Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
National Human Genome Research Institute (NHGRI) (http://www.genome.gov)

Title: A Data Analysis Center for the Encyclopedia of DNA Elements (ENCODE) Project (U01)

Announcement Type
New

Update: The following update relating to this announcement has been issued:


Request For Applications (RFA) Number: RFA-HG-07-010

Catalog of Federal Domestic Assistance Number(s)
93.172

Key Dates
Release Date:  July 18, 2007
Letters of Intent Receipt Date(s): August 6, 2007
Application Receipt Date(s): September 20, 2007
Peer Review Date(s): November 2007
Council Review Date(s): January  2008
Earliest Anticipated Start Date(s): April 1, 2008
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: September 21, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

Section II. Award Information
  1. Mechanism(s) of Support
  2. Funds Available

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
  2.Cost Sharing or Matching
  3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Address to Request Application Information
  2. Content and Form of Application Submission
  3. Submission Dates and Times
    A. Receipt and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
    A. Cooperative Agreement Terms and Conditions of Award
      1. Principal Investigator Rights and Responsibilities
      2. NIH Responsibilities
      3. Collaborative Responsibilities
      4. Arbitration Process
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The purpose of this RFA is to solicit applications for a Cooperative Agreement (U01) award to develop and implement a Data Analysis Center (DAC) as part of the Encyclopedia of DNA Elements (ENCODE) Project to support, facilitate and enhance integrative analyses of the data forthcoming from the project.  The goal of the ENCODE Project is to apply high-throughput, cost-effective approaches to generate a catalog of functional elements in the human genome. The ENCODE Project is currently in a pilot phase focused on the development of efficient large-scale approaches to identify all of the sequence-based functional elements in genomic DNA by focusing on a selected 30 Mb (1%) of the human genome (see www.genome.gov/ENCODE). RFA-HG-07-030, “Creating the Encyclopedia of DNA Elements (ENCODE) in the Human Genome”, was issued in November 2006 to continue the support of pilot projects and to support production centers that will expand the ENCODE Project to the interrogation of the entire human genome sequence. A companion RFA , RFA-HG-07-031, “A Data Coordination Center for the Encyclopedia of DNA Elements (ENCODE) Project”, was issued at the same time to solicit applications for a Data Coordination Center (DCC) to develop, house, and maintain databases to track, store, and provide access to the data generated as part of the ENCODE Project.  This next phase of the ENCODE Project will be funded in September 2007.  Projects funded through RFAs HG-07-030 and HG-07-031 and through the current RFA (HG-07-010) will participate in a Research Consortium that will be a continuation of the existing ENCODE Consortium.  For the current pilot project and the planned next phase of the ENCODE Project, the necessary integrative analyses are coordinated by the Analysis Working Group (AWG).  This RFA (HG-07-010) solicits applications for a DAC that will facilitate the activities of the AWG by providing resources necessary to accomplish integrative analyses of the Project data.  Working with the AWG, the DAC will coordinate the activities of the informatics groups of the individual Consortium member groups, the DCC, and the AWG; identify integrative analyses that should be carried out with the ENCODE data; perform all necessary data transformations and analyses with ENCODE data; and provide final ENCODE analysis data sets to the broad scientific community.

Background

The NHGRI initiated the Encyclopedia of DNA Elements (ENCODE) Project in 2003 to develop a comprehensive encyclopedia of all sequence-based functional elements, a resource that is needed to fully utilize the sequence of the human genome to better understand human biology, to understand the biology of disease, to predict potential disease risk, and to stimulate the development of new therapies and other interventions for preventing and treating disease.  The ENCODE Project started with two components. The first was a pilot in which available methods for the identification of functional sequence elements were tested and compared using a defined one percent (30 Mb) of human genomic DNA (for information about the selected target sequences, see http://www.genome.gov/10506161). The goals of the pilot phase were to test the ability of existing technologies to be applied at high-throughput in an efficient and cost-effective manner, to identify gaps in our ability to fully annotate the human genome and to set a clear path forward for scaling up these efforts to characterize the entire human genome in detail, efficiently and effectively.  The second component addressed the need for new or better technologies to identify both previously known and as-yet unknown sequence-based functional elements on a genome-wide scale. For a full list of the participants in the ENCODE pilot and technology development components, see http://www.genome.gov/12513391.

The ENCODE Project is unique among genome-scale projects to date in terms of both the number of different data types that have been generated and the challenges presented by the need to integrate the different data types to build successfully the encyclopedia of functional elements in the human DNA sequence.   For the pilot phase, the data analysis occurs at several levels, beginning with the analyses conducted by the individual laboratories on their own data.  Then, under the umbrella of an Analysis Working Group (AWG), these individual results had to be assembled, analyzed, and synthesized at the level of specific functional elements.  Finally, integration across different functional elements has constituted yet another level of analysis. The results of these analyses, which will be published within the next year, have not only revealed many interesting scientific discoveries, but have also enabled NHGRI to identify strengths and weaknesses in the current strategies for building the encyclopedia and to design improved approaches for the scale-up phase of the ENCODE Project to analyze the complete human genome. 

The outcomes of the pilot phase have led to the decision to continue the pursuit of the long-term goal of the ENCODE Project to identify comprehensively sequence-based functional elements in the entire human genome. To implement the next phase, two RFAs were issued in late 2006.  The first RFA dealt with data production, calling for (1) production-level efforts that scale to the entire human genome, using methods that have been clearly demonstrated to identify sequence-based functional elements efficiently, comprehensively, cost-effectively, and in a reasonable time frame and (2) additional pilot-level efforts. The second RFA solicited applications for a Data Coordination Center (DCC) to track, store, and disseminate primary data, processed data, and metadata from the ENCODE Project.

During the pilot phase, the integrative analyses necessary to examine the biological significance of ENCODE data proved to be a challenging activity.  The data were of multiple types with different platforms and analysis methods being employed. Integrative analyses were performed by an Analysis Working Group (AWG) and by sub-groups of the AWG; these sub-groups included not only people from ENCODE Project groups, but others with specialized expertise. These integrative analyses were effective in combining the several different types of ENCODE data to better identify different classes of functional elements.  For example, identification of RNA transcripts involved combining tiling microarray expression data, available public cDNA and EST data, and data from tag sequencing of the 5’ ends of cap-selected RNAs.  Similarly, identification of promoters required combining data on DNase hypersensitive sites, transcription factor binding regions, RNA polymerase binding regions, and histone modifications.  At the next level, constrained sequences, determined from comparative genomic data, were mapped to functional elements identified by experimental methods. These analyses were published recently (Nature 447, 799-816 <http://www.nature.com/nature/journal/v447/n7146/full/nature05874.html>.

However, the ability of the AWG to perform all necessary analyses would have been greatly facilitated by centralized coordination of their activities and by the availability of dedicated resources to support analyses.  For example, although different sub-groups of the AWG would perform similar analyses, because they used slightly different datasets, the results were difficult to compare between sub-groups.  Also, the AWG had to depend on members of the different research groups to perform certain standard analyses on a volunteer basis.  These deficiencies reduced the efficiency of integrative analysis of all data from the ENCODE Consortium during the pilot phase.  This RFA is designed to address these deficiencies for the next phase of ENCODE by providing an infrastructure to facilitate integrative analyses of the ENCODE datasets.

The next phase of the ENCODE Project will have three levels of informatics activities.  1)  Each research group will be responsible for the analysis of its own data to identify a specific type of functional sequence element.  This informatics pipeline is a requirement of the production centers solicited by RFA HG-07-030.  2)  The DCC, solicited by RFA HG-07-031, will be responsible for tracking, storing and disseminating ENCODE data from each group.  3) Finally, an AWG, with the support of the DAC solicited by this RFA, will be responsible for integrative analyses of data from each group along with other relevant data from the literature.  The AWG will be composed of members of the ENCODE Consortium and any additional researchers needed to provide a particular analysis expertise.  The AWG will be responsible for defining the integrative analyses to be performed to maximize the utility of these data.

Research Scope

This RFA (HG-07-010) is being issued to establish a Data Analysis Center (DAC) for the ENCODE Project to provide an informatics resource that will assist the AWG by coordinating and facilitating integrative analyses of the ENCODE data. The DAC will be a component of the AWG and will work with the informatics components of the individual ENCODE data production centers, the DCC, and the AWG. This DAC will provide resources and coordination activities that will enable the ENCODE Consortium to provide a final product at the end of the project that will be useful for the larger biomedical research community to locate functional sequence elements in the human genome.

As an overview, the DAC will be expected to: 

1) interact with ENCODE Consortium members, including the data producers, the DCC, and the AWG;

2)  collaborate with members of the AWG to establish a working environment for integrative analyses of ENCODE data;

3) work within the AWG to identify the types of analyses that need to be performed to generate an accurate catalog of functional elements; 

4)  organize data analysis workshops that will bring together the data producers and experts in data analysis for face-to-face interactions needed to promote better data analysis;

5)  plan and implement regular conference calls within the AWG to coordinate analyses;

6)  coordinate with the DCC to provide support, including data transformations and preparation of data freezes, for any data analyses agreed upon by the AWG;

7) perform analyses agreed upon by the AWG that compare different datasets using a variety of statistical methods to identify correlations between different data types;

8) facilitate interactions between the AWG and ENCODE Consortium members or outside investigators to supply comparative genomic datasets for use in integrative analyses;

9)  provide reports back to the ENCODE Consortium on the results from the integrative analyses;

10) interact with the DCC and other informatics resources to disseminate results from the AWG;

11) work with the AWG in the preparation of manuscripts for publication by the ENCODE Consortium; and

12) provide a vehicle for interactions related to data analysis with the members of the model organism ENCODE (modENCODE) Consortium, a related project with a goal of identifying functional sequence elements in the genomes of C. elegans and D. melanogaster (http://www.modencode.org).

The applicant should describe a broad plan for how the DAC will accomplish the goal of facilitating the work of the AWG, including a description of how the specific activities listed above will be accomplished.  The plan also should describe how the DAC will interact with the AWG and the rest of the ENCODE Consortium.  If necessary, the DAC, after discussions with the AWG, should be prepared to assist 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 to participate in the integrative analyses of the ENCODE data; if such funds are requested, the applicant should describe the process by which they will be dispersed. 

The DAC will obtain data from, and provide feedback to, the DCC about the quality and utility of the data in the DCC.  The DAC should be prepared to work with data and metadata from the range of different experimental and computational projects that are expected to comprise the ENCODE production phase.  The specific data types will be determined only at the time the awards are actually made, in September 2007.  However, the current ENCODE pilot project provides examples of the types of data expected to be analyzed, such as data from comparative sequencing, promoter reporter assays, microarray chip hybridization assays from a variety of different experimental approaches, and assays to identify DNase hypersensitive sites.  (The project descriptions at http://www.genome.gov/12513391 provide a complete listing of experimental approaches in the current ENCODE pilot project.)  In addition, plans for the DAC should be flexible enough to accommodate the analyses of new data types that might be available in future.  The DAC will be expected to facilitate the integrative analysis of data at both the pilot and genome-wide levels that will be funded by the RFA. 

The applicant must have demonstrated prior experience in successfully leading the coordinated analyses of genomic data sets such as those anticipated to be generated by the ENCODE Project. The exact boundaries of the activities of the AWG, DAC, DCC, and the members of the ENCODE Consortium are not possible to predict at this time, and will depend in large degree on the capacities and experience of the projects that participate in the ENCODE Consortium.  Applicants should describe their willingness to be flexible in assuming or relinquishing responsibilities as program needs arise.   Since the DAC will have to work closely with the AWG, the applicant also must have demonstrated ability to work cooperatively within large, distributed scientific projects.  

The activities of the DAC should not overlap with either the local informatics activities of each production center or the activities of the DCC, but should complement each of these informatics components. As a reminder, the ENCODE DCC will be funded to develop, house, and maintain databases to track, store, and provide access to all of the different types of data and metadata generated as part of the ENCODE Project.  In addition, the DCC will import data from related projects that are relevant to the goals of the ENCODE Project.  While the specific objectives of, and the types of data that will be produced by, the production efforts and collected by the DCC have not yet been defined, the applicant for the DAC should make clear his/her intention to avoid duplication of efforts with these other components of ENCODE.

In addition to a clear set of goals for the overall DAC project, the applicant should propose milestones with metrics that will allow assessment of progress towards the achievement of the ultimate goals.  For example, these goals could include any planned software development activities, any planned analysis workshops, the anticipated level of throughput for capturing and processing data from the DCC, and the anticipated number of analyses that can be coordinated during the project period. Milestones may be negotiated at the time of the award and updated on a yearly basis as described in the terms and conditions of a Cooperative Agreement in section 2.A.2. 

The DAC is expected to be a stable resource that will facilitate the analysis activities of the ENCODE Consortium and its component members. The DAC should use robust, existing software tools capable of handling all of the ENCODE data that will be used in integrative analyses. Where possible, the applicant should use existing software modules for the DAC. The DAC is expected to be able to work with the other funded projects of the ENCODE Consortium to establish the exact types and formats of data that will be used in integrative analyses along with developing procedures to track and facilitate the analyses.

The ENCODE Project will be run as a Research Consortium that will be open to all academic, government, and private sector scientists interested in participating in an open process to facilitate the comprehensive annotation of the human genome. The awardee funded through this RFA (HG-07-010) will participate in this Research Consortium.  The applicant should request funds to attend Research Consortium meetings that will be held at least once a year.

The ENCODE Project has been designated a “community resource project’, as defined by a meeting on data release held in Ft. Lauderdale, Florida in January 2003. (http://www.genome.gov/Pages/Research/WellcomeReport0303.pdf).  The DAC will be expected to make the ENCODE data and resultant analyses freely available to the scientific community in a timely manner.  Timeliness is particularly important because NHGRI anticipates that there will be considerable interest on the part of non-Consortium members in analyzing the data as well.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the U01 Cooperative Agreement award mechanism(s).

The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".  This RFA is a one-time solicitation.  At the current time, NHGRI anticipates that this will be a four-year project unless circumstances warrant a continuation of this effort.

2. Funds Available

The NHGRI intends to comment approximately $1 million dollars in FY 2008 to fund 1 new cooperative agreement in response to this RFA.  An applicant may request a project period of up to 4 years.  The earliest anticipated award date is March 1, 2008.

Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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.

More than one PI, or multiple PIs, may be designated on the application. Additional information on the implementation plans and policies and procedures to formally allow more than one PI on individual research awards can be found at http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

No cost sharing or matching is required for applications submitted in response to this RFA.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided they are scientifically distinct.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date(s): August 6, 2007
Application Receipt Date(s): September 6, 2007
Peer Review Date(s): November-December 2007
Council Review Date(s): January2008
Earliest Anticipated Start Date(s): April 1, 2008

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Peter Good, PhD
Program Director, Genome Informatics
Division of Extramural Research
National Human Genome Research Institute
5635 Fishers Lane, Suite 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
Email: goodp@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 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)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

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

Rudy Pozzatti, PhD
Scientific Review Administrator
Scientific Review Branch
National Human Genome Research Institute
5635 Fishers Lane, Ste. 4076, MSC 9306
Bethesda, MD 20892-9306 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 402-0838
Email: pozzattr@exchange.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NHGRI. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.


6. Other Submission Requirements

The Research Plan (sections A-D) should not exceed 25 pages.

Appendix material should conform to new limits on appendix materials as described in the NIH Guide Notice NOT-OD-07-018 <http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html>.

Plan for Sharing Research Data

The NHGRI is committed to the principle of rapid data release to the scientific community.  This principle was initially implemented during the Human Genome Project and has been recognized as leading to one of the most effective ways of promoting the use of the genome sequence data to advance scientific knowledge. At a meeting in Ft. Lauderdale, FL that was co-sponsored by the Wellcome Trust and NHGRI in January 2003, the concept of rapid data release by genomic sequence data producers was reaffirmed, and the attendees strongly recommended applying the practice to other types of data produced by “community resource projects”. The attendees recognized, however, that different issues, particularly with respect to data validation, would be involved in the development of appropriate release practices for different types of data. Since they also recognized that sustaining the practice of rapid, prepublication data release by community resources requires that the interests of all involved - including the data producers, data users, and funding agencies - be addressed, they emphasized the need to develop a tripartite system of responsibility. The meeting report from the Ft. Lauderdale meeting can be found on the Wellcome Trust website at http://www.wellcome.ac.uk/doc_wtd003208.html.

The NHGRI has identified the ENCODE Project as a community resource project. As such, the ENCODE Project aims to function openly by making all data available to the scientific community in a timely manner prior to publication. During the pilot phase, the ENCODE Consortium established a common Data Release Policy (see http://www.genome.gov/12513440) and all participants agreed to abide by that policy. It is expected that the general principles of this policy will continue during the next phase of the ENCODE Project. Additional specifications may be added, e.g., relating to timing of release of validated data. All applicants should provide specific plans for data release in the application and indicate their willingness to abide by the ENCODE Consortium Data Release Policy and any changes that may be made during the next funding period by the Consortium. The reasonableness of the data sharing plan will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.  

After completion of the initial review, NHGRI program staff will be responsible for any additional administrative review of the plan for sharing data. The adequacy of the data sharing plan will be considered by program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data sharing plan with the prospective awardee before recommending funding of an application. The final negotiated version of the data sharing plan will become a condition of the award of the cooperative agreement. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590).  See Section VI.3. Reporting.

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

As the ENCODE Project is a community resource project, NHGRI expects that not only data, but also resources generated during the course of the program should be made rapidly available to the research community and that sharing plans should follow the same principles and spirit as the rapid data release policy. The applicant should provide specific plans for resource sharing and distribution in the application. The reasonableness of the resource sharing plan will be assessed by the reviewers. However, reviewers will not factor the proposed resource sharing plan into the determination of scientific merit or the priority score. The adequacy of the resources sharing plan will be considered by the funding organization when making recommendations about funding applications. The presence of a resources sharing plan will be part of the terms and conditions of the award. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding 2590/2590.htm).

Section V. Application Review Information


1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the application address the goals and objectives outlined in the RFA?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the plans to work with other Consortium members, including the informatics components of individual research groups, the DCC, and the AWG, reasonable and appropriate? Does the applicant propose a DAC that can transform data and facilitate analyses for ENCODE data from both the ENCODE target regions and the entire human genome? What is the likelihood that the proposed center 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?  Are the plans for working with comparative genomic datasets reasonable and appropriate? Are the milestones, timelines, and goals proposed for the research project reasonable and appropriate?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Does the project efficiently use the available tools to accomplish the goals of the DAC? 

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Are the track records of the Principal Investigator and other key personnel in directing informatics activities related to a DAC reasonable and appropriate?  Does the Principal Investigator have demonstrated experience in coordinating analyses of genomic datasets and in working cooperatively in large, distributed scientific projects? 

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. Reviewers will be asked to consider the data sharing plan in the context of the ENCODE Consortium Data Release Policy, as described in section IV.6

2.D. Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 NIH U01 Cooperative Agreement award mechanism, 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 ENCODE Research Consortium will involve three distinct activities, the ENCODE data production centers, the ENCODE DCC, and the ENCODE DAC, solicited in RFAs HG-07-030, HG-07-031, and this RFA, respectively.  All components of the ENCODE Consortium awarded as a result of these RFAs will be funded by cooperative agreements and a single Steering Committee (see below) and a single External Consultants Panel (see below) will serve all of the ENCODE activities.  The Terms and Conditions described below are specific for this RFA (HG-07-010), but have been coordinated and made consistent with those described in the other RFAs soliciting components of the ENCODE Research Consortium.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for defining the details for the project within the guidelines of RFA HG-07-010 and for performing the scientific activities.  The P.I. will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Responsibilities".

The P.I. of the Data Analysis Center (DAC) for the ENCODE Project will:

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 HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

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 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:

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.

Additionally, an NHGRI 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 NIH Project Scientist.

2.A.3. Collaborative Responsibilities

The Steering Committee will serve as the main governing board of the ENCODE Research Consortium.  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 from RFAs HG-07-030, HG-07-031, and HG-07-010. 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 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 ENCODE Project; 2) address data management issues; 3) analyze ENCODE 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.

2.A.4. Arbitration Process

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 arbitration. An Arbitration 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit periodic (at least every three months) progress reports in a standard format, as agreed upon by the Steering Committee and External Consultants Panel.

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Peter Good, PhD
Program Director
Division of Extramural Research
National Human Genome Research Institute
5635 Fishers Lane, Ste. 4076, MSC 9305
Rockville, MD 20852 (courier/overnight service)
Bethesda, MD 20892-9305 (regular mail)
Telephone: (301) 496-7531
Email: goodp@mail.nih.gov

2. Peer Review Contacts:

Rudy Pozzatti, PhD
Scientific Review Administrator
Scientific Review Branch
National Human Genome Research Institute
5635 Fishers Lane, Ste. 4076, MSC 9306
Bethesda, MD 20892-9306 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 402-0838
Email: pozzattr@exchange.nih.gov

3. Financial or Grants Management Contacts:

Cheryl Chick
Grants Management Officer
Division of Extramural Research
National Human Genome Research Institute
5635 Fishers Lane, Ste. 4076, MSC 9306
Bethesda, MD 20892-9306 (U.S Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-7858
Email: ChickC@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


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