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)

Funding Opportunity Title

ENCODE Data Analysis Center (U24)

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices

  • January 22, 2016 - Notice of Applicant Information Webinar for NHGRI ENCODE RFAs: RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, RFA-HG-16-005, and RFA-HG-16-006. See Notice NOT-HG-16-007.
  • NOT-HG-15-037

  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)
Funding Opportunity Announcement (FOA) Number

RFA-HG-16-006

Companion Funding Opportunity

RFA-HG-16-002, UM1 Research Project with Complex Structure Cooperative Agreement
RFA-HG-16-003, UM1 Research Project with Complex Structure Cooperative Agreement
RFA-HG-16-004, U01 Research Project – Cooperative Agreements
RFA-HG-16-005, U24 Resource-Related Research Projects – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.172 

Funding Opportunity Purpose

The purpose of this FOA is to solicit applications to develop and implement a Data Analysis Center (DAC) for the ENCyclopedia Of DNA Elements (ENCODE) project.  The DAC will provide leadership and computational expertise to analyze data from the ENCODE project, specify and update data processing pipelines and quality metrics for major data types, design and perform integrative analysis of ENCODE data to update and refine the Encyclopedia (a major ENCODE product for the research community) and develop a scientific strategy to characterize the ENCODE sample portfolio both for the short-term goal of prioritization of new data collection, and the longer-term goal to assess the comprehensiveness of the sample space that has been examined.  The DAC will work closely with another ENCODE component, the Data Coordinating Center (DCC), described in the companion FOA, RFA-HG-16-005, to form an integrated ENCODE Data Coordination and Analysis Center (EDCAC). The funded DCC and DAC projects will be expected to coordinate their activities, and to participate in and coordinate activities of the ENCODE Consortium.

Key Dates
Posted Date

January 14, 2016

Open Date (Earliest Submission Date)

February 21, 2016

Letter of Intent Due Date(s)

February 21, 2016

Application Due Date(s)

March 21, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

June 2016

Advisory Council Review

October 2016

Earliest Start Date

December 2016

Expiration Date

March 22, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

The purpose of this FOA is to solicit applications to develop and implement a Data Analysis Center (DAC) for the ENCyclopedia Of DNA Elements (ENCODE) project.  The DAC will provide leadership and computational expertise to analyze data from the ENCODE project, specify and update data processing pipelines and quality metrics for major data types, design and perform integrative analysis of ENCODE data to update and refine the Encyclopedia (a major ENCODE product to the research community) and develop a scientific strategy to characterize the ENCODE sample portfolio both for the short-term goal of prioritization of new data collection, and the longer-term goal to assess the comprehensiveness of the sample space that has been examined.  The DAC will work closely with another ENCODE component, the Data Coordinating Center (DCC), described in a companion FOA to form an integrated ENCODE Data Coordination and Analysis Center (EDCAC). The funded DCC and DAC projects will be expected to coordinate their activities and to participate in and coordinate activities of the ENCODE Consortium. 

Background

A critical step in moving from genome sequence to understanding the impact of genetic variation on biology, health and disease is the identification of the parts of the genome that contribute to function. To facilitate this understanding, the National Human Genome Research Institute (NHGRI) has been supporting the Encyclopedia of DNA Elements (ENCODE) Project (www.genome.gov/ENCODE).  The long-term goals of ENCODE are to identify all of the sequence-based functional elements in the human genome and to share catalogs of these elements freely with the research community in readily accessible and interpretable formats.  ENCODE aims to annotate both protein-coding and non-coding regions of the genome. To date, fewer resources have been devoted to the study of non-coding variation, but evidence for its important role in establishing healthy and disease phenotypes continues to grow. Genome-wide association studies (GWAS) have revealed that most disease-associated variants map to non-coding regions, and most of the heritability of common diseases has been imputed to stem from non-coding regions. Non-coding variation accounts for most of the heritability in the Mendelian disorder Fragile X Syndrome, and is a major source of heritability in polygenic disorders such as Amyotrophic Lateral Sclerosis. As whole genome sequencing is increasingly being undertaken to understand the genetic basis of disease, the importance of being able to interpret these data in their entirety (including non-coding regions) will increase. NHGRI and ENCODE are thus especially interested in creating resources to help researchers interpret non-coding genome variation. 

The main strategy employed by ENCODE has been the identification of candidate functional elements using genome-wide biochemical assays associated with specific classes of DNA elements. This approach has been augmented by comparison of sequences and candidate elements across species.  “Functional elements” are genes (protein-coding and non-coding) and regulatory regions. Decades of gene regulation studies have identified mechanistic events (such as changes in chromatin structure and protein occupancy) that are being used to make predictions of regulatory elements; given that the accuracy of any untested prediction is unknown, the term “candidate functional elements” is used here.  As many functional elements are manifest only in specific cellular contexts, multiple cell types have been interrogated to maximize discovery of candidate elements.  A portion of ENCODE’s effort has been devoted to analysis of the mouse genome, as annotation of the mouse genome has facilitated understanding of the human genome. 

Candidate functional elements that have been identified by ENCODE include genes, RNA transcripts, regulatory elements encoded in DNA (including enhancers, promoters, and insulators) and regulatory elements acting at the RNA level (including those that regulate splicing, translation, and RNA stability). ENCODE has used genomic methods (e.g., RNA-seq, ChIP-seq, DNase-seq) based on biochemical assays that have been developed and widely used by the research community to study gene regulation. These assays, which map features that have been mechanistically linked to gene regulation, have been used by epigenomics projects (such as ENCODE, the Roadmap Epigenomics Mapping Centers [REMC], and the International Human Epigenome Consortium [IHEC]), as well as many individual investigators in the research community to identify functional regions of the genome.

Any researcher may freely download, analyze and publish results based on any ENCODE data (without embargo or restrictions) as soon as the data are released. The catalogs of candidate elements are intended to complement ongoing efforts to understand the functions resident in the genome and to serve as the basis for hypothesis generation for more focused studies.  As of October 2015, ENCODE has released approximately 3500 experiments, each containing at least two replicates, examining approximately 300 human cell types (cell lines, primary cells, cells differentiated in culture, and explants), and approximately 1000  experiments in more than 150 mouse cell types. To date, ENCODE human and mouse data have appeared in approximately 1200 papers published by researchers outside of ENCODE, including investigations of the role of the genome in human disease (https://www.encodeproject.org/search/?type=publication&published_by=community).

ENCODE is also integrating these data to produce an “Encyclopedia,” a compendium of candidate functional elements designed to enable exploration of the role of functional elements in disease mechanisms and basic biological processes.  A developmental version of the Encyclopedia is available at https://www.encodeproject.org/data/annotations/

NHGRI convened a planning workshop “From Genome Function to Biomedical Insight: ENCODE and Beyond” on March 10-11, 2015, to consider what projects in functional genomics should be supported that build on the work of ENCODE. Details about this workshop, including the workshop report can be found at: http://www.genome.gov/27560819. The overall conclusion from the workshop was that much work still remains to complete the Encyclopedia and to maximize its utility:  While many elements are functionally active in restricted cell contexts, only a small fraction of these (cell types, fates, states) have been studied to date.  Further, only a very small fraction of the candidate functional elements have been experimentally characterized with respect to specific biological function(s) and new technologies have emerged over the past few years that have made the cost-effective and high-throughput study of these biological functions feasible.  Functional studies on samples related to disease serve as an untapped opportunity to simultaneously expand the Encyclopedia, provide insights about disease and help uncover general strategies for applying these assays to disease.  Finally, to meet the long-term goals of functional genomics, continued technology development is needed.   

Based on the workshop recommendations, NHGRI proposes to extend the ENCODE effort through the support of five Funding Opportunity Announcements (FOAs) to address the following specific goals: expand the catalog of functional elements; move beyond cataloging towards a general understanding of the functional role of genomic elements, which occurs in specific biological contexts; develop strategies to apply these studies to disease; increase the number of scientists from the research community contributing to the creation of the Encyclopedia of functional elements; develop analytical tools to enhance the utility of the data; and make the data, tools, analyses and assembled Encyclopedia freely available to the research community. 

These related initiatives are: 

  • RFA-HG-16-002; “Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Mouse (UM1)” seeks to expand the catalog of candidate functional elements by soliciting applications to conduct high-throughput data-generation experiments to map biochemical activities associated with specific functional elements in the human and mouse genomes.  These are referred to as “Mapping Centers”.
  • RFA-HG-16-003; “Characterizing the Functional Elements in the Encyclopedia of DNA Elements (ENCODE) Catalog (UM1)” solicits applications to develop and apply generalizable approaches to characterize the role of candidate functional elements in specific biological contexts.  These are referred to as “Characterization Centers”. 
  • RFA-HG-16-004, “Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data (U01)” solicits applications to support computational analysis of ENCODE data.
  • RFA-HG-16-005; “ENCODE Data Coordination Center (U24)” solicits applications to establish an ENCODE Data Coordination Center (DCC) to support the data management and consortium activities for the next phase of ENCODE. 
  • RFA-HG-16-006; “ENCODE Data Analysis Center (U24)” solicits applications to establish an ENCODE Data Analysis Center (DAC) to support the centralized data analysis needs of the next phase of ENCODE.

NHGRI plans to support technology development efforts through other, broader initiatives (see:  PAR-16-014, PAR-16-015, PAR-16-016, PAR-16-017).

ENCODE will be organized as a Research Consortium that brings participants together in a highly collaborative and synergistic effort. Data produced in the Mapping Centers (funded through RFA-HG-16-002) as well as by the Characterization Centers (funded through RFA-HG-16-003) will serve as the raw material for generating annotations of functional DNA sequence elements. These data will be submitted to the ENCODE Data Coordination Center (DCC, funded through RFA-HG-16-005).  The DCC will uniformly process the mapping data as well as develop, house, and maintain databases to track, store, and provide access to all ENCODE data and related resources.  The DCC will also import from the research community related mapping data that meet ENCODE quality standards.  The ENCODE Data Analysis Center (DAC, funded through RFA-HG-16-006) will coordinate high-level analytical activities of the consortium, including development of the Encyclopedia, and provide computational support for these analyses. Computational Analysis groups (funded through RFA-HG-16-004) will develop novel methods and tools for processing, analyzing, and enhancing the utility of ENCODE data, and contribute broadly to consortium analytical efforts.

Research Scope

The ENCODE Data Coordination and Analysis Center (EDCAC) will be an integrated, stable resource that will gather data and metadata from the ENCODE Project, integrate those data with genome sequences, serve as a resource from which the community can readily access ENCODE data, analyses, tools, and methods, and create and make available a high quality Encyclopedia of candidate functional elements. It will be comprised of two components:  a Data Coordination Center (DCC) funded through RFA-HG-16-005 and a Data Analysis Center (DAC) funded through this FOA. The EDCAC should be prepared to work with data and metadata from the range of different experimental and computational projects that are expected to be funded through the companion FOAs (RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, RFA-HG-16-005), as well as functional genomics data derived by groups operating outside the ENCODE Consortium.  As the identity of the actual funded projects will not be known at the time that the applications in response to this FOA are due, and given the disparate functional genomics data types created by the broader community, it will be necessary for applicants to design a general plan that addresses the data currently being produced by the ENCODE projects, as well as other types of data related to functional sequence elements. A description of data and resources being produced in the current phase of the ENCODE project may be found at https://www.encodeproject.org.

This FOA solicits applications for a Data Analysis Center (DAC) to perform and lead integrative analyses necessary to produce the Encyclopedia (see below), while the Data Coordination Center (DCC), described in companion FOA, RFA-HG-16-005, will provide the data management functions and coordinate consortium activities.  Once awards are made, the DCC and DAC awardees will be expected to work together as a highly coordinated team to provide a single, integrated EDCAC.

Coordination will be required between the DAC and the DCC to avoid duplication of effort and to ensure compatibility. For example, currently the DCC and DAC work together on uniform data processing, with the DAC leading the effort to specify the pipelines, and the DCC leading the effort to implement them. They also work together on the portal, with the DCC leading the efforts on user interface and databases, and the DAC leading the effort to decide what analyses to perform. As the data storage, analysis, and dissemination needs of the Consortium change with time, either or both components of the EDCAC may be asked to modify their workflows as agreed upon by the ENCODE Consortium. Both elements of the EDCAC should be flexible in their implementation of data management and analysis workflows.

The following are essential functions of the Data Analysis Center:

1) Analyzing and integrating data and metadata from a broad range of experimental and computational functional genomics projects. 

These data will include those generated by projects funded through the companion FOAs (RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, RFA-HG-16-005), as well as functional genomics data derived by groups operating outside the ENCODE Consortium.

2) Creating high quality Encyclopedias of DNA elements in the human and mouse genomes.

The Encyclopedias will be comprehensive catalogs of functional elements and will serve as resources to enable the broader scientific community to seek new advances in both basic and clinical knowledge, and may build on those currently under development (https://www.encodeproject.org/data/annotations/). The goal will be to generate catalogs of human and mouse functional elements that define features of the genome such as gene models, regions of open chromatin, regions enriched in select histone modifications, RNA transcripts, binding sites for transcription factors and binding sites for RNA-binding proteins on transcripts.  These elements will be elucidated by high-throughput methods such as RNA-seq, ChIP-seq and DNase-seq.  A key feature of the Encyclopedias will be integrative predictions of functional element subtypes such as enhancers, promoters, silencers, RNA-editing sites, and others.

3) Serving as an informatics resource by supporting the activities of the ENCODE Analysis Working Group (AWG).

The DAC will be a member of the AWG, and will work with the informatics components of the individual ENCODE data production centers and AWG to coordinate and facilitate integrative analyses of the ENCODE and related data. The DAC will provide resources and coordination activities that will enable the ENCODE Consortium to provide useful information about functional sequence elements in the human and mouse genomes to the larger biomedical research community. The DAC will support activities within the ENCODE AWG that include but are not limited to developing uniform data processing pipelines to standardize the ENCODE data analyses, assessing the quality of the ENCODE data, assisting the AWG to integrate data to find either new elements and to define the biological roles of identified elements, and informing the ENCODE Consortium and the NHGRI on the progress towards completing the comprehensive catalog of functional elements.  During the course of the project, the DAC may develop new methods to assess the quality of ENCODE data that may be incorporated into the ENCODE data standards.  Additional analysis activities to use ENCODE data to derive insights into how these functional elements interact during a biological process or into disease mechanisms are not appropriate under this FOA. Applications to support those activities are being solicited by the companion FOA RFA-HG-16-004.

4) Assessing quality and utility of the ENCODE data and providing feedback to NHGRI and the Consortium. 

An aspect of the DAC efforts in the next phase of ENCODE will be a critical, cost-benefit analysis of the relative value of the different data types being generated to determine if it is possible to identify a minimum core set of data types that can serve as a surrogate for a comprehensive catalog of functional elements.  Such a core set could be useful in directing data generation for more focused analyses, especially disease-specific analyses. Activities will include analysis of Consortium data to characterize the ENCODE sample portfolio both for the short-term goal of prioritization of new data collection and the longer-term goal to assess the comprehensiveness of the sample space that has been examined. This could lead to an operational bounding of the epigenomic/transcriptomic space that could be usefully profiled by ENCODE.

The DAC will work with data generated from both human and mouse.  The emphasis of the next phase for the ENCODE Project will be on the human genome and, to a lesser extent, the mouse genome.

Participation as Part of a Research Consortium:  Groups funded under this initiative will be expected to collaborate effectively with each other to maximize the chances of overall success of the program and to participate in the ENCODE Research Consortium. The Awardees funded through the concurrent FOAs, RFA-HG-16-002; “Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Mouse (UM1)”, to support mapping of functional elements,  RFA-HG-16-003, “Characterizing the Functional Elements in the Encyclopedia of DNA Elements (ENCODE) Catalog”, to support characterization of candidate functional elements, RFA-HG-16-004 “Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data”, to support additional analysis activities, and RFA HG-16-005 “ENCODE Data Coordination Center", to support ENCODE’s data management and Consortium coordination and outreach activities, will also participate in the ENCODE Research Consortium.

This FOA is open to all investigators, specifically including those who are not currently participating in the ENCODE Project. Applicants are free to apply to the companion FOAs. However, to encourage participation from a broad representation of the research community, when making funding decisions, NHGRI intends to consider whether an applicant will be funded as a PD/PI through other ENCODE FOAs and may choose to limit awards from multiple FOAs. As in the ENCODE Project to date, the ENCODE Research Consortium will continue to be open, beyond investigators funded through the above FOAs, to all academic, government and private sector scientists who are interested in participating in an open process to facilitate the generation of comprehensive catalogs of the ENCODE-targeted genomes.

All applicants are strongly encouraged to contact NHGRI Staff to discuss the alignment of their proposed work with the goals of this FOA, and with the ENCODE Project. A Technical Assistance teleconference will be held for potential applicants to this FOA and the companion FOAs.  NHGRI staff will be available to answer questions related to this FOA.  Time, date, and dial in information for the call will be announced in an NIH Guide Notice and will be posted on the ENCODE website:  www.genome.gov/ENCODE. During the Information Session, NHGRI staff will present an overview of these FOAs and answer questions from prospective applicants.  The Information Session is open to all prospective applicants, but participation is not a prerequisite to applying.

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

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NHGRI intends to commit $2 million to $3 million in FY 2017 to fund one award.

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is four years.  

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • U.S. Territory or Possession
  • Other
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • 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) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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.

Applicants responding to this FOA may apply for the DCC through the companion FOA RFA-HG-16-005, but separate applications will be required for each.  An applicant may not submit a single application that combines the two components.  This FOA is open to all qualified individuals and institutions and does not require prior participation in earlier phases of the ENCODE project.

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

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

2. Content and Form of Application Submission

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

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

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:

Mike Pazin, Ph.D.
Telephone: 301-496-7531
Fax: 301-480-2770
Email: pazinm@mail.nih.gov

Please transmit Letter of Intent by email to pazinm@mail.nih.gov.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

  • For this specific FOA, the Research Strategy section is limited to 30 pages.
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.

Effective management will require a significant commitment by the Program Director(s)/Principal Investigator(s). For an application proposing a single PD/PI, that PD/PI is expected to devote at least 3 calendar months annually to the project. If multi-PDs/PIs are proposed, then one PD/PI is expected to commit at least 3 calendar months annually and the other(s) should devote sufficient time to serve his/her proposed role.

Budgets should include support for a dedicated Project Manager who will devote a minimum of 4 calendar months to oversee the day-to-day activities of the project, coordinate across project sites, if applicable, and be responsible for promptly providing requested reporting information to NHGRI Program Staff.  A PD/PI may serve as the Project Manager.

Budgets should include costs for bi-weekly Analysis Working Group calls for 50 participants and 4 bi-weekly working group calls for 20 participants each.

The ENCODE Project has regular conference calls and meetings. Awardees and additional key personnel from each center will be required to attend one Consortium meeting per year. 

Applicants should request funds for 2-6 group members to attend annual meetings and to attend Consortium-led tutorials, as appropriate.

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: The following items should be addressed in the application:

1) Plans to work with data and metadata from a broad range of experimental and computational functional genomics projects.

Applicants should describe plans to work with data and metadata generated by projects funded through the companion FOAs (RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, RFA-HG-16-005), as well as functional genomics data derived by groups operating outside the ENCODE Consortium, including specifying and updating data processing pipelines.  As the identity of the actual funded projects will not be known at the time that the applications in response to this FOA are due, and given the disparate functional genomics data types created by the broader community, it is expected that applicants will provide a general plan that addresses the data currently being produced by the ENCODE projects, as well as other types of data related to functional sequence elements.

2) Plans to create high quality Encyclopedias of DNA elements in the human and mouse genomes.

Applicants should describe:

  • Overall vision and specific plans to generate Encyclopedias that are comprehensive catalogs of functional elements capable of serving as resources to enable the broader scientific community to seek new advances in both basic and clinical knowledge, and which may build on those currently under development (https://www.encodeproject.org/data/annotations/).
  • Specific plans for presenting Encyclopedias in formats that are readily accessible and of high utility for a broad group of researchers.
  • Detailed descriptions of strategies for generating integrative predictions of functional elements, including subtypes of regulatory elements (e.g., enhancers, promoters, silencers, RNA-editing sites), transcripts, linkages between genes and regulatory elements, and others.

3) Plans to provide an informatics resource that will support the activities of the ENCODE Analysis Working Group (AWG).

Applicants should describe a broad plan for how the DAC will accomplish the goal of facilitating the work of the AWG, including a description of how the specific activities listed above will be accomplished.  This plan should be flexible enough to accommodate the analyses of new data types that might be available in the future and also should describe how the DAC will interact with the AWG, with the DCC, and with the rest of the ENCODE Consortium. 

Applicants should describe in their application:

  • Plans to work with informatics elements of individual ENCODE data production centers and the AWG to coordinate and facilitate integrative analyses of the ENCODE and related data.
  • Plans to support activities within the ENCODE AWG that should include but are not limited to: developing uniform data processing pipelines to standardize the ENCODE data analyses; assessing the quality of the ENCODE data; assisting the AWG to integrate data to find new elements and to define the biological roles of identified elements; and informing the ENCODE Consortium and the NHGRI on the progress towards completing the comprehensive catalog of functional elements.  
  • Plans to develop, if necessary, new methods to assess the quality of ENCODE data that may be incorporated into the ENCODE data standards. 
  • Plans to update existing and develop new data quality metrics and standards for all data types.
  • Strategy for coordinating with the DCC to provide support for any data analyses agreed upon by the AWG.
  • Strategy to facilitate interactions between ENCODE Consortium members and outside investigators to identify any additional datasets from outside of the ENCODE Consortium for use in integrative analyses.
  • Plans for specifying and updating data processing pipelines.
  • Plans for implementing regular conference calls to coordinate analyses.

In the past, ENCODE has found it useful for the AWG to recruit outside investigators to participate in ENCODE analyses to provide essential expertise or resources needed for specific AWG analyses. The applicant may request funds to support such additional investigators who are not identified in the application; if such funds are requested, the applicant should describe the process by which these additional investigators will be selected.

Other projects such as the International Human Epigenome Consortium (http://ihec-epigenomes.org) are generating data related to ENCODE and future projects may do so as well.  As the goal of the ENCODE Project is to provide a comprehensive catalog of functional elements, the applicant may describe a plan to identify these additional data and to use these data to improve the end product of the ENCODE Project.

4) Plans to provide feedback to NHGRI and the Consortium about the quality and utility of the ENCODE data. 

The applicants should describe general plans for a critical, cost-benefit analysis of the relative value of the different data types being generated to determine if it is possible to identify a minimum core set of data types that can serve as a surrogate for a comprehensive catalog of functional elements.  Such a core set could be useful in directing data generation for more focused analyses, especially disease-specific analyses, and could lead to an operational bounding of the epigenomic/transcriptomic space that could be usefully profiled by ENCODE.

Applicants should include in their descriptions:

  • Plans to analyze consortium data to characterize the ENCODE sample portfolio both for the short-term goal of prioritization of new data collection, and the longer-term goal to assess the comprehensiveness of the sample space that has been examined
  • Plans to perform cost-benefit analyses to define a minimum set of elements/marks needed to identify a unique molecular signature of an individual cell type that will benefit future data generation activities
  • Plans to provide reports to the ENCODE Consortium on the results from the integrative analyses
  • Plans to perform analysis of consortium data to expand the lexicon of functional elements beyond the basic categories (e.g., promoters and enhancers)

Additional information to consider in preparing the application:

It will be difficult to predict the exact volume and types of data that will be submitted over the lifetime of the next phase of the ENCODE Project.  Increasing efficiencies in generating data along with potential changes in technology platforms may dramatically alter the types and volume of data, while the addition of data from outside of the ENCODE Project also may add additional data volume and complexity.  It is expected that applicants will describe how they will prioritize their activities to ensure that the main goal of ENCODE, to generate Encyclopedias of functional elements, will be achieved. 

As the data storage, analysis, and dissemination needs of the Consortium change with time, the DAC may be asked to modify their workflows as agreed upon by the ENCODE Consortium.  Applicants should indicate their willingness to be flexible in their implementation of data management and analysis workflows. 

Software developed by the ENCODE DAC will be publicly released to the scientific community.  Applicants should describe plans: to make software modular and robust, and to include appropriate documentation and versioning, so that it can be used as a stand-alone package by the broader community; to leverage existing software projects as much as possible, where appropriate; and, to use standard formats for data input and output to facilitate its use and interoperability with other software, where appropriate.

The following additional items should also be addressed in the application:

  • Demonstration of Team Expertise Relevant to this FOA. The research team should provide evidence of team research productivity as a data analysis center in previous or ongoing genomics research networks.  The research team should also demonstrate the team capacity to scale activities as data volumes or complexity change within a research network.
  • Costs.  Applicants need to demonstrate an understanding of costs and how to track them, in particular the costs for computational infrastructure and personnel, including those responsible for working with the data producers on data submission.  The description of cost should propose a standardized cost structure, including useful units (e.g., per submitted experiment or per terabyte of data) on which to base costs for different aspects of the proposed projects.  Applicants should describe how these costs will change over the course of the project.  All cost analyses should include an explicit item for Direct Costs and then be presented in terms of Total Costs.
  • Technology Development.  Incremental technology improvements will play an important role in increasing the efficiency and decreasing the cost of the DAC.  NHGRI encourages applicants to include plans for such technology development activities in their applications, such as supporting new software tools to improve data management or analysis or making existing software more efficient.  The plans for technology improvement should be well described and the cost of the proposed technology development should be justified in terms of reducing operating costs for the DAC.  Any needed software development to implement these technology development activities should be described in detail.
  • Management Plan.   The application should describe how the proposed project will be managed, who will oversee the day-to-day activities (e.g., a project manager if not a PD/PI) and how the management structure will support achievement of the proposed goals and milestones. The management plan should address the appropriateness of the effort of key personnel, relative to their project roles. Useful elements of this description include the organization of the proposed project; its management structure, including the integration of the separate parts to form an efficient component of the EDCAC; ; section leaders and reporting relationships; and any advisory board, if relevant.  If included, the role of an advisory board should be described, including how often it will meet, what types of scientific expertise will be needed on the board, and what specific activities will be performed by the board members.  However, applicants should not contact potential advisors prior to the review of the application, nor should potential advisors be named in the application to avoid conflict of interest in the review process. Recruitment and training of personnel may also be discussed.  The plan should also describe how the various components of the proposed production effort will be integrated, and how collaborations or subcontracts, if proposed, will be managed.
  • Milestones and goals. Applications should define a clear set of goals for the proposed project and annual milestones with metrics that will document progress towards the achievement of the ultimate goals.  For the DAC, examples include, but are not limited to, milestones that track stages of Encyclopedia development and release, software development activities, turn-around time to either release submitted data to the ENCODE Portal or analyze particular datasets, or the number of defined analyses performed.  Applications should include plans for critically evaluating and revising these milestones on a regular basis.  The number and duration of milestones will depend on the project being proposed, so applicants should include these items for every year, as appropriate.  Milestones may be revised at the time of the award as described in the terms and conditions of a Cooperative Agreement in section VI.2.

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:

Data Sharing:  The NHGRI is committed to the principle of rapid data release to the scientific community from projects of broad community interest.  This principle was initially implemented during the Human Genome Project and has been widely recognized by the community as leading to one of the most effective ways of promoting the use of the genome sequence data to advance scientific knowledge. In keeping with this principle, the ENCODE Project has a history of rapid data dissemination to maximize access by the entire scientific community. ENCODE established and currently operates under a common Data Release Policy (see: https://www.encodeproject.org/about/data-use-policy/) of rapid pre-publication data release.  External data users may freely download, analyze and publish results based on any ENCODE data without restrictions as soon as they are released. Users of these data are asked to cite the ENCODE Consortium, as specified in the data release policy.  Agreement to abide by this policy is a current requirement for membership in the Consortium. NHGRI expects that the rapid data release principles of this policy will continue to be implemented during the next phase of the ENCODE Project.

Unrestricted access to human data:  As the current ENCODE Project has increased its study of primary cells and tissues, it has begun working on human  biological samples that have been explicitly consented for unrestricted data access in order to maximize the accessibility and broad utility of ENCODE data.  This means that data can be deposited and displayed in freely accessible databases, e.g., GEO (http://www.ncbi.nlm.nih.gov/geo/) without registration or request.  Moving forward, all samples to be studied under this initiative are expected to have been obtained using consents that (a) explicitly allow for unrestricted (open) data sharing and (b) allow for sharing samples with other ENCODE-funded groups.  (See http://www.genome.gov/ENCODE for sample language for open access consent forms and examples of open access consent forms previously used in ENCODE.)  Exceptions may be granted by NHGRI for studies employing new methods being applied across a relatively small set of common samples previously used within ENCODE (for which significant amounts of ENCODE data already exist). 

Applicants should propose a data release policy in their applications that addresses rapid data sharing with the community, consistent with achieving the goals of the project and with the current data release policy.  In addition, applicants should discuss the use of human biological samples obtained with consents allowing for unrestricted data access.  Specifically, applicants should describe previous experience with obtaining samples using consents allowing for unrestricted data sharing, if relevant, as well as the feasibility of obtaining such consent for biological samples proposed in the research plan, and indicate their agreement to obtain and use these appropriately-consented samples in the proposed studies.

After the initial review, NHGRI program staff will conduct an additional administrative review of the plan for sharing data and may negotiate modifications of the data sharing plan with the prospective awardee.  The final negotiated version of the data sharing plan will become a term and condition of the award of the cooperative agreement.

At the start of the next phase of ENCODE, the Consortium will review the current policy and the ENCODE Steering Committee will approve any updates, as appropriate; however, NHGRI expects that there will not be any significant change to this policy that will affect the timing in which data is released to the public.  Applicants should indicate their willingness to participate in the development of such a final plan and to accept it.

Software and Data Analysis Sharing:  NHGRI is also committed to the timely release of open source software and well-documented data analyses. The current ENCODE Project is working under a Software and Analysis Release Policy for Consortium members that encourages the timely release of stable software and data analyses to maximize the value of ENCODE resources to the research community and to enhance the reproducibility of its work.  Software and analyses are expected to be well-documented and made available on version-controlled public repositories (software) or accessioned and released through the ENCODE DCC.   Applicants should provide a plan for release of software and analyses, if applicable, in the application that is consistent with the current policy. 

After the initial review, NHGRI program staff will conduct an additional administrative review of the plan for sharing software and analyses, and may negotiate modifications of this plan with the prospective awardee.  The final negotiated version of the resource sharing plan will become a term and condition of the award of the cooperative agreement.

At the start of the next phase of ENCODE, the Consortium will review the current policy and the ENCODE Steering Committee will approve any updates, as appropriate; however, NHGRI expects that there will not be any significant change to this policy that will affect the rapidity with which software and analyses are released to the public.  Applicants should indicate their willingness to participate in the development of such a final plan and to accept it. 

Resource Sharing:  As the ENCODE Project is creating a community resource, NHGRI intends that, in addition to data, software and analyses, any physical resources, such as DNA clones and cell lines, generated by the ENCODE awards should be made rapidly available to the research community and that resource sharing plans should follow the same principles and spirit as data, software and analysis release plans. As demonstrated by previous genomics community resource projects, these resources are of high value to the broader biomedical research community in enabling scientific studies.  Since the cost and effort involved in generating the resources can be high, rapid dissemination of these resources would accelerate scientific exploration since individual researchers would not need to replicate such efforts. The applicant should provide specific plans for resource sharing and distribution in the application, if applicable.  After the initial review, NHGRI program staff will conduct an additional administrative review of the plan for sharing resources and may negotiate modifications of the resource sharing plan with the prospective awardee.  The final negotiated version of the resource sharing plan will become a term and condition of the award of the cooperative agreement.

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

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

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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

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

Post Submission Materials

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

Section V. Application Review Information
1. Criteria

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

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 there a strong scientific premise for the project? 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 New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the PD(s)/PI(s) and other key personnel have demonstrated experience in coordinating management and dissemination of genomic datasets and in working cooperatively in large, distributed scientific projects?

Has adequate leadership for the day-to-day project management activities, e.g., a project manager and sufficient PD(s)/PI(s) effort to serve the key proposed roles, been described?   

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?  Does the project efficiently use available tools and resources to accomplish the goals of the project? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

Does the applicant propose a clear plan for generating and making available a high quality and comprehensive Encyclopedia of functional DNA elements?

What is the likelihood that the proposed project will make a high quality and comprehensive Encyclopedia of functional DNA elements available to the research community in a readily accessible and usable format?

Does the applicant propose a Data Analysis Center that can transform data and facilitate analyses for genome-wide ENCODE data and work with data and metadata from a broad range of functional genomics projects?

Are the plans for specifying and updating uniform data processing pipelines from a broad range of functional genomics projects reasonable and appropriate?

Are the plans for developing and updating data quality metrics and standards for a broad range of functional genomics projects reasonable and appropriate?

What is the likelihood that the proposed project can effectively facilitate the integrative analysis of ENCODE data?

Are the plans for providing feedback to NHGRI and the consortium about the quality and utility of the ENCODE data reasonable and appropriate?

Are the plans to analyze consortium data to prioritize short-term and long-term data collection goals for ENCODE reasonable and appropriate?

Does the applicant propose a Data Analysis Center that will support activities of the ENCODE Analysis Working Group (AWG)?

Are the plans to work closely with the Data Coordination Center (DCC) to function as an integrated EDCAC reasonable and appropriate?

Are the plans to work with other Consortium members, including informatics components of individual research groups and the AWG, reasonable and appropriate?

Are the milestones, timelines, and goals proposed for the research project reasonable and appropriate?

Are the plans to disseminate the proposed Encyclopedia and relevant ENCODE analyses reasonable and appropriate?

Are the plans to identify and recruit groups with needed expertise for the analyses reasonable and appropriate?

Are the plans to track costs for computational infrastructure and personnel reasonable and appropriate?

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?  Is the computational infrastructure adequate to meet the needs of the project?         

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

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

Not Applicable

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

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).

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. 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 approaches, a diversity of experimental assays, a diversity of biological systems, a diversity of biological processes and diseases, throughput of the approaches, and whether the PD/PI will be  funded under other components of ENCODE through the companion FOAs.
  • Potential to work effectively in large collaborative efforts or research consortia.
  • Adequacy of data sharing, software sharing, data analysis sharing, and resource sharing plans as appropriate.
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 grantee’s business official.

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

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

After award selection but prior to funding, the prospective awardees for the DAC and DCC will be asked to submit revised budgets and research plans that account for the coordinated activities.  NHGRI program staff will be responsible for the administrative review of these revised budgets and plans for coordinated activities, and may negotiate modifications. The adequacy of the negotiated budgets and plans for the coordinated activities will be considered by program staff when making final funding recommendations.

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, Grantees, 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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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, 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 awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

  • Defining the details for the project within the guidelines of RFA HG-16-006 and for performing the scientific activities.
  • Analyzing the entire genome, or explain why that is not possible.
  • Fully participating in group activities, including working group and Consortium teleconference calls, attending periodic workshops to discuss the ENCODE Project's progress and coordinating publication of research results.
  • Serving as a member of the ENCODE Research Consortium Steering Committee.
  • Sharing results, including data, analyses, resources, and software, as appropriate and according to the release policies developed for and by this project.
  • Fully disclosing algorithms, software source code, and experimental methods to the other members of the Consortium for the purpose of scientific evaluation and use by other consortium members.
  • Not disclosing confidential information obtained from other members of the Consortium.
  • Adhering to NHGRI policies regarding intellectual property and other policies that might be established during the course of this activity.
  • Accepting and implementing the common guidelines and procedures approved by the Steering Committee, External Consultants Panel and NHGRI.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

An NIH Project Scientist is a scientist of the NHGRI extramural staff who will have substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards, including providing technical assistance, advice, and coordination for the ENCODE Project and its component parts.  It is anticipated that decisions in all activities will be reached by consensus of the ENCODE Research Consortium Steering Committee and that NIH staff will be given the opportunity to offer input to this process.  One NHGRI Project Scientist will participate as a member of the Steering Committee and will have one vote. They will participate with the other Steering Committee members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.

The Project Scientist will:

  • Assist and facilitate the group process and not direct it.
  • Participate with the other Steering Committee members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
  • Negotiate milestones, e.g., throughput, quality, cost goals, and biological samples with the awardees, as necessary.
  • Serve as a liaison, helping to coordinate activities among and for the awardees, including acting as a liaison to the NHGRI, and as an information resource about extramural genome research activities.
  • Coordinate the efforts of the entire ENCODE Research Consortium, including other participating groups not funded through this FOA.
  • Attend all Steering Committee meetings as a voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.  The Project Scientist must be informed of all major interactions of members of the Steering Committee.
  • Retain the option to recommend, with the advice of the External Consultants Panel, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed upon at the time of the award, fails to maintain the state of the art of the field or fails to comply with the Terms and Conditions of the Award. 
  • Report periodically on the progress of the ENCODE Project to the Director, Division of Genome Sciences and Director, NHGRI.
  • Provide relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions to serve on the External Consultants Panel.
  • Serve as a liaison between the Steering Committee and the External Consultants Panel, attending External Consultants Panel meetings in a non-voting liaison member role.
  • Serve on subcommittees of the Steering Committee and the External Consultants Panel, as appropriate.
  • Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action.
  • Provide advice in the management and technical performance of the investigation.
  • Assist in promoting the availability of the ENCODE and related resources developed in the course of this project to the scientific community at large.
  • Participate in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the ENCODE Research Consortium.
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NHGRI Project Scientist.

Areas of Joint Responsibility include:

The ENCODE Research Consortium Steering Committee will serve as the main coordinating board of the ENCODE Research Consortium established under this FOA and the accompanying RFAs HG-16-002, HG-16-003, HG-16-004, and HG-16-005.  The Steering Committee will be comprised of one P.D./P.I. from the DCC, DAC, each Mapping Center, and each Characterization Center, plus one NHGRI Program Staff member. Once formed, the Steering Committee will decide upon an organization and leadership structure and establish steering committee sub-committees. The Steering Committee may add additional members on an ad hoc basis, e.g., the P.D.s/P.I.s funded in response to RFA HG-16-004, “Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data".  Other government staff may attend the Steering Committee meetings if their expertise is required for specific discussions.  It is anticipated that additional coordination mechanisms will be set up with other U.S. and international groups that may join this effort.

The Steering Committee will be responsible for coordinating the activities being conducted by the ENCODE Research Consortium.  To address particular issues, the Steering Committee may establish working groups as needed, which will include representatives from the Research Consortium and the NHGRI and possibly other experts.  Such groups might include ones to: 1) develop a list of common biological samples and other reagents needed for the Project; 2) address data management issues; 3) analyze Project data; 4) develop quality standards and methods to assess data quality; and 5) handle communication issues and develop principles for reporting findings. Minutes of the Steering Committee meetings will be available to the Steering Committee members within 30 days after each meeting.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

An External Consultants Panel will be established by the NHGRI to evaluate the progress of the ENCODE Research Consortium.  The External Consultants Panel will provide recommendations to the Director, Division of Genome Sciences and Director, NHGRI about the progress and scientific direction of all components of the program.  The External Consultants Panel will be composed of five to eight senior scientists with relevant expertise, although the membership may be enlarged permanently or on an ad hoc basis as needed.

The External Consultants Panel will meet at least twice a year; some meetings may be conducted by telephone conference.  At least once a year, there will be a joint meeting with the Steering Committee to allow the members of the both the External Consultants Panel and the Steering Committees to interact directly with each other.  Twice a year the External Consultants Panel will make recommendations regarding progress of the ENCODE Research Consortium and present advice to the Director, Division of Genome Sciences and/or the Director, NHGRI about changes, if any, that may be necessary in the ENCODE Research Consortium program.

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 awardee. This special dispute resolution procedure does not alter the awardee'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, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)|
Telephone: 301-710-0267

Scientific/Research Contact(s)

Mike Pazin, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: pazinm@mail.nih.gov

Peer Review Contact(s)

Ken Nakamura, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8823
Email: nakamurk@mail.nih.gov 

Financial/Grants Management Contact(s)

Monika Christman
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: christmm@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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