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Instructions for Submitting a Proposal for the Sequencing of a New Target Genome
December 31, 2003
Next submission date is January 10, 2005
Summary
With completion of the human genome sequence in April 2003, the National Human Genome Research Institute (NHGRI) entered a new chapter in its quest to more fully understand human genetics, and accordingly released an updated research plan, A Vision for the Future of Genomic Research, (Nature, 422: 835-847. 2003).
One of the major goals in the new plan is to utilize comparative sequence analysis of a diverse set of organisms in order to annotate the human genome and to better understand genome evolution. The NHGRI supports a large-scale sequencing program for these purposes. In order to best determine which sequenced genomes will provide the data needed to address these goals of the comparative sequencing program, NHGRI recently redesigned its procedures for choosing sequencing targets.
Briefly, two working groups will be formed, one in the area of "Annotating the Human Genome" and another in the area of "Comparative Genome Evolution." Each of these working groups has been charged with developing a rationale for choices of target genomes that will address its topic area, along with a prioritized list of specific species. These rationales and lists will be open to change as new or additional scientific information arises. The plans developed by the working groups will be reviewed by a coordinating committee. Background material and a rationale for the new selection process can be found at:
Sequencing Target Organism Selection Procedures
In addition to the two working groups, NHGRI continues to support additional community input as an important part of the new target selection process. Community ideas for specific targets may be proposed to one of the two working groups, depending on the major scientific justifications for sequencing of that target. In cases where a proposal does not fit into either working group mission separate and independent investigator-initiated white papers will continue to be accepted and considered by the coordinating committee, which will assign a priority to the target, or alternately may decide to refer them to one of the working groups.
Based on the above procedures, lists of specific organisms prioritized by the coordinating committee will be approved by the National Advisory Council for Human Genome Research, and approved targets will be sequenced at NHGRI-supported large-scale sequencing centers.
Procedure for Submission of Proposals for Sequencing Genomes
There are some generalities that apply to all consideration of new target organisms for genomic sequencing by NHGRI:
- This program is for consideration of targets for large-scale 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 National Institutes of Health (NIH) programs that provide for the development of such resources.
- This program is intended to have a scope potentially encompassing all organisms except plants, algae, eubacteria and archaea. The primary mission of the NHGRI 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. In addition, other NIH institutes sponsor significant efforts in pathogen genomics. The sequencing of eubacterial, archaeal, algal and plant genomes are more appropriate to the missions of other components of the NIH and/or other agencies. Please see:
- 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:
Individuals wishing to communicate suggestions for sequencing targets directly to one of the two working groups should contact NHGRI staff:
For Annotating the Human Genome:
Dr. Jane Peterson
E-mail: jane_peterson@nih.gov
For Comparative Genome Evolution
Adam Felsenfeld
E-mail: adam_felsenfeld@nih.gov
Note: It is likely that the missions of the working groups will be refined as the process matures.
Working Group I: Annotating the Human Genome
This working group will consider genomic sequences that can be scientifically justified by their usefulness in studies directed toward illuminating the human genome sequence. One important area will be the use of a vertebrate genome sequence (often, but not always that of a mammal) in comparative studies to discover and understand conserved functional elements in the human genome. Such approaches will be critical in identifying new classes of sequence-based functional elements, in cataloguing the complete composition of the human genome sequence with regard to each type of sequence-based functional element, and in understanding the biological function of each sequence-based/specified functional element in the human genome. Another important use to which genomic sequence information will be put is in the analysis of genetic variation, including the variation in the human genome and the variation between the human genome sequence and the sequences of the genomes of closely related species.
It is likely that this group will primarily consider mammalian or perhaps other vertebrate genomes.
Working Group II: Comparative Genome Evolution
This working group will address the acquisition of new genomic sequences for one or more of three main purposes: 1) the provision of sequence from critical phylogenetic positions, for example to illuminate the evolution of major morphogenetic or physiological innovations in evolution; 2) at a smaller evolutionary scale, the provision of sequence from species that will allow the optimal identification of conserved functional regions in the existing genome sequence of important non-mammalian model systems; and 3) the provision of information that addresses basic questions about genome evolution such as evolutionary rates; speciation; genome reorganization, origins of variation, etc.
Submitting White Papers
- The request to have the genome of an organism (or group of organisms) sequenced may be submitted to the NHGRI in the form of a "white paper." The original white paper concept was developed at an NHGRI-sponsored workshop on Developing Guidelines for Choosing New Genomic Sequencing Targets (July 9-10, 2001). While the current working group mechanism described above supercedes the specific recommendations of that workshop, many of the principles remain relevant. The most important difference is that white papers should only be submitted for requests in cases where the major rationale for obtaining genome sequence clearly does not fall into the areas of one of the two working groups described above.
- 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 3, 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.
- 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.
- 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.
- White papers will be accepted twice a year, on January 10 and July 10.
- 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.
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.
- White paper proposals will first receive preliminary assessment by the coordinating committee overseeing the selection process. The coordinating committee will recommend future action in one of the following two ways:
- If the proposed organism meets some or all of the goals of the two working groups ("Annotating the Human Genome" and "Comparative Genome Evolution,") the coordinating committee may recommend that the white paper be submitted for discussion at the next scheduled meeting of the appropriate working group. The working group will then have the option of including the proposed organism in its sequencing plan. It is expected that there will be very few white papers submitted that fall under the purview of either of the working groups since those interested in suggesting such sequencing targets should contact the working groups directly.
- If the proposed organism cannot easily be placed within the scope of either working group but is scientifically meritorious of consideration in its own right, the coordinating committee may review the paper internally. The committee will consider where to include the proposed organism in the prioritized list of sequencing targets. If the coordinating committee believes the nomination is meritorious, it will receive a priority relative to all other candidate organisms. Alternately, the committee may defer deliberations and direct the sequencing centers to obtain preliminary data if that will resolve an outstanding scientific issue. Finally, the committee may also return the proposal unranked. It is important to note that the committee may re-prioritize organisms for sequencing as new candidates are proposed by the community and the working groups. We emphasize that a place on a prioritized list does not guarantee that the organism will be sequenced. Among other things, scientific and programmatic priorities may change during the lifetime of the program. Indeed, part of the intent of this program is to better accommodate changing priorities in a rapidly moving area of research. Submitters of white papers will receive verbal feedback form NHGRI staff.
- As sequencing capacity becomes available, NHGRI large-scale sequencing centers will choose target organisms from the prioritized list. The center Principal Investigator will prepare a detailed plan describing the strategy selected for the sequencing of that particular genome and include a timetable for the determination of the sequence.
Points to Address in a White Paper
A. Specific biological/biomedical rationales for the utility of new sequence data
- Improving human health. How will the genomic sequence of an organism inform our understanding of human disease or hold the potential for improving human health? What, if any, is the relevance to the development of innovative and improved methods of diagnosis, treatment or prevention?
- Informing human biology. How will the genomic sequence of a particular organism lead to a better understanding of biological function in the human?
- Expanding our understanding of basic biological processes relevant to human health, e.g. cell or developmental biology, neurobiology.
- 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.
B. Strategic issues in acquiring new sequence data
- 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?
- 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?
- 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? Will the repeat structure or other biological features pose challenges for genome sequencing? What quality of sequence product is needed (finished sequence? draft? full shotgun?)? What sequencing strategy will be used? Is suitable DNA readily available?
- Are there other (partial) sources of funding available or being sought for this sequencing project? NHGRI is willing to consider requests to sequence disease vectors but priority will be given to requests that relate to the programmatic interests of NHGRI and where co-funding from other entities has either been identified or discussions about such funding is underway.
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 left unmentioned.
White paper submissions that address the above criteria may be submitted via e-mail to:
submission_requests@mail.nih.gov
For additional information about the sequencing program, 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, MD 20852-2033
Phone: (301) 496-7531
Fax: (301) 480-2770
E-mail: jane_peterson@nih.gov or adam_felsenfeld@nih.gov
Last Reviewed: October 2004
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