Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Human Genome Research Institute (NHGRI)
Funding Opportunity Title	Data Analysis and Coordination Center for the Encyclopedia of DNA Elements (ENCODE) (U41)
Activity Code	U41 Biotechnology Resource Cooperative Agreements
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-HG-11-026
Companion FOA	RFA-HG-11-024, U54 Specialized Center- Cooperative Agreements RFA-HG-11-025, U01 Research Project Cooperative Agreements
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.172
FOA Purpose	The Encyclopedia of DNA Elements (ENCODE) and modENCODE projects have, over the past eight years, cataloged a significant fraction of the functional elements in the genomes of the human and three well-studied model organisms, and these catalogs are increasingly being used by the research community to expand on basic biological knowledge and to interpret the results of disease-mapping studies. The National Human Genome Research Institute (NHGRI) solicits applications to develop and implement an ENCODE Data Coordination and Analysis Center (EDCAC) as part of the continuation of the ENCODE Project. The EDCAC will have two components: (1) a Data Coordination (DC) component to develop, house, and maintain databases to track, store, and provide access to the data generated by the ENCODE Project, and (2) a Data Analysis (DA) component to coordinate and assist in the integrative analysis of data produced by the ENCODE Consortium. This FOA solicits applications for both components, which will be funded separately. Applicants responding to this FOA may apply for either one or both of the EDCAC components, but separate applications will be required for each. An applicant may not submit a single application that combines the two components. The funded projects will then be expected to coordinate their activities to function as a single EDCAC, and to participate in the ENCODE Research Network that will be a consolidation and continuation of the existing ENCODE and modENCODE Research Consortia.

Posted Date	October 4, 2011
Letter of Intent Due Date	November 21, 2011
Application Due Date(s)	December 21, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	March, 2012
Advisory Council Review	May , 2012
Earliest Start Date(s)	July, 2012
Expiration Date	December 22, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of 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

Purpose

The Encyclopedia of DNA Elements (ENCODE) and modENCODE projects have, over the past eight years, cataloged a significant fraction of the functional elements in the genomes of the human and three well-studied model organisms, and these catalogs are increasingly being used by the research community to expand on basic biological knowledge and to interpret the results of disease-mapping studies. The National Human Genome Research Institute (NHGRI) solicits applications to develop and implement an ENCODE Data Coordination and Analysis Center (EDCAC) as part of the continuation of the ENCODE Project. The EDCAC will have two components: (1) a Data Coordination (DC) component to develop, house, and maintain databases to track, store, and provide access to the data generated by the ENCODE Project, and (2) a Data Analysis (DA) component to coordinate and assist in the integrative analysis of data produced by the ENCODE Consortium. This FOA solicits applications for both components, which will be funded separately. Applicants responding to this FOA may apply for either one or both of the EDCAC components, but separate applications will be required for each. An applicant may not submit a single application that combines the two components. The funded projects will then be expected to coordinate their activities to function as a single EDCAC, and to participate in the ENCODE Research Network that will be a consolidation and continuation of the existing ENCODE and modENCODE Research Consortia. 

This FOA will use the U41 Biotechnology Resource Cooperative Agreement mechanism. It is being issued in conjunction with two other FOAs: RFA-HG-11-024 Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms (U54) , and RFA-HG-11-025, Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data (U01) .

Background

The long-term goal of the Encyclopedia of DNA Elements (ENCODE) Project has been to identify comprehensively all of the sequence-based functional elements in the human genome. The modENCODE Project is a parallel effort to annotate the genomes of worm (C. elegans) and fly (D. melanogaster) comprehensively. In addition, with funds from the American Recovery and Reinvestment Act (ARRA) of 2009, a small, two-year effort was supported to generate comparable data from the mouse (M. musculus) to facilitate the annotation of the human genome. For the purpose of this solicitation, these efforts will collectively be referred to as the ENCODE projects. These projects have been designated as community resource projects by NHGRI to accelerate access to and use of the data by the entire scientific community. Accordingly, pre-publication data is released rapidly to public databases. For more information about the ENCODE projects, see: http://www.genome.gov/ENCODE.

Functional elements that have been elucidated in the ENCODE projects include transcribed sequences, transcriptional control elements (including enhancers, promoters, and insulators), chromatin features, and regulatory elements acting at the RNA level post-transcriptionally (including those that may regulate splicing, translation, and stability). Using a variety of high-throughput methods, such as RNA-seq, ChIP-seq, RIP-seq, and DNase-seq, these functional elements have been identified by mapping different types of marks, including transcription factor binding sites, histone modifications, various measures of chromatin structure, sites where RNA-binding proteins bind, and different classes of transcribed sequences. These growing catalogs of functional elements are directly adding to our general understanding of genome structure and function, and also are enabling targeted research projects to examine the role of these elements in the regulation of genes of interest and in specific biological processes. As genetic and epigenetic variation at these elements are undoubtedly responsible for some observed phenotypes, comprehensive identification of functional elements is also expected to enhance our understanding of human health and disease.

Currently, several different levels of data analysis are being conducted within the ENCODE projects. Each data production center has an analysis pipeline to process the primary data, to use particular data types to identify one or more specific classes of functional elements, and to identify any biological insights from these data. The data producers also process the data to prepare them for submission to a Data Coordination Center (DCC). There are two DCCs, one for ENCODE (http://www.encodeproject.org) and one for modENCODE (http://www.modencode.org), that are responsible for developing, housing, and maintaining databases to track, store, and provide access to the ENCODE and modENCODE data, respectively. Finally, each consortium has an Analysis Working Group (AWG) that is responsible for integrative analyses of the entire data sets of the respective projects. Supporting each AWG is a Data Analysis Center (DAC) that coordinates the high-level analytical activities and provides computational support for these analyses.

Each of the ENCODE projects has functioned as a research consortium that brings the participants together in a highly collaborative and synergistic effort. For the last four years, the ENCODE projects have focused on the comprehensive analysis of a limited set of common cell types, mainly cell lines, along with a survey of functional elements in other cell types. Analyses that have integrated the datasets within and across a variety of cell types for a given organism have amplified the amount of useful information that has been derived from the data (See: Nature 447:799-816, 2007; Science 330:1775-1787, 2010; Science 330:1787-1797, 2010; PLoS Biol 9:e1001046, 2011). The use of multiple cell types and multiple assays is, in fact, key to obtaining a comprehensive description of the functional elements in these genomes, as there is no one cell type or type of assay that can be used to identify all functional elements.

The NHGRI proposes to solicit applications for projects to extend the ENCODE projects with a new set of FOAs. For data production, RFA-HG-11-024 Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms (U54) solicits applications for projects to conduct high-throughput data-generation efforts that will significantly extend towards completion the current catalogs of sequence-based functional elements in the human, mouse (M. musculus), as well as possibly the fly (D. melanogaster) and worm (C. elegans) genomes. A companion FOA, RFA-HG-11-025 Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data (U01) , solicits applications to support analysis of the ENCODE data. With this FOA (RFA-HG-11-026), NHGRI solicits applications for projects to establish an ENCODE Data Coordination and Analysis Center (EDCAC). This EDCAC will support the data management and analysis activities for the next phase of the ENCODE Project.

Research Scope

The EDCAC will be an integrated, stable resource that will gather data and metadata from the ENCODE Project, provide analysis expertise and capacity to facilitate the ENCODE Project’s integrative analyses, integrate those data with the genome sequence, and serve as an informatics resource from which the community can readily access ENCODE data, analyses and methods. Because different skills and expertise are needed to conduct these activities, this FOA solicits applications for two distinct components of the EDCAC. One component will provide the data management functions, while the other will provide data analysis activities; these components correspond to the DCCs and DACs, respectively, of the current ENCODE projects. Once awards are made, the awardees will be expected to work together as a highly coordinated team to provide a single, integrated EDCAC.

Both components of 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-11-024 Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms and RFA-HG-11-025 Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data . 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, applicants should 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 the data being produced in the current human ENCODE Project was published recently (PLoS Biology 9:e1001046, 2011) and information about the most current data available for the project can be found on the ENCODE preview browser at UCSC (http://genome-preview.ucsc.edu/cgi-bin/hgTracks?db=hg19). A description of the modENCODE data can be found in that project’s marker paper, along with recent integrative papers describing the integrated analysis of data from the current modENCODE Project (See: http://www.genome.gov/26524507 - al-2 and http://www.modencode.org).

The data management needs of the ENCODE Project will include handling both primary data from multiple experimental methods and processed data from a variety of computational methods, both of which 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 the 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 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, and the called peaks are the Level 3 data. Level 4 data would be predictions of promoters based on integration of transcription factor binding and chromatin modification profiles.

In this next phase, the goal of the ENCODE Project will be to generate as comprehensive a catalog of functional elements as can be obtained using existing technologies as a resource to enable the broader scientific community to seek new advances in both basic and clinical knowledge. The next phase of data production for ENCODE will have a primary emphasis on annotating the human genome, a secondary emphasis on the mouse genome and possibly a significantly reduced and scientifically more restricted effort for the fly and worm genomes. The goal will be to generate catalogs of functional elements using high-throughput methods that define features of the genome such as gene models, open chromatin, 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, RIP-seq, and DNase-seq. Activities in the mouse will take advantage of this model system to assay additional cell types not easily obtained in humans. Additional work on the fly or worm genomes may be supported to improve on the annotation of these genomes. See RFA-HG-11-024 for more details.

Data Coordination Component

Applicants should describe plans for a Data Coordination (DC) component that is capable of working with data from all members of the ENCODE Consortium who will be generating data for functional elements in the human, mouse, worm, or fly genomes. This DC component must coordinate with the other analysis component funded in response to this FOA to form the EDCAC (see below).

The key elements for the DC component are described below.

1) Production data submission pipeline. A submission pipeline for all data (Levels 1-4) and metadata generated by the ENCODE Consortium must be described. The DC component must provide mechanisms and staff to interact with the data production groups to facilitate the timely and efficient transfer of data and metadata to the EDCAC. Each submitted dataset must be assigned a unique identifier that enables subsequent tracking for submitted data of all types (Levels 1-4). This pipeline must include quality assurance steps to monitor the quality of the submitted data and metadata, along with steps to release these data and metadata to an EDCAC public data portal in a timely fashion. The ENCODE Consortium has developed quality assurance methods to ensure that the data meet the relevant data standards established by the Consortium (see http://www.encodeproject.org/ENCODE/dataStandards.html). To implement this pipeline, the DC component must work with the other members of the ENCODE Consortium to establish the exact types and formats of data that will be transferred to the EDCAC and develop procedures to track the quality metrics for the incoming data. Similarly, the DC component must work with the ENCODE Consortium to define the minimum amount of experimental metadata required to be submitted with each dataset, along with associated controlled vocabularies. The metadata must be submitted using well-defined formats such as MAGE-TAB and, where available, established ontology terms (http://www.bioontology.org). This submission pipeline must include procedures to track and store the data provenance for the different levels of data (1-4) generated by the data producers and data analysts that must be captured to enhance transparency and reproducibility of the analyses.

2) Ancillary data submission pipeline. A separate submission pipeline must be described for ancillary data and information to support the ENCODE Consortium, including information on cell types and antibodies, standard protocols, and data generated as a result of technology development, platform characterization, studies to examine biological relevance by the data production centers, and Consortium publications.

3) Database. The DC component must provide robust and flexible data management and retrieval tools capable of handling all of the ENCODE data and metadata that will be stored at the EDCAC. The ENCODE data and metadata must be stored in a robust database capable of containing all of the primary data, metadata, and processed data for the duration of the ENCODE Project. Within the database, data and metadata must be available in standard formats to facilitate additional analysis by members of the Consortium and by the broader scientific community. The primary data must be maintained at the EDCAC and be accessible to the community for the duration of the project.

4) ENCODE Portal. Efficient and unencumbered access to the ENCODE data at the EDCAC will be provided though the development of an ENCODE Portal. The ENCODE Portal will be the primary location for the community to access ENCODE data prior to publication. This data portal will need to serve the broad scientific community with a range of bioinformatics expertise, ranging from bioinformaticians familiar with working with these data to more na ve users. Therefore, this portal should feature 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 a description of the data including any metadata associated with an experiment;
• A genome browser view of the functional elements identified by the ENCODE Consortium;
• Metadata-enabled querying of the data to identify subsets of the data. The EDCAC should leverage existing informatics projects for this purpose;
• APIs (application programming interfaces) or web services for programmatic access to the data;
• A method to download freely large datasets from the EDCAC 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 ENCODE Portal and other capabilities of the DC component that serve the user communities, including the data production groups and outside users representing both bioinformaticians and users unfamiliar with these data. This plan should describe the frequency of these evaluations and how this information will be used to improve on the utility of the EDCAC to the user community.

5) Export pipeline. The DC component will establish an export pipeline to transfer any ENCODE data used in publications to other public repositories and community databases no later than submission of a manuscript for publication by the Consortium or its individual members. These repositories may include the 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. The DC component must be able to provide links between the data in the public repositories and the data as they reside in the EDCAC. The DC component must interact with community informatics resources like the Mouse Genome Database (MGD), FlyBase and WormBase to ensure the relevant data on model organisms are transferred to these resources in a timely manner. In addition, the DC component will establish a software repository to store and disseminate software developed by the ENCODE Consortium.

Additional information:

The EDCAC is expected to be a key part of the ENCODE Consortium and work to facilitate the analyses of the data. The DC component will be expected to provide internet-based resources such as mailing lists, a wiki, or social media tools to share data and enable discussions within the Consortium. For data tracking, the DC component must provide real-time tracking of submitted and released datasets. Upon publication of data from the Consortium, the DC component must provide a public website containing links to the data and metadata, including workflows used to generate each analysis, for all figures in the paper.

At the start of the project, the EDCAC must copy data from the current ENCODE projects DCCs to the DC component funded in response to this FOA. In addition to data generated by the data production centers, the DC component must import other relevant functional genomics data, as identified by the ENCODE AWG or the NHGRI, such as data from the NIH Common Fund Epigenomics Project (http://roadmapepigenomics.org) or any 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 EDCAC must be able to transfer the ENCODE Project data to any other informatics resource, as designated by the NHGRI.

Data and metadata submitted to the EDCAC must be available at the ENCODE Portal within two weeks of receipt by the EDCAC of a complete submission package from the data producers. The submission and rapid release of the ENCODE data at the ENCODE Portal will satisfy the requirements of the ENCODE data release policy, while the submission of the data to public repositories and community databases no later than submission of a manuscript, as described above, will make available the stable, high quality ENCODE datasets, including the final analysis datasets, reported in the publications. The DC component will prepare monthly reports to the NHGRI that summarize the data submitted to EDCAC by the data production groups and the data released to the EDCAC public website.

The applicants should provide milestones with metrics that will allow assessment of progress towards achievement of the goals for the DC component. These metrics should describe the time to process submitted data for release to the EDCAC public website, development of any new software or websites, and submission of ENCODE data to other public repositories.

The efforts of the DC component 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 either the data analysis component of the EDCAC (see below) or the analysis activities, supported by the companion FOAs RFA-HG-11-024 and RFA-HG-11-025. However, as the analysis needs of the Consortium change with time, the DC component may be asked to implement certain analysis pipelines as agreed upon by the ENCODE AWG.

Data Analysis Component

The applicant should describe plans to establish a Data Analysis (DA) component for the EDCAC to provide an informatics resource that will support the activities of the ENCODE AWG by coordinating and facilitating integrative analyses of the ENCODE and related data. The EDCAC will be a member of the AWG and will work with the informatics components of the individual ENCODE data production centers and the AWG. The DA component will provide resources and coordination activities that will enable the ENCODE Consortium to provide the production of useful information about functional sequence elements in the human and select model organism genomes to the larger biomedical research community.

The DA component will support activities within the ENCODE AWG that include but are not limted 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 DA component 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-11-025 Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data .

The applicant should describe a broad plan for how the DA component will accomplish the goal of facilitating the work of the AWG, including a description of how the specific activities listed below 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 DA component will interact with the AWG, with the DC component of the EDCAC, and with the rest of the ENCODE Consortium. During the past four years, the ENCODE projects found it useful for the AWG to recruit outside investigators to participate in ENCODE analyses to provide essential expertise or resources needed for the 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.

As part of the EDCAC, the applicant should describe plans to provide feedback to the Consortium about the quality and utility of the ENCODE data. A component of the AWG 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.

Other projects such as the Common Fund Epigenomics Project (http://commonfund.nih.gov/epigenomics/) are generating data related to the ENCODE Project and future NIH-funded projects may do so as well. As the goal of the ENCODE Project is to provide a comprehensive catalog of functional elements, the applicant should describe a plan to identify these additional data and to use these data to improve on the end product of the ENCODE Project.

The activities of the DA should not overlap with either the local informatics activities of each production center or the other activities of the EDCAC, but should complement each of these informatics components.

The essential aspects of the EDCAC to be supported by the DA component should include but are not limited to:

• Coordinating with the DC component funded in response to this FOA to form the EDCAC;
• Collaborating with the ENCODE Consortium members, including the data producers funded under companion FOA RFA-HG-11-024 Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms (U54) , analysis groups funded under the companion FOA, RFA-HG-11-025 Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) Data (U01) and the AWG, to identify the types of analyses that must be performed to generate a comprehensive and accurate catalog of functional elements;
• When needed, identifying areas of expertise not represented in the AWG and inviting outside investigators to join in AWG analyses;
• Organizing data analysis workshops that bring together researchers from both inside and outside of the Consortium including the data producers, experts in data analysis, and experts in the biology of different classes of functional elements for face-to-face interactions to promote better data analysis;
• Planning and implementing regular conference calls to coordinate analyses;
• Coordinating with the DC component to provide support, including data transformations and preparation of data freezes, for any data analyses agreed upon by the AWG;
• Performing analyses agreed upon by the AWG that compare different datasets using a variety of statistical methods to identify correlations between different data types;
• Performing analyses requested by the NHGRI to assess the quality and coverage of the ENCODE data;
• Performing 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.
• Facilitating interactions between the AWG and ENCODE Consortium members or outside investigators to identify any additional datasets from outside of the ENCODE Consortium for use in integrative analyses;
• Providing reports to the ENCODE Consortium on the results from the integrative analyses;
• Providing milestones with metrics that will allow assessment of progress towards achievement of the goals for the DA;
• Interacting with the DC component and with other informatics resources to disseminate results from the AWG; and
• Working with the AWG in the preparation of manuscripts for publication by the ENCODE Consortium.

Shared elements for both the DC and DA components

The ENCODE Project will operate as a Research Consortium. The awardees funded through this FOA RFA-HG-11-026 and the companion FOAs (RFA-HG-011-024 and RFA-HG-011-025) will participate in this Research Consortium. The Research Consortium will also be open to all other academic, government, and private sector scientists interested in participating in an open process to facilitate the comprehensive annotation of the human genome. Awardees and additional personnel from each EDCAC component will be required to attend one Research Consortium meeting per year; applicants should request funds for this meeting.

The NHGRI has designated the ENCODE Project as a community resource project and ENCODE Consortium members, including awardees from this FOA, will be expected to abide by the ENCODE data policy (html://www.genome.gov/12513440). The EDCAC will be expected to make the ENCODE data and resultant analyses freely available to the scientific community in a timely manner such that data are released to the public ENCODE Portal within 2 weeks of submission and released to public repositories no later than the submission of Consortium manuscripts. Timeliness is particularly important because the NHGRI anticipates that there will be considerable interest on the part of non-Consortium members in analyzing the data as well. Currently, this policy addresses only the release and use of primary data and analyses used to discover functional elements in the genome. The NHGRI will revisit the current data release policy with awardees of this and companion FOAs and update it to include integrative analyses to ensure that the goals of the ENCODE Project and the interests of the NHGRI, along with those of the data producers and analysts, continue to be met (see Section IV.2).

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. The applicants should describe how they will prioritize their activities to ensure that the main goal of ENCODE, to generate a comprehensive catalog of functional elements, will be achieved.

As the data storage, analysis, and dissemination needs of the Consortium changes with time, either or both components of the EDCAC may be asked to implement certain modifications to their workflows as agreed upon by the ENCODE Consortium. Both components of the EDCAC should indicate their willingness to be flexible in their implementation of data management and analysis workflows.

The applicants should describe plans to work with data on the human, mouse, fly, and worm genomes. Since the emphasis of the next phase for the ENCODE Project will be on the human genome and, to a lesser extent, the mouse genome, plans to work with fly and worm data should leverage existing model organism resources.

Any software developed by the EDCAC that would be of value to the scientific community should be modular and include appropriate documentation, so that it can work as a stand-alone package. Software should not duplicate existing software with similar features and should leverage existing software projects as much as possible. The software should use standard formats for data input and output, to facilitate its use and interoperability with other software. Such standard formats will preferably be ones that already are in use by the Consortium; if new standard formats are needed, they should be developed in close collaboration with the ENCODE AWG.

As a Biotechnology Resource (U41), the applicant should describe a plan and allocate sufficient resources to provide outreach to the user communities to educate the community about the ENCODE Project and its data, along with guides for how to access and use the ENCODE data. This plan should include training both specialists and non-specialists to make the best use of the ENCODE Project data.  Examples include presentations, short courses, or symposia offered independently or in conjunction with scientific meetings attended by the user community; web-based tutorials; and user manuals and training guides that describe the features of the ENCODE Portal. 

Awardees funded in response to this FOA will be expected to coordinate their funded activities to form a single EDCAC. As the identity of the components of the EDCAC will not be known until the awards are funded, the applicants should describe in general terms how they will interact with the other component of the EDCAC. In the circumstance where the PI is the same for both the DC and DA components, then the application can describe specific interactions between the two components.

After award selection but prior to funding, the prospective awardees for the EDCAC components will be asked to submit revised budgets and research plans that account for the coordinated activities, such that the different components can function as a single EDCAC. 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.

Applicants responding to this FOA may apply for either one or both of the EDCAC components, 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.

Funding Instrument	Cooperative Agreement
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NHGRI intends to commit $5.5 million in total costs in FY 2012 and to make two awards, one for each type of component.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	The total project period for an application submitted in response to this FOA may not exceed 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.

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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.

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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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 research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Peter Good, Ph.D.
Program Director, Genome Informatics
Division of Extramural Research
National Human Genome Research Institute (NHGRI)
5635 Fishers Lane, Ste. 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-496-7531
FAX: 301-480-2770
E-mail: goodp@mail.nih.gov
Please transmit Letter of Intent by email to goodp@mail.nih.gov.

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Ken Nakamura, Ph.D.
Scientific Review Officer
Scientific Review Branch
National Human Genome Research Institute (NHGRI)
5635 Fishers Lane, Ste. 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-402-0838
FAX: 301-435-1580
E-mail: nakamurk@mail.nih.gov

All page limitations described in the PHS398 Application Guide and must be followed, with the following exceptions or additional requirements:

• Research Strategy section is limited to 30 pages.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The following items must be addressed satisfactorily for an applicant to be eligible as a component of the EDCAC:

Evidence of Successful Past Performance. Applicants must provide evidence of research productivity as a data coordinating center/data analysis center in previous or ongoing genomics research networks. Applicants must 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, if necessary, for personnel responsible for working with the data producers on data submission (data wranglers). 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.

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 both components for the EDCAC. 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 EDCAC components. Any needed software development to implement these technology development activities should be described in detail.

Management Plan and P.I. Effort. The effective management of each EDCAC component requires a significant commitment by the Principal Investigator (P.I.). The P.I. of a project funded under this FOA must devote at least 25% effort (3 person months) to that component. The applicant should describe how s/he will manage the proposed project, who will oversee the day-to-day activities (e.g., a project manager if not the P.I.) 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 separate parts to form an efficient component of the EDCAC; 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 for the proposed project, either the DC or DA component, and annual milestones with metrics that will document progress towards the achievement of the ultimate goals. For each of the EDCAC components, 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 a 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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modifications:

• 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. The implementation of the concept of rapid, prepublication data release has evolved over time in response to the changing technological and scientific landscapes, as described in the report from a meeting held in Toronto in 2009 (http://www.nature.com/nature/journal/v461/n7261/full/461168a.html). Although the Toronto meeting report specifically did not use the earlier term community resource project, it did recommend that funding agencies should require rapid pre-publication data release for projects that generate data sets that have broad utility, are large in scale, are 'reference' in character and typically have community 'buy-in'.
• The ENCODE Project is one such project, and NHGRI will continue to consider it as a community resource project.  The ENCODE and modENCODE Consortia established and currently operate under a common Data Release Policy (see http://www.genome.gov/27528022), which expects rapid pre-publication data release. The current policy allows a nine-month moratorium period on presentations and publications, during which time data users may freely use the ENCODE and modENCODE data to design and carry out their own research programs, but are asked not to submit publications or make public presentations that use the unpublished ENCODE/modENCODE data without prior consent. The purpose of this moratorium period has been to allow the data producers to have an opportunity to publish on their initial findings. At present, after the nine-month moratorium, all data are freely available to anyone to use in any manner in presentations and publications. Agreement to abide by that policy is a requirement for anyone to join one of the Consortia. 
• NHGRI expects that the rapid data release principles of this policy will continue to be implemented during the next phase of the ENCODE Project. Applicants will be expected to propose a data release policy in their applications (see below) that addresses rapid data sharing with the community, consistent with achieving the goals of the project. However, NHGRI is concerned that the nine-month moratorium has not been achieving the goal of getting data to be used rapidly by the research community, and plans, at the start of the next phase of ENCODE, to raise for discussion amongst consortium members that there be no such moratorium. NHGRI’s rationale for such an approach is that while the utility of the ENCODE data is increasing, the data types themselves are no longer novel because of the maturation of both the ENCODE Project and the associated technologies. As a result, biological interpretation of the data, which is outside the scope of this initiative and which may take longer than nine months to complete, is increasingly being required for publication. A longer moratorium period to accommodate this would be inconsistent with the primary purpose of ENCODE to generate a high quality, comprehensive and broadly useful catalog of functional elements, and to make it available expeditiously to the research community. It is also NHGRI’s intent, going forward through this FOA, to fund fewer, more centralized, and higher throughput production centers that will not focus on specific biological studies beyond the minimum amount needed to validate the quality of the forthcoming data.
• Another issue that has arisen since the current ENCODE data release policy was developed is that of the pre-publication release of integrative data analyses from a community resource project. In situations where the analysis methods are stable and the Consortium thinks that the resultant analyses may be of value to the community, NHGRI believes that these analyses should also be rapidly released to the community prior to publication to further the advancement of research.
• Once the next phase of ENCODE begins, the ENCODE Consortium members will be asked to revisit the data release policy, consider the issues NHGRI has raised above and any other issues raised by the research community, and establish an updated data release policy as appropriate.
• Applicants should provide a specific proposal for release of production data in the application, and are encouraged to address the issue of the release of data analyses. The reasonableness of the proposed data sharing plan will be assessed by the reviewers who will provide their assessment of the proposed data sharing plan as an administrative note and will not factor it into the determination of scientific merit or the impact score. After the initial review, NHGRI program staff will be responsible for any additional administrative review of the plan for sharing data and may negotiate modifications of the data sharing plan with the prospective awardee before recommending funding of an application.  The adequacy of the negotiated data sharing plan will be considered by program staff when making funding recommendations.  The final negotiated version of the data sharing plan will become a term and condition of the award of the cooperative agreement with the expectation that the Consortium will develop a common plan for data release once the awards are funded, and that this common plan will be adopted by all awardees. 
• In summary, in considering data sharing, applicants should understand that NHGRI’s interest is for the ENCODE Consortium going forward to again have a common data release policy to which all participants in the Consortium will adhere. NHGRI will negotiate an interim data release plan as appropriate with each prospective awardee before an award is issued. After all of the awards have been made, the ENCODE Steering Committee, of which all awardees will be members, will develop a final, common data release plan as appropriate for the Project that will address the interests of the data producers and analysts, as well as the users of the ENCODE catalogs. Applicants should indicate their willingness to participate in the development of such final plan and to accept it.
• The effectiveness of data sharing will be evaluated as part of the administrative review of the annual non-competing Grant Progress Report (PHS 2590).
• See Section VI.3. Reporting.
• Resource Sharing: As the ENCODE Project is generating a community resource, NHGRI intends that, in addition to data, resources 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 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 of generating the resources can be high, rapid dissemination of these resources would accelerate scientific exploration since individual researchers would not have to replicate such efforts. The applicant should provide specific plans for resource sharing and distribution in the application.  The reasonableness of the proposed resource sharing plan will be assessed by the reviewers who will provide their assessment of the proposed plan as an administrative note and will not factor it into the determination of scientific merit or the impact score. After the initial review, NHGRI program staff will be responsible for any additional administrative review of the plan for sharing resources and may negotiate modifications of the resource sharing plan with the prospective awardee before recommending funding of an application.  The adequacy of the negotiated resource sharing plan will be considered by program staff when making funding recommendations. The final negotiated version of the resource sharing plan will become a term and condition of the award of the cooperative agreement. The effectiveness of the resource sharing plan will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590).  See Section VI.3. Reporting.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign (non-US) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHGRI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Additional information:

An Information Session for this FOA and related FOAs RFA-HG-11-024 and RFA-HG-11-025 will be held on October 31, 2011, from 12 noon-3 PM Eastern Daylight Savings Time. The Information Session will be conducted as a teleconference. No provisions will be made for in-person attendance. 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.

Prospective applicants who plan to participate in the Information Session should send an e-mail expressing their interest as soon as possible to NHGRI at encode@mail.nih.gov in order to receive logistical information about the Information Session, including dial-in numbers, which will be provided no later than October 27, 2011. In the Subject line of the e-mail request, please write: Information Session . The email message should contain:

            Name,
            Institution,
            E-mail address,
            Number of telephone lines that your group plans to use for the teleconference 

Prospective applicants are encouraged to submit their questions about the FOAs to encode@mail.nih.gov before October 27, 2011. Prospective applicants may ask additional questions during the Information Session, and NHGRI staff will respond to those questions. Following the Information Session, by November 4, 2011, the NHGRI will post a summary of questions and answers at http://www.genome.gov/ENCODE. Prospective applicants with inquiries concerning these FOAs who are unable to participate in the Information Session are encouraged to view the summary of questions and answers after they are posted. For any additional questions that are not addressed in the summary, please contact the program contacts listed in the FOAs for which you plan to apply.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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/priority 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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 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) have demonstrated experience in coordinating management and disemination (DC component) and analyses (DA component) of genomic datasets and in working cooperatively in large, distributed scientific projects?

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? 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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Are the plans to work with other Consortium members , including informatics components of individual research groups, the different components of the EDCAC, and the AWG, reasonable and appropriate? Are the milestones, timelines, and goals proposed for the research project reasonable and appropriate?

For applicants to the DC component:

• What is the likelihood that the proposed center can effectively track the progress of ENCODE activities?
• Are the plans to import, store, and disseminate the relevant ENCODE data reasonable and appropriate?
• Are the plans for the release of resources and data, including evidence that systems are in place to support data release, 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 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 training and providing support to users of the EDCAC with different levels of bioinformatics skills reasonable and appropriate?

For applicants to the DA component:

• Does the applicant propose a DA component that can transform data and facilitate analyses for genome-wide ENCODE data?
• What is the likelihood that the proposed project can effectively facilitate the integrative analysis of ENCODE data?
• Are the plans to disseminate the relevant ENCODE analyses reasonable and appropriate?
• Are the plans to identify and recruit groups with needed expertise for the analyses 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?

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

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/priority 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) Genome Wide Association Studies (GWAS).

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHGRI , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments 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/priority 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 and 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.

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. 

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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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-11-026 and for performing the scientific activities.
• Setting project milestones for the goals of the appropriate component of the EDCAC.
• Interacting with all of the participants of the ENCODE Research Consortium to determine data standards, file formats, and exchange mechanisms to coordinate data and metadata received from each ENCODE data production center.
• For the DC component, ensuring that the data submitted to the EDCAC are made publicly available rapidly and can be retrieved from the EDCAC through multiple methods of querying including simple web interfaces, web services, and tools to allow downloading of large datasets. 
• For the DA component, coordinating the activities of the Analysis Working Group (AWG) to promote the analyses of data from the ENCODE Project.
• Sharing results according to the data release policy developed for and by this project.
• Participating in group activities, including attending periodic workshops to discuss the Project's progress, contributing to analyses of ENCODE Research Consortium data, and coordinating the publication of research results.
• Serving as a member of the ENCODE Research Consortium Steering Committee.
• Fully disclosing algorithms, software source code, and experimental methods to the other members of the Consortium for the purpose of scientific evaluation.
• 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.
• Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and the External Consultants Panel.
• 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. However, the role of NIH staff will be to facilitate and not to direct the activities. 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.

The Project Scientist 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.
• Negotiate milestones 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 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.
• Report periodically on the progress of the ENCODE Project to the 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.

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, NHGRI about the progress and scientific direction of all components of the program. The External Consultants Panel will be composed of six 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 of NHGRI about changes, if any, that may be necessary in the ENCODE Research Consortium program.

Areas of Joint Responsibility include:

The Steering Committee will serve as the main coordinating board of the ENCODE Research Consortium established under this FOA. 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 membership will include one NIH Project Scientist and the P.I. from each awarded cooperative agreement. The Steering Committee may add additional members. Other government staff may attend the Steering Committee meetings if their expertise is required for specific discussions. 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 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

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 Non-Competing Continuation Grant Progress Report (PHS 2590) 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 theNIH 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.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email:

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Peter Good Ph.D.
Program Director, Genome Informatics
Division of Extramural Research
National Human Genome Research Institute (NHGRI)
5635 Fishers Lane, Ste. 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-496-7531
FAX: 301-480-2770
E-mail: goodp@mail.nih.gov

Ken Nakamura, Ph.D.
Scientific Review Officer
Scientific Review Branch
National Human Genome Research Institute (NHGRI)
5635 Fishers Lane, Ste. 4076, MSC 9305
Bethesda, MD 20892-9305 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-402-0838
FAX: 301-435-1580
E-mail: nakamurk@mail.nih.gov

Cheryl Chick
Grants Administration Branch
National Human Genome Research Institute (NHGRI)
5635 Fishers Lane, Suite 3058
Bethesda, MD 20892-9307
Phone: 301-435-7858
Fax: 301-451-5434
E-mail: chickc@mail.nih.gov

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 Parts 74 and 92.