DETERMINATION OF ALL FUNCTIONAL ELEMENTS IN HUMAN DNA
RELEASE DATE: February 21, 2003
RFA: HG-03-003
National Human Genome Research Institute (NHGRI)
(http://www.genome.gov/)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.172
LETTER OF INTENT RECEIPT DATE: April 13, 2003
APPLICATION RECEIPT DATE: May 13, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE
The purpose of this RFA is to solicit applications to participate in a
Research Network that will conduct a pilot project to test and compare
methods for identifying all of the functional elements in a limited
(~1%) region of the human genome. The emphasis during this initial
phase will be on the identification and verification of transcription
units, including associated cis-regulatory elements, but projects using
existing methods for the identification of other sequence-based
functional elements are also encouraged. Both computational and
experimental approaches will be critical components of the project.
This RFA is being issued in conjunction with a second RFA, HG-03-004
"Technologies to Find Functional Elements in Genomic DNA" which will
support the development of new and improved high-throughput and
efficient technologies for the comprehensive identification and
verification of a larger variety of functional elements.
RESEARCH OBJECTIVES
Background
In April 2003, the sequence of the human genome will be essentially
complete. For the scientific community now to make the best use of
that fundamental information resource, the identity and precise
location of all sequence-based functional elements in the genome must
be determined. While many of the protein-coding genes are already
known, many others remain to be identified. Beyond open reading
frames, non-protein-coding genes, transcriptional regulatory elements
and determinants of chromosome structure and function remain largely
unknown. A comprehensive encyclopedia of all of these features is
needed to utilize fully the sequence of the human genome to understand
human biology better, to predict potential disease risks, and to
stimulate the development of new therapies and other interventions to
prevent and treat disease.
One of the primary reasons for the success of the Human Genome Project
has been the development and use of high-throughput strategies for data
generation, and the placement of the data immediately in the public
domain. Most of the sequence data, the underlying maps and the
sequence assemblies were generated through the use of large-scale
automated processes. Now, methods such as sequence analysis of whole
genomes, DNA microarray technology and mass spectrometry have been or
are being developed as high-throughput approaches for additional types
of genomic analyses, such as determining the parameters of gene
expression or the location of gene products by the thousands at a time
instead of individually. High-throughput methods to determine the
location of cis-regulatory elements and, to a lesser extent, other
sequence elements, are also beginning to be developed. However, at
present, there is no single approach or compilation of approaches known
to identify accurately and efficiently every sequence feature in
genomic DNA.
While determining the identity and function of all of the sequence
elements in human DNA is a daunting challenge, it is appropriate at
this time to begin to consider such a project. On July 23-24, 2002,
the NHGRI held a workshop, the Comprehensive Extraction of Biological
Information from Genomic Sequence, to discuss a proposal to initiate a
new public research consortium to test and compare existing and new
methods for exhaustive identification and verification of functional
sequence elements as a pilot project focused on a limited region of
human genomic DNA. The report of this meeting is available at
http://www.genome.gov/page.cfm?pageID=10005115.
Based on the recommendations of this workshop, the NHGRI has decided to
launch the Encyclopedia of DNA Elements (ENCODE) project. The goal of
this project is to comprehensively identify functional elements in the
human genome sequence. The ENCODE project will begin as a pilot
project that will test and compare methods for the exhaustive
identification and verification of functional sequence elements in 30
Mb of human genomic DNA. This will require access to information,
resources, ideas, expertise, and technology beyond the scope of what
any single group can currently provide. Therefore, the pilot will be
carried out by a consortium of investigators with diverse backgrounds
and expertise working cooperatively to (1) evaluate rigorously the
relative merits of each of a varied set of techniques, technologies,
and strategies for identifying all of the functional elements in human
genomic sequence, (2) test the abilities of such methods to be scaled
up efficiently so that ultimately, it will be feasible to use them to
analyze all of the functional elements encoded in the entire human
genome sequence, and (3) identify and fill gaps in our ability to
annotate genomic sequence.
The ENCODE project is intended to characterize the tools needed for
mining genomic sequence and, where necessary, improve them, and define
a clear path for the determination of all of the functional elements in
the entire human genome sequence. A fully annotated human genome
sequence will be an integrated information resource that will enable
the efforts of the entire research community in both basic and clinical
research.
It is obvious, however, that current technology is not capable of
achieving all of the aims of even the initial phase of the ENCODE
project. Therefore, at the same time that high-throughput efforts are
being initiated using well-developed technologies, a parallel effort is
being started to develop new or improved high-throughput and efficient
technologies. The companion RFA, HG-03-004, "Technologies To Find
Functional Elements in Genomic DNA", is intended to expand the
repertoire of tools that can be applied to the ENCODE, or similar
projects, in the future.
Research Scope
The aim of the ENCODE pilot project is to determine the best way to
generate a comprehensive catalog of all sequence-based functional
elements in human DNA. The pilot will test and compare a combination
of available methods, seek to improve current methods, and develop new
methods using, as a test bed, a defined 30 Mb of human genome sequence.
Both computational and experimental approaches will be involved. A
prime criterion by which any method or combination of methods will be
evaluated will be its potential for being efficiently applied at large
enough scale to characterize the entire human genome.
The sequence-based functional elements that will be targeted include,
but are not limited to:
o Transcribed sequences, including both protein-coding and non-
protein-coding. A description of the gene structure with
transcriptional start sites, polyadenylation sites, along with all
alternative transcripts, is an example.
o Conserved non-coding sequences that may represent functional
elements.
o Cis-acting elements that regulate transcription and/or chromatin
structure. These elements include promoters, enhancers, and
insulators.
o Sequence features that affect/control chromosome biology. Examples
include origins of replication and hot spots for recombination.
o Epigenetic changes, such as DNA methylation and chromatin
modifications.
If the ENCODE project is to be successful, it will be critical to
balance the desire for complete information about genome features with
the practical ability to obtain a useful amount of information in a
reasonable and affordable manner. Therefore, the scope for this RFA
will be limited to the initial identification and verification of
sequence-based elements. This limitation has a number of consequences:
o Although a minimum amount of functional analysis may be required in
the process of identification, in-depth study of the biological
function of genes and gene products, e.g., functional studies in
vitro or in vivo, is beyond the scope of this RFA.
o NHGRI recognizes that the function and activity of sequence elements
will vary in different cell types. As this RFA is being issued in
support of the ENCODE project's pilot phase, proposals should only
include as many different cells types as necessary to demonstrate
feasibility of the approaches proposed in the application. The
NHGRI will not specify cells or tissues to be used for this project;
however, proposals must clearly define the cells or tissues to be
studied along with a justification for their use.
o The goal of the pilot project is to test methods for identifying
functional elements in the human genome. Experimental work should
be restricted to human tissues and cells unless a compelling
argument can be made for the use of model organisms. The functional
analysis of sequences from other species that are homologous to the
selected target regions is beyond the scope of this solicitation.
The ENCODE consortium will be open to all academic, government and
private sector scientists interested in participating in an open
process to facilitate the comprehensive interpretation of the human
genome sequence. It is expected that groups with funding from other
sources will participate in the ENCODE project and therefore, funding
through this initiative is not a prerequisite for participation in the
consortium.
Participants will be expected to design experiments that apply high
throughput methods to identify, with high accuracy, functional elements
in the selected target sequences in the human genome. In the
application, the P.I. should describe the functional element to be
identified, the specific assay(s) to be used, the plans for scaling the
assay(s) for high-throughput analyses, and the collection and
processing of data from the experiments. In addition, applicants
should describe how the biological authenticity of the identified
elements could be validated, and plans to validate the technical
approach should be included. The large datasets from these experiments
will be deposited in the ENCODE database(s), and other appropriate
public databases, as described in the data release policy (see below).
Through interactions within the ENCODE consortium, the P.I.s may modify
their experimental approach, either incorporating modified or new
methods or using new information supplied to the ENCODE consortium,
such as improved computer predictions of functional elements.
To help plan certain initial aspects of the ENCODE pilot project, NHGRI
convened an Organizing Committee which identified a set of target
regions of the genome for study (see below) and recommended a proposed
set of data release policies. Once the project has been initiated, it
will be organized as a Research Network with a Coordinating Committee
(see Terms and Conditions), which will guide the operations of the
consortium. A Scientific Advisory Panel, comprised of scientists not
directly working on the project, will be convened to provide advice to
the Director, NHGRI regarding the progress of the project.
Target Regions. The 30 Mb target regions to be analyzed in the ENCODE
pilot project include representative features of the entire genomic
landscape. There are forty-four regions altogether, ranging in size
from 500 Kb to 2 Mb. Approximately 50% of the 30Mb of sequence was
chosen manually, based upon two criteria: 1) the existence of an
extensive amount of comparative sequence data for a region, and 2)
interesting gene(s) or other sequence features residing in a region.
The remaining 15Mb were selected randomly using a computer algorithm
that stratified the human genome based upon two criteria – gene density
and non-exonic conservation with mouse sequence – and then selected
regions representative of each stratum. The list of target regions, as
well as a more detailed description of the selection process, can be
found at http://www.genome.gov/page.cfm?pageID=10005107. Applicants
must propose to study the entire set of target regions rather than
focus on only one or a subset of regions.
Comparative sequence analysis of regions homologous to the selected
target regions will undoubtedly provide valuable information for
discerning functional sequence elements and it is anticipated that
these sequences will be determined for a number of species during the
course of the ENCODE pilot project. The de novo generation of
additional sequence information by standard methods will not be
supported under this RFA, but comparative sequences will be made
available through the consortium's database.
Data Release. The ENCODE project aims to function openly by making all
data available to the scientific community in a timely manner. The
ENCODE project is a community resource project. It is expected that the
consortium will establish a common data release policy and that all
participants will agree to abide by that policy. The Organizing
Committee has recommended to NHGRI a set of practices for data release.
Taken together with other considerations, the NHGRI deems that the
following data release policy would be appropriate:
1. Participants would submit data to the consortium database(s) as soon
as the data have been determined to be reliable. The timing of data
submission may differ for different types of data. The consortium's
Coordinating Committee in conjunction with the Scientific Advisory
Panel would establish appropriate data release standards for each
data type. Approval for participation in the consortium will be
predicated on agreement to abide by these data release standards.
Applicants should propose what they consider to be appropriate data
release practices in the application, and a policy acceptable to the
investigator, the consortium and NHGRI will be negotiated at the
time of award.
2. Consortium participants would submit data to the consortium
databases in the specified format.
3. Upon submission, all data would be made freely available to the
entire research community in a form that would allow for redisplay
and reanalysis, so that maximal utility of this community resource
could be achieved. It is NHGRI's expectation that users of these
data would respect the legitimate interests of the producers to
analyze and publish their results by treating the data as
unpublished information, until otherwise indicated. As with any
unpublished data, it would be expected that users would provide
proper citation of the source of the data. The best interests of
all are served when all act responsibly to promote the highest
standards of respect for scientific work. In some cases, this might
best be done by discussion or coordination with the resource
producers.
4. The individual investigators within the consortium may publish the
results of their own work that have been submitted to the ENCODE
project's database(s) in the course of that work. Neither these
individual publications nor any consortium publications should hold
up the other's publications.
5. The consortium intends to publish global analyses of the results of
the pilot project. At the same time, the consortium recognizes that
it has the responsibility to do so in a timely manner. While it is
not possible, at present, to predict an appropriate time for any
such publication(s), the consortium, with guidance from the
Scientific Advisory Panel, will establish a timeframe once the
project has been launched and there is a better understanding of the
timeframe and scope of the project.
6. Publicly funded consortium participants would fully disclose
algorithms, software source code, and experimental methods to the
other members of the consortium for purposes of scientific
evaluation and will be strongly encouraged to make them available to
the broad research community.
Applicants should address data release in their applications either by
agreeing to abide by the proposed ENCODE data release policy stated
above or by proposing alternative approaches to make the ENCODE data
available for the consortium to consider. Ultimately, the ENCODE
consortium will develop a common data release policy for all
participants. Funding of any award under this RFA will be contingent on
negotiation of a data release policy that is acceptable to the
applicant, to the consortium and to the NHGRI.
Resources for the ENCODE project. To facilitate the project, the
storage, display and release of data generated by the consortium will
be coordinated through a central database. Ultimately, this database
will become a knowledgebase that will be a central repository for
information about the selected genome regions. This database will not
be supported by this RFA.
During the course of the ENCODE pilot project, it may be necessary or
efficient for the NHGRI to provide common sets of reagents and
resources in support of the consortium's research activities. It is
not possible, however, to anticipate what resources may be needed prior
to the establishment of the consortium and the funding of specific
projects. Therefore, each applicant should propose to develop or
procure the resources needed for the research project and request the
necessary funds to do so. The costs for these resources should be
clearly described in the budget justification section of the
application. If common reagents and resources are developed through
the course of the project, NHGRI will negotiate any appropriate changes
to the award's budget. All common reagents developed for the
consortium, including clones, microarrays, and software, would be made
available to the entire scientific community.
Training. The applicant is strongly encouraged to propose a plan in
response to NHGRI's Action Plan for increasing the number of
underrepresented minorities in genome research. Please see
http://www.genome.gov/page.cfm?pageID=10003996 for a description of the
Action Plan.
In summary, applicants for awards under this RFA:
1. should provide plans to study the entire set of target regions;
2. should provide a detailed cost breakout for the development or
procurement of specialized resources;
3. should provide specific plans for data release;
4. are strongly encouraged to provide a plan for training
underrepresented minorities.
MECHANISM OF SUPPORT
This RFA will use the NIH U01 Research Project Cooperative Agreement,
the U19 Research Program Cooperative Agreement, and the U41
Biotechnology Resource Cooperative Agreement award mechanisms in which
the Principal Investigators retain the primary responsibility and
dominant role for planning, directing, and executing their components
of the ENCODE pilot project, with NIH staff being substantially
involved as a partner with the Principal Investigators, as described
under the section "Cooperative Agreement Terms and Conditions of
Award". This RFA is a one-time solicitation, and uses just-in-time
concepts. The earliest anticipated award date is September 30, 2003.
Applications that are not funded in the competition described in this
RFA may be resubmitted as NEW investigator-initiated applications using
the standard receipt dates for NEW applications described in the
instructions to the PHS 398 application.
FUNDS AVAILABLE
The NIH intends to commit approximately $10 million total costs in FY
2003 to fund five to fifteen awards in response to this RFA. An
applicant may request a project period of up to three years. Awards
pursuant to this RFA are contingent upon the availability of funds and
the receipt of a sufficient number of meritorious applications. At
this time, it is not known if this RFA will be reissued.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
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 programs.
SPECIAL REQUIREMENTS FOR COOPERATIVE AGREEMENTS
Cooperative Agreement Terms and Conditions of Award
The following terms and conditions will be incorporated into the award
statement of each cooperative agreement awarded under RFA HG-03-003 and
will be provided to the Principal Investigators and the appropriate
institutional officials at the time of award. The following special
terms of award are in addition to, and not in lieu of, otherwise
applicable OMB administrative guidelines, DHHS grant administration
regulations at 45 CFR Parts 74 and 92, as are other DHHS, NIH, and
(NHGRI) grant administration policies:
1. Cooperative Agreement
The administrative and funding instruments used for this program will
be the NIH U01 Research Project Cooperative Agreement, the U19 Research
Program Cooperative Agreement, or the U41 Biotechnology Resource
Cooperative Agreement award mechanisms. The cooperative agreement is
an "assistance" mechanism (rather than an "acquisition" mechanism), in
which substantial NIH scientific and programmatic involvement with the
awardee is anticipated during the performance of the activity. Under
the Cooperative Agreement, the NIH purpose is to support and stimulate
the recipient's activity by involvement in and otherwise working
jointly with the award recipient in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the
activity. Consistent with this concept, the dominant role and prime
responsibility for the project as a whole will reside with the
awardees, although specific tasks and activities in carrying out the
study will be shared among the awardees and the NIH Program Director.
2. P.I. Rights and Responsibilities
The P.I. will have the primary responsibility for defining the details
for the project within the guidelines of RFA HG-03-003 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 Program Staff Responsibilities".
The P.I. of an ENCODE pilot project component will:
o Determine experimental approaches, design protocols, set project
milestones, and conduct experiments.
o Analyze the entire set of selected regions and not just a subset of
the target sequences; OR, lead a research group composed of several
individuals with a shared experimental approach with each individual
examining a part of the target sequences, provided that the group as
a whole will gather data on the entire set of target regions and
that the P.I. will take responsibility for this.
o Share results according to the data sharing policy developed for and
by this project.
o Participate in group activities, including attending periodic
workshops to discuss the project's progress and coordinating the
publication of research results.
o Fully disclose all algorithms, software source code, and
experimental methods to the other members of the consortium for
purposes of scientific evaluation.
o Not disclose confidential information obtained from other members of
the consortium.
o Adhere to NHGRI policies regarding intellectual property and other
policies that might be established during the course of this
activity.
o Submit periodic progress reports in a standard format, as agreed
upon by the Coordinating Committee and Scientific Advisory Panel.
o Accept and implement the common guidelines and procedures approved
by the Coordinating Committee, Scientific Advisory Panel and NHGRI.
3. NIH Program Staff Responsibilities
The NIH Program Director is a scientist of the NHGRI extramural staff
who will provide normal stewardship of the award and, in addition, will
have substantial scientific and programmatic involvement during the
conduct of this activity through technical assistance, advice, and
coordination. 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 Network
Coordinating Committee and that NIH staff will be given the opportunity
to offer input to this process. One NHGRI Program Director will
participate as a member of the Coordinating Committee and will have one
vote. The Program Director will have the following substantial
involvement:
o Participate with the other Coordinating Committee members in the
group process of setting research priorities, deciding optimal
research approaches and protocol designs, and contributing to the
adjustment of research protocols or approaches as warranted. The
Program Director will assist and facilitate the group process and
not direct it.
o 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.
The Program Director will also coordinate the efforts of the
Research Network with groups participating in the ENCODE consortium.
o Attend all Coordinating 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 Program Director
must be informed of all major interactions of members of the
Coordinating Committee. The NIH Program Director will be
responsible for scheduling the time and preparing concise minutes or
summaries of the Coordinating Committee meetings, which will be
delivered to members of the group within 30 days after each meeting.
o Report periodically on the progress of the ENCODE pilot project to
the Director, NHGRI.
o 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 Scientific Advisory
Panel.
o Serve as a liaison between the Coordinating Committee and the
Scientific Advisory Panel, attending Scientific Advisory Panel
meetings in a non-voting liaison member role.
o Serve on subcommittees of the Coordinating Committee and the
Scientific Advisory Panel, as appropriate.
o Assist awardees in the development, if needed, of policies for
dealing with situations that require coordinated action.
o Provide advice in the management and technical performance of the
investigation.
o Assist in promoting the availability of the ENCODE and related
resources developed in the course of this project to the scientific
community at large.
o Participate in data analyses, interpretations, and, where warranted,
co-authorship of the publication of results of studies conducted
through the ENCODE Research Network.
4. Collaborative Responsibilities
The Coordinating Committee will serve as the main governing board of
the ENCODE Research Network established under this RFA. It is
anticipated that additional coordination mechanisms will be set up with
other U.S. and international groups that may join this effort. The
Coordinating Committee membership will include one NIH Program Director
and the P.I. from each awarded cooperative agreement. The Coordinating
Committee may add additional members. Other government staff may
attend the Coordinating Committee meetings, if their expertise is
required for specific discussions.
The Coordinating Committee will be responsible for coordinating the
activities being conducted by the ENCODE Research Network. To address
particular issues, the Coordinating Committee may establish working
groups as needed, which will include representatives from the Research
Network and the NHGRI and possibly other experts. Such groups might
include ones to: 1) develop a list of common reagents needed for the
pilot project; 2) address data management issues; 3) analyze the pilot
project data; 4) develop quality standards and methods to assess data
quality; and 5) handle communication issues and develop principles for
reporting findings.
5. Scientific Advisory Panel
A Scientific Advisory Panel will be established by the NHGRI to
evaluate the progress of the ENCODE Research Network. The Scientific
Advisory Panel will provide recommendations to the Director, NHGRI
about the progress and scientific direction of all components of the
program. The Scientific Advisory 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 Scientific Advisory 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 Coordinating Committee to
allow the members of the both the Scientific Advisory Panel and the
Coordinating Committees to interact directly with each other. Twice a
year the Scientific Advisory Panel will make recommendations regarding
progress of the ENCODE Research Network and present advice to the
Director of NHGRI about changes, if any, that may be necessary in the
ENCODE Research Network program.
6. Arbitration Process
Any disagreement that may arise on scientific or programmatic matters
within the scope of the awards between award recipients and the NIH may
be brought to arbitration. An Arbitration Panel will be convened,
which will be composed of three members: (1) a designee of the
awardee, (2) an NIH designee, and (3) a third designee with relevant
expertise who is chosen by the other two. The Arbitration Panel will
help resolve scientific or programmatic issues that develop during the
course of work that restrict progress. This special arbitration
procedure in no way affects the awardee's right to appeal an adverse
action that is otherwise appealable in accordance with NIH regulations
42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA 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:
o Direct your questions about scientific/research issues to:
Elise Feingold, PhD or Peter Good, PhD
Program Directors
Division of Extramural Research
NHGRI
Building 31, Room B2B07
Bethesda, MD 20892-2033
Telephone: (301) 496-7531
FAX: (301) 480-2770
Email: Elise_Feingold@nih.gov or GoodP@mail.nih.gov
o Direct your questions about peer review issues to:
Rudy Pozzatti, PhD
Scientific Review Administrator
Division of Extramural Research
NHGRI
Building 31, Room B2B37
Bethesda, MD 20892-2032
Telephone: (301) 402-0838
FAX: (301) 435-1580
Email: pozzattr@mail.nih.gov
o Direct your questions about financial or grants management matters
to:
Jean Cahill
Chief, Grants Administration Branch
Division of Extramural Research
NHGRI
Building 31, Room B2B34
Bethesda, MD 20892-2031
Telephone: (301)435-7858
FAX: (301) 402-1951
Email: cahillj@mail.nih.gov
7. Prospective applicant meeting. There will be a combined meeting at
the Natcher Conference Center on the NIH campus from 9:00 a.m. to
approximately 2:00 p.m. on March 7, 2003 to launch the ENCODE project
and to answer questions about the RFA from prospective applicants.
Attendance at this meeting is not a prerequisite for responding to the
RFA or for participation in the ENCODE consortium. For more
information about this meeting, see
http://www.genome.gov/Pages/Research/ENCODE/ or email: encode@mail.nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
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:
Elise Feingold, PhD
Program Director, Genome Analysis Program
Division of Extramural Research
NHGRI
Building 31, Room B2B07
Bethesda, MD 20892-2033
Telephone: (301) 496-7531
FAX: (301) 480-2770
Email: Elise_Feingold@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). The PHS 398 is
available at https://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form 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:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: 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
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application
must be sent to:
Rudy Pozzatti, PhD
Scientific Review Administrator
Division of Extramural Research
NHGRI
Building 31, Room B2B37
Bethesda, MD 20892-2032
Telephone: (301) 402-0838
FAX: (301) 435-1580
Email: pozzattr@mail.nih.gov
APPLICATION PROCESSING: Applications must be received on or before the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and
funding assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA 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 an RFA, it is to be prepared as a NEW
application. That is the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text
must not be marked to indicate the changes. While the investigator may
still benefit from the previous review, the RFA application is not to
state explicitly how.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NHGRI.
Incomplete applications will be returned to the applicant without
further consideration.
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 the NHGRI in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will:
o Receive a written critique
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a second level review by the National Advisory Council for
Human Genome Research.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments, reviewers will be asked to discuss the
following aspects of your application in order to judge the likelihood
that the proposed research will have a substantial impact on the
pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these
criteria in assigning your application's overall score, weighting them
as appropriate for each application. Your 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,
you may propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.
The application must be directed toward attaining the programmatic
goals as stated under RESEARCH OBJECTIVES. The following criteria will
be used by peer review groups to evaluate these applications:
(1) SIGNIFICANCE: Does the application address the problem outlined in
this RFA?
(2) APPROACH: Are the conceptual framework, design, methods, and
analyses adequately developed, well integrated, and appropriate to the
aims of the project as outlined in this RFA? Are potential problem
areas acknowledged and alternative tactics considered? Does the
applicant propose to study the entire set of target regions? Does the
technical approach have the potential to be applied efficiently and
cost-effectively at large scale? Will the experiments proposed
demonstrate that potential?
(3) INNOVATION: Does the project employ novel concepts, approaches, or
methods for identifying and verifying sequenced-based functional
elements? Does the project develop new methods or technologies to
reduce costs or increase quality or throughput?
(4) INVESTIGATOR: Are the principal investigator, key personnel, and
any collaborators appropriately trained and well suited to carry out
this work? Is the work proposed appropriate for the experience of the
P.I., key personnel, and any collaborators?
(5) ENVIRONMENT: Does the scientific environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment? Are any collaborative arrangements appropriate? Is there
evidence of institutional support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the
following items will be considered in the determination of scientific
merit and the priority score:
o PROTECTIONS: The adequacy of the proposed protection for humans,
animals, or the environment, to the extent they may be adversely
affected by the project proposed in the application.
o INCLUSION: The adequacy of plans to include subjects from both
genders, all racial and ethnic groups (and subgroups), and children as
appropriate for the scientific goals of the research.
o DATA RELEASE: The adequacy of the proposed plan to release data in
concert with the guidelines stated in this RFA.
o BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: April 13, 2003
Application Receipt Date: May 13, 2003
Peer Review Date: July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 30, 2003
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit, as determined by peer review
o Plans for data release and intellectual property
o Variety in scientific approaches
o Efficiency of scientific approach
o Availability of funds
o Programmatic priorities
REQUIRED FEDERAL CITATIONS
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43).
All investigators proposing clinical research should read the AMENDMENT
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grant0s and Contracts on October 9, 2001
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at http://
grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of
clinical research; updated racial and ethnic categories
in compliance with the new OMB standards; clarification of language
governing NIH-defined Phase III clinical trials consistent with the new
PHS Form 398; and updated roles and responsibilities of NIH staff and
the extramural community. The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must provide a description of plans to
conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy that children (i.e., individuals
under the age of 21) must be included in all human subjects research,
conducted or supported by the NIH, unless there are scientific and
ethical reasons not to include them. This policy applies to all initial
(Type 1) applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
https://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at
https://grants.nih.gov/grants/stem_cells.htm and at
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the applicant to
provide the official NIH identifier(s)for the hESC line(s)to be used in
the proposed research. Applications that do not provide this
information will be returned without review.
PUBLIC 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 public 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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA 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.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation,
Internet addresses (URLs) should not be used to provide information
necessary to 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 authorization
of Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and administered under NIH grants policies described
at https://grants.nih.gov/grants/policy/policy.htm 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
https://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.