
Email: jacksobo@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, 45 CFR Part 75, and 2 CFR 200.


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