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 (https://www.genome.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: (https://www.genome.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 (https://www.genome.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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