Required Application Instructions

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

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

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

The purpose of this FOA is to solicit applications to develop and implement a Data Coordination Center (DCC) for the ENCyclopedia Of DNA Elements (ENCODE) project. The DCC will house, organize, and share metadata and data; process data from production groups; provide a portal to enable the community to visualize and download data; import data from projects and investigators outside of ENCODE; serve as the coordinating center for the ENCODE Consortium; and provide leadership for outreach to the scientific community. The DCC will work closely with all ENCODE components, and will work in conjunction with the Data Analysis Center (DAC), described in a companion FOA, to function as a single ENCODE Data Coordination and Analysis Center (EDCAC).

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.

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 this FOA and a Data Analysis Center (DAC) funded through RFA-HG-16-006. 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-16-006), as well as functional genomics data derived by groups operating outside the ENCODE consortium. As the identity of the funded projects will not be known at the time that 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 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. 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 Coordination Center (DCC) component of the EDCAC. The DCC will:

• manage the uptake, quality control, and accessioning of data, metadata, tools, and analyses from all members of the ENCODE Consortium, as well as relevant functional genomics data generated outside of the consortium
• provide a portal to allow the community to visualize and download data, tools and analyses
• serve as a coordinating center for consortium activities
• lead consortium outreach efforts

The Data Analysis Center (DAC), described in the companion FOA RFA-HG-16-006, will initiate and lead integrative analyses. 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 essential 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. 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 components of the EDCAC should be flexible in their implementation of data management and analysis workflows.

The data management needs of the ENCODE Project will include tracking, storing, and providing access to primary data from multiple experimental methods, as well as to processed data from a variety of computational methods; both primary and processed data are used in the identification of genomic functional elements. Specifically, for each experimental platform used, there will be several levels of data produced that represent different steps in the analysis. Level 1 data are the primary data from a particular experimental platform, Level 2 data are the processed primary data, and Level 3 data are the interpreted data that define candidate functional elements. In some situations, integration of multiple datasets results in generation of Level 4 data, or summary data, that define a distinct set of candidate functional elements in the genome. As an example, for a ChIP-seq experiment designed to define binding sites for a transcription factor, the sequence reads of the immunoprecipitated DNA are the Level 1 data, the reads aligned to the genome are the Level 2 data, the called peaks and signal tracks are the Level 3 data, while Level 4 data are predictions of promoters based on integration of transcription factor binding and chromatin modification profiles.

It is expected that applicants will be capable of working with data, metadata, and analyses from all members of the ENCODE Consortium. These are essential elements of the DCC:

1) Production data and metadata submission pipelines.

The DCC will provide submission pipelines for all data (Levels 1-4) and metadata generated by the ENCODE Consortium. The DCC will provide mechanisms and staff to interact with the data production groups to facilitate the timely and efficient transfer of data and metadata to the DCC.

2) Uniform processing of data.

The DCC will implement and run data processing pipelines for the ENCODE assays. These pipelines will be specified collaboratively by the data production groups, the DAC, and the DCC. The pipeline output will be the official processed data from the consortium. The pipelines and the pipeline descriptions will be shared with the community, to enhance reproducibility and transparency, and also to allow the community to use the pipelines (or modified versions). Pipeline output will include quality metrics, as well as a description of software versions and parameters.

3) Community data and metadata submission pipeline.

The DCC will establish a submission pipeline through which investigators and projects outside of the funded ENCODE groups may submit functional genomics data and associated metadata. The pipeline will include procedures to track and store data provenance and include quality assurance steps so that community data accessioned at the DCC meets minimum ENCODE data and metadata standards. The DCC will also import other relevant functional genomics data, as identified by the ENCODE Analysis Working Group (AWG) or the NHGRI.

4) Database.

The DCC will provide data management and retrieval tools capable of handling all of the ENCODE data, metadata, analyses, and computational tools, including those from previous phases of ENCODE and related functional genomics projects, as well as highly-relevant community data and associated metadata. The database provided should be robust, flexible, extensible, scalable, and capable of housing all primary data, metadata, and processed data for the duration of the project period. The data and metadata will be available in standard formats to foster interoperability. The primary data will be maintained at the DCC and be accessible to the community for the duration of the project.

5) Data Analytics.

The DCC will regularly report to NHGRI and the consortium on data submission, processing, and release. This will include data from Mapping and Functional Characterization groups funded through the companion FOAs (RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, and RFA-HG-16-006) as well as data submitted from outside the consortium. This information will provide strategic data-based prioritization of scientific areas in need of data generation, in real time.

6) ENCODE Portal.

Efficient and unencumbered access to the ENCODE data will be provided by the DCC though the development and maintenance of an ENCODE Portal. The ENCODE Portal will be the primary location for the community to access ENCODE data prior to and after publication. This data portal will need to serve the broad scientific community with a wide range of expertise in informatics, biology, and disease. The current ENCODE portal can be found at https:/www.encodeproject.org.

7) Export pipeline.

The DCC will establish an export pipeline to transfer any ENCODE data used in publications to other public repositories and community databases.

8) Consortium coordination center.

The DCC component will have primary responsibility for facilitating communication and coordination within the consortium, including organizing and supporting consortium working groups and an annual consortium meeting.

At the start of the project, the DCC will seamlessly maintain access to data and resources from the current ENCODE DCC. The DCC will maintain backwards compatibility with existing ENCODE data, metadata, and analyses. In addition to data generated by the data production centers, the DCC will import other relevant functional genomics data, as identified by the ENCODE Data Analysis Center, Analysis Working Group (AWG) or the NHGRI, such as data from IHEC or new NIH-funded programs, that will aid in the identification of a comprehensive set of functional elements in the genome. At the end of the project, the DCC will be able to transfer the ENCODE Project data to any other informatics resource, as designated by the NHGRI.

The efforts of the DCC should be focused on collecting, tracking, and distributing relevant information for the ENCODE Project, and should not duplicate the informatics efforts of other projects that have been funded for analysis of ENCODE data, especially the analysis activities supported by the companion FOAs (RFA-HG-16-002, RFA-HG-16-003, RFA-HG-16-004, RFA-HG-16-006). However, as the analysis needs of the Consortium change with time, the DCC may be asked to implement certain analysis pipelines as agreed upon by the ENCODE AWG.

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 (UM1) , to support characterization of candidate functional elements, RFA-HG-16-004 Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data (U01) , to support additional analysis activities, and RFA-HG-16-006, ENCODE Data Analysis Center (U24) , to support the analysis activities of ENCODE, 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. In addition, 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 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: http://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.

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.

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) 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 allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date 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.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

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

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

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

Applicants must 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.

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

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

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

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

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

The letter of intent should be sent to:

Mike Pazin, Ph.D.
Telephone: 301-496-7531
Fax: 301-480-2770
Email: [email protected]

Please transmit Letter of Intent by email to [email protected].

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.

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

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

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

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

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

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

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 support for annual Consortium meetings with approximately 150 participants to cover cost of meeting facilities and logistics, food for participants, and travel and accommodations for 5 members of the External Consultants Panel.

Budgets should include support for annual Users meeting with approximately 250 participants to cover cost of meeting facilities and logistics and travel for speakers; budgets should also include support of other tutorials, as appropriate.

Budgets should include costs for monthly Consortium calls for 100 participants and 10 bi-weekly working group calls for 20 participants each.

The ENCODE Project has regular conference calls and meetings. Applicants should request funds for 2-6 group members to attend annual meetings and to attend Consortium-led tutorials, as appropriate.

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

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

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

Research Strategy: Applicants should describe plans for a DCC that is capable of working with data, metadata, and analyses from all members of the ENCODE Consortium. Applicants should address the following points in the application:

1) Description of production data and metadata submission pipelines.

Applicants should describe submission pipelines for all data (Levels 1-4 as described above) and metadata generated by the ENCODE Consortium, including in their description:

• Plans for interacting with the data production groups to facilitate the timely and efficient transfer of data and metadata to the DCC.
• Plans to employ unique identifiers to enable subsequent tracking of the provenance for submitted data of all types.
• Plans for monitoring the quality of the data and metadata and developing quality assurance methods to ensure that the data meet the relevant data standards established by the ENCODE Consortium. (For standards established by previous phases of the ENCODE Project see https://www.encodeproject.org/data-standards/.)
• Plans for releasing data and metadata produced by the consortium to a DCC public data portal (see below) in a timely fashion.
• Plans to interact with the other members of the ENCODE Consortium to establish the exact types and formats of data that will be transferred to the DCC and develop procedures to track the quality metrics for the incoming data.
• Plans to define the appropriate experimental metadata to be submitted with each dataset (including, e.g., information on cell and tissue types, experimental conditions, affinity reagents, protocols, descriptions of how data were processed), along with associated controlled vocabularies.
• Plans to submit metadata using well-defined formats and, where available, established ontology terms (e.g., http://www.bioontology.org; description of ontologies currently employed at the ENCODE DCC are available at https://www.encodeproject.org/help/getting-started/#organization).
• Plans to track and store the data provenance (for each data level) that is needed to enhance transparency and reproducibility of analyses.

2) Description of pipelines for uniform processing of data.

Applicants should describe:

• Plans for implementing and running data processing pipelines (which will be specified collaboratively by the data production groups, the DAC, and the DCC) for the assays employed by the ENCODE Consortium.
• Plans for sharing pipeline descriptions with the community to enhance reproducibility and transparency, and also to allow the community to use the pipelines.
• Plans for including quality metrics and descriptions of software versions and parameters in pipeline output.

3) Description of pipelines for community data and metadata submission.

Applicants should describe:

• Plans to establish a submission pipeline through which investigators and projects outside of the funded ENCODE groups may submit functional genomics data and associated metadata.
• Procedures to track and store data provenance and include quality assurance steps so that community data accessioned at the DCC meets minimum ENCODE data and metadata standards.
• A strategy to import other relevant functional genomics data, as identified by the ENCODE Analysis Working Group (AWG) or the NHGRI.

4) Description of database.

Applicants should describe:

• Plans to provide data management and retrieval tools capable of handling all of the ENCODE data, metadata, analyses, and computational tools, including those from previous phases of ENCODE and related functional genomics projects, as well as highly-relevant community data and associated metadata.
• A strategy for making the database robust, flexible, extensible, scalable, and capable of housing all primary data, metadata, and processed data for the duration of the project period.
• Plans to make data and metadata available in standard formats (for formats currently employed by ENCODE, see https://www.encodeproject.org/help/file-formats/ and https://www.encodeproject.org/help/rest-api/ ).

5) Plans for providing data analytics.

Applicants should describe:

• Plans to regularly report to NHGRI and the ENCODE Consortium on data submission, processing, and release (including data from Mapping and Functional Characterization groups funded through the companion FOAs as well as data submitted from outside the consortium) in order to provide strategic data-based prioritization of scientific areas in need of data generation, in real time.

6) Plans for an ENCODE Portal.

Applicants should describe plans to provide efficient and unencumbered access to the ENCODE data though the development and maintenance of an ENCODE Portal. The ENCODE Portal will be the primary location for the community to access ENCODE data prior to and after publication, and should serve the broad scientific community with a wide range of expertise in informatics, biology, and disease. Applicants should describe their vision for a portal featuring multiple mechanisms for delivering data about functional elements in the relevant genome(s) including:

• A website that describes all of the data available for the ENCODE Project with links to descriptions of the data including any metadata associated with an experiment;
• A state-of-the-art genome browser view of ENCODE data and the candidate functional elements identified by the ENCODE Consortium, including the ability to search for elements linked to particular genes or genomic loci;
• Metadata-enabled querying of the data to identify subsets of the data. The portal should leverage existing informatics projects for this purpose;
• Application Programming Interfaces (APIs) or web services for programmatic access to the data;
• A method(s) to download freely large datasets from the portal so that users can acquire and analyze all or large parts of the data, and;
• Appropriate social media outlets for information about the ENCODE Project.
• The applicant should describe plans to evaluate the usability of the portal and other capabilities of the DCC that serve its user communities, including the data production groups and outside users representing a diverse range of expertise in informatics, biology, and human disease. This plan should describe the frequency of these evaluations and how this information will be used to improve on the utility of the DCC to the user community.

7) Description of an export pipeline.

Applicants should describe:

• Plans to develop an export pipeline to transfer any ENCODE data used in publications to other public repositories and community databases (e.g. Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI), ArrayExpress at the European Bioinformatics Institute (EBI), the UCSC Genome Browser at the University of California at Santa Cruz, and Ensembl at the EBI and the Wellcome Trust Sanger Institute) no later than submission of a manuscript for publication by the Consortium or its individual members.
• Plans to provide links between the data in the public repositories and the data as they reside in the DCC.
• Plans to interact with community informatics resources such as the Mouse Genome Database (MGD) to ensure the relevant mouse data are shared with these resources in a timely manner.
• Plans to establish a software repository to store and disseminate software developed by the ENCODE Consortium.

8) Plans to function as the ENCODE Consortium coordination center.

Applicants should describe:

• A strategy for serving as the communication and coordination center within the consortium, including organizing and supporting consortium working groups and an annual consortium meeting.
• Plans to provide internet-based resources such as mailing lists, a wiki, and social media tools to share data and enable discussions within the consortium.
• A strategy for outreach activities that will help make ENCODE resources as widely accessible and highly utilized as possible (e.g., tutorial sessions, community workshops, online training resources, update announcements to the community).

Additional information applicants should describe in the application:

• Plans to seamlessly maintain access to data and resources from the current ENCODE DCC, including maintaining backwards compatibility with existing ENCODE data, metadata, and analyses.
• A strategy to import other relevant functional genomics data, as identified by the ENCODE Data Analysis Center, Analysis Working Group (AWG) or the NHGRI, such as data from IHEC or new NIH-funded programs, which will aid in the identification of a comprehensive set of functional elements in the human and mouse genomes.
• Plans to transfer the ENCODE Project data to any other informatics resource, as designated by the NHGRI.
• Plans to make data and metadata submitted to the DCC rapidly available at the ENCODE Portal (within two weeks of receipt by the DCC), and to rapidly submit data to public repositories and community databases (no later than submission of a manuscript), in order to make available stable, high quality ENCODE datasets, including the final analysis datasets.
• Plans for prioritizing activities to ensure that the main goal of ENCODE, to generate an Encyclopedia of functional elements, will be achieved, including consideration that 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, and that 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.
• Plans to support and, where necessary, provide training for consortium members who will interact with the DCC, who may have varying levels of bioinformatics skills.
• Plans to work with data on the human and mouse genomes.
• 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.
• Plans to leverage existing software projects, where applicable.
• Plans to employ standard formats for data input and output, to facilitate its use and interoperability with other software (preferably formats already are in use by the Consortium; if new standard formats are needed, they should be developed in close collaboration with the ENCODE AWG).

Awardees funded in response to this FOA will be expected to coordinate their funded activities with the ENCODE DAC. As the identity of the DAC will not be known until the awards are funded, it will be necessary for applicants to describe in general terms how they will interact with the DAC.

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

• Evidence of Successful Past Performance. Applicants should provide evidence of research productivity as a data coordinating center and/or data analysis center in previous or ongoing genomics research networks. Applicants should demonstrate the 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, per research group submitting data, and 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.
• Information Technology (IT). Applicants should discuss all pertinent informatics issues involved in providing the basic IT infrastructure/system administration for the proposed project.
• Technology Development. Incremental technology improvements will play an important role in increasing the efficiency and decreasing the cost of the DCC. 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 DCC, without disrupting access to the resource. Any needed software development to implement these technology development activities should be described in detail.
• Management Plan. The management plan should describe how the PD(s)/PI(s) will manage the proposed project, 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. Useful elements of this description include the organization of the proposed project; its management structure, including the integration of the DCC and DAC; key personnel; 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 and timeline for the DCC, and annual milestones with metrics that will document progress towards the achievement of the ultimate goals. Examples include, but are not limited to, milestones that track 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.

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

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

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

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.

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

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

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? 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?

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?

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?

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?

Are pipelines described to import, store, and disseminate ENCODE data and metadata, and relevant data and metadata from the research community outside of the ENCODE consortium?

Are the plans to import, store, and disseminate the relevant ENCODE data and metadata in a timely manner reasonable and appropriate?

Are the plans to import, store, and disseminate relevant functional genomics data and metadata from the research community outside of the ENCODE consortium reasonable and appropriate?

Are the plans for tracking the provenance of submitted data reasonable and appropriate?

Are the plans for providing APIs or web services for programmatic access to ENCODE data reasonable and appropriate?

Are the plans for employing standard file formats and established ontologies reasonable and appropriate?

Are the plans to work closely with the DAC to function as an integrated EDCAC reasonable and appropriate?

Are the plans to implement and run uniform data processing pipelines, and to work closely with the DAC and data producers to specify pipelines, 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 plans for providing a portal for the efficient release of resources and data, including evidence that systems are in place to support data release, reasonable and appropriate?

Is the pipeline described for exporting ENCODE data and metadata to relevant public databases reasonable and appropriate?

Are the plans to provide data analytics and to regularly report to NHGRI and the consortium on data and metadata submission, processing, and release, reasonable and appropriate?

What is the likelihood that the proposed center can effectively track the progress of ENCODE activities?

Are the plans to integrate or link to data from other human genome resource efforts in the U.S. and abroad reasonable and appropriate?

Are the plans for the release or distribution of other resources, software, or technologies developed under this award reasonable and appropriate?

Are the plans for maintaining access to existing ENCODE data and resources reasonable and appropriate?

Are the plans for leading consortium outreach efforts reasonable and appropriate?

Are the plans for serving as a coordinating center for consortium activities reasonable and appropriate?

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

Are the plans for training and providing support to users of the EDCAC with different levels of bioinformatics skills reasonable and appropriate?

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

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?

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

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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.

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.

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 DCC and DAC 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.

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-16-005 and for performing the scientific activities.
• Providing annual and overall project period milestones for throughput, to the NHGRI as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by NHGRI program staff).
• 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-16-006. 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.

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

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

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

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

eRA 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)
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GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
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Telephone: 301-710-0267

Mike Pazin, Ph.D.
National Human Genome Research Institute (NHGRI
Telephone: 301-496-7531
Email: [email protected]

Ken Nakamura, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8823
Email: [email protected]

Monika Christman
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: [email protected]

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

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