OPPORTUNITY TO PROPOSE ORGANISMS FOR GENOMIC SEQUENCING

Release Date:  December 18, 2001

NOTICE:  NOT-HG-02-003

National Human Genome Research Institute

Annual submission dates:  February 10, June 10 and October 10

With the achievement of the initial objectives of the HGP, interest in 
sequencing the genomes of additional organisms has grown enormously. 
Accordingly, the National Human Genome Research Institute (NHGRI) believes 
that it is now appropriate to implement a competitive process in which the 
selection of genomes to sequence using NHGRI-supported sequencing capacity is 
based on investigator or community-initiated proposals and peer review. This 
document describes a systematic process that NHGRI is implementing to 
encourage focus on the scientific issues to be addressed by new sequence 
data. This will allow all investigators, the sequencers, and the NHGRI to 
participate in a process for selecting new organisms for genomic sequencing 
on the basis of specific, well-defined scientific goals, taking advantage of 
the rigor and robustness provided by scientific discussion and peer 
evaluation.

As of October 1, 2001, the following procedure will apply to all requests to 
use NHGRI-supported capacity for the sequencing of the genome of any new 
organism, i.e. one for which sequencing has not yet been initiated. This 
procedure applies to:

Requests for NHGRI support for sequencing.

While other agencies and organizations that provide support for large-scale 
DNA sequencing (e.g. other NIH institutes, other U.S., foreign or 
international agencies) may choose to adopt some or all of these ideas and 
procedures, separate inquiries should be made directly to those agencies.

Requests for sequencing of all organisms except eubacteria, archaea and 
plants. 

The NHGRI is a component of the National Institutes of Health. Accordingly, 
its primary mission is to develop and apply the techniques of genomics and 
large-scale biology to the improvement of human health and to the expansion 
of scientific understanding that will lead to the improvement of human 
health. The sequencing of eubacterial, archaeal, and plant genomes are more 
appropriate to the missions of other components of the NIH and/or other 
agencies.

Requests for genomic sequencing.

Proposals for EST sequencing, full-length cDNA sequencing, or the development 
of other genomic resources will not be considered by this procedure. There 
are a number of other NHGRI and NIH programs that provide for the development 
of such other resources, see, for example, the web sites of: 
The NIH Non-Mammialian Models Committee 
(http://www.nih.gov/science/models/process/index.html)
The Mammalian Gene Collection (http://mgc.nci.nih.gov/)
The Trans-NIH BAC sequencing program 
(http://www.nih.gov/science/models/mouse/index.html)

Data release. All genomic sequence data generated under NHGRI support will be 
made available without restriction, in accordance with the NHGRI policy on 
rapid release of large-scale genomic sequence data to the research community 
(http://www.nhgri.nih.gov:80/Grant_info/Funding/Statements/RFA/data_release.html).

Procedure:

1. The request to have the genome of an organism (or group of organisms) 
sequenced must be submitted to the NHGRI in the form of a "white paper." The 
white paper concept was developed at a recent NHGRI-sponsored workshop on 
"Developing Guidelines for Choosing New Genomic Sequencing Targets" (July 9-
10, 2001) and more information about the discussions leading to the 
development of the concept can be found in the Workshop Summary: 
(http://www.nhgri.nih.gov/About_NHGRI/Der/org_request/workshop_summary.html).

a. The white paper should present a clear justification for the sequencing of 
the organism (or group of organisms). There are several factors that will 
influence the selection of a new organism for genomic sequencing, these 
factors fall into two distinct groups. One is biological and includes 
considerations of the ways in which the sequence information will contribute 
to advances in biomedical and biological research. The second is strategic 
and concerns pragmatic issues that are relevant to sequence acquisition. Both 
sets of factors (see item 6, Points to Address, below) must be addressed in 
the white paper to effectively allow the review process (see item 2) to 
establish the priority for obtaining the sequence of an organism on a cost-
benefit basis.

b. The white paper should discuss the relevant scientific community"s depth 
of interest in
having the sequence of the particular organism, and should describe any 
process, if there has been one, by which that research community has come to 
consensus on the request being made.

c. A white paper may be submitted by a sequencing center, by a collaborative 
group involving both a sequencing center and a research community or an 
individual, or by a research community or individual that has not already 
made a connection with a specific sequencing center. In the latter case, the 
paper should describe any efforts that have been made to contact sequencing 
centers.

d. White papers will be accepted three times a year, on October 10, February 
10, and June 10.

e. The white paper should not exceed a total of ten pages. There is no 
specific form necessary for submission of a white paper nor is any specific 
format required, but all of the issues listed in item 6 should be addressed. 
The white paper should be submitted by e-mail to: 
sequencing_requests@mail.nih.gov. Although not a criterion for consideration 
by NHGRI, the developer(s) of a white paper is (are) also encouraged to 
disseminate it and/or its ideas broadly within the scientific community. For 
example, the white paper may be published or made available through a web 
site or list serve. Such dissemination will not in any way compromise the 
consideration of the request by the NHGRI.

1. The white paper proposals will be assessed by a review committee organized 
by NHGRI program staff for this purpose. The committee will recommend a 
sequencing priority for the organism. The assessment process will NOT involve 
the regular NIH peer review system.

a. That committee will be composed of five permanent members, including at 
least two members of the National Advisory Council for Human Genome Research 
(one of whom will chair it) and any ad hoc reviewers who might be needed. The 
membership will be posted at: Panel Membership 
(http://www.nhgri.nih.gov/About_NHGRI/Der/org_request/panel_memb.html).

b. For each organism proposed where the case is considered compelling, the 
committee will assign a priority for sequencing on a scale of 1 (the highest) 
to 3, based on the criteria listed under 6a and b (below). If the white paper 
does not present enough information for the committee to make a decision, the 
committee can ask the proposer to submit a revised white paper. In some 
instances, however, the committee may consider the evidence and decide that 
the organism should not be considered for sequencing with NHGRI funds at 
this time.

c. The committee"s decisions will be reported by the committee chair at the 
next meeting of the National Advisory Council for Human Genome Research. The 
Council will review the committee"s recommendations of priority assignments. 
If there is disagreement between the committee"s assessment of priority and 
the Council"s, the committee will be notified of the Council"s opinion at the 
committee"s next meeting. The committee may re-discuss the issue and may ask 
the proposer for more information.

3. Twice a year, at the times of its semi-annual progress reports, each 
NHGRI-supported large- scale sequencing center will provide NHGRI staff with 
a projection of its sequencing capacity (restricted to the capacity supported 
by NHGRI funds). The projections will be on a monthly basis, will extend for 
the subsequent two years, and will include estimates of total read capacity, 
read capacity committed to current projects, available (currently 
uncommitted) read capacity.

4. When a center determines that it is ready to commit to a new sequencing 
project [taking into account the necessary lead time, which will differ 
depending on certain characteristics (especially genome size) of the 
particular organism being considered], the center P.I. and NHGRI staff will 
negotiate the center"s next sequencing target from the Review 
Committee/Council-approved priority list.

5. When a choice has been made, the center P.I. will prepare a detailed plan 
for generating the sequence. The plan will describe the strategy selected for 
the sequencing of that particular genome and include a timetable for the 
determination of the sequence. The plan will be reviewed by the Sequencing 
Advisory Panel (SAP) of the NHGRI"s Research Network for Large-scale 
Sequencing. Approval by the SAP will be necessary and sufficient for the 
sequencing project to begin.

6. Points to Address in a White Paper

A. Specific biological rationales for the utility of new sequence data

1. Improving human health. How will the genomic sequence of an organism 
inform our understanding of human health and disease? What, if any, is the 
relevance to the development of innovative and improved methods of diagnosis, 
treatment or prevention?

2. Informing human biology. How will the genomic sequence of a particular 
organism lead to a better understanding of biological function in the human?

Informing the human sequence. How will the genomic sequence of a particular 
organism
lead to a better description of the functions of specific sequence features 
of the human genome?

3. Providing a better connection between the sequences of non-human organisms 
and the
human sequence. How will the genomic sequence of a particular organism 
increase our ability to identify orthologs in the sequences of well-studied 
model organisms and how will that deepen our understanding of the human 
sequence?

4. Expanding our understanding of basic biological processes relevant to 
human health, e.g. developmental biology, neurobiology.

5. Providing additional surrogate systems for human experimentation, e.g. new 
disease models, improved opportunities for drug testing, or other medical 
procedures, such as transplantation.

Facilitating the ability to do experiments, e.g "direct" genetics or 
positional mapping, in additional organisms.

3.	Expanding our understanding of evolutionary processes (biological 
innovation, selection) in general, and human evolution in particular.

B. Strategic issues in acquiring new sequence data

1. The demand for the new sequence data. What is the size of the research 
community that will use it? What is the community"s enthusiasm for having the 
sequence? Will the new sequence data stimulate the expansion of the research 
community? The suitability of the organism for experimentation. What are the 
basic properties of the organism that affect its ability to be studied in the 
laboratory (e.g. availability, ability to be cultured and propagated in the 
laboratory, generation time)? Are
 mutants available with defined phenotypes? How will the new sequence data 
enhance the experimental use of the organism? What other genomic resources 
and technologies (e.g. gene transfer, ability to go from molecule to 
mutation) are available that will allow the new sequence information to be 
effectively used?

2. The rationale for the complete sequence of the organism. Why would the 
complete sequence be more useful than the sequences of specific regions, or 
only the coding sequences, or only ESTs? Are there alternative ways to get 
the necessary information?

4. The cost of sequencing the genome and the state of readiness of the 
organism"s DNA for sequencing. What is the size of the genome? What quality 
of sequence product is needed (finished sequence? draft? Full shotgun?)? What 
sequencing strategy will be used? Is suitable DNA readily available?

5. Are there other (partial) sources of funding available or being sought for 
this sequencing project? All proposals of new organisms for genomic 
sequencing by the NHGRI-supported sequencing centers must address both sets 
of issues. If one or more of the issues listed above is not applicable to the 
specific request that should be stated clearly rather than not mentioned.

For additional information about the process for selecting organisms for 
genomic sequencing, please contact:

Dr. Jane Peterson or Dr. Adam Felsenfeld
Program Directors, Large-scale Sequencing
National Human Genome Research Institute
Building 31, Room B2B07
MSC 2033
National Institutes of Health
9000 Rockville Pike
Bethesda, Maryland  20852-2033
Phone:  (301) 496-7531
Fax:  (301) 480-2770
e-mail:  jane_peterson@nih.gov or adam_felsenfeld@nih.gov



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