National Center for Genome Resources
In lieu of individual abstracts,
research projects and investigators at NCGR are represented in this narrative.
More information can be found on the center's Web
Center for Genome Resources (NCGR) is a not-for-profit organization
created to design, develop, support, and deliver resources in support of
public and private genome and genetic research. To accomplish these goals,
NCGR is developing and publishing the Genome Sequence DataBase (GSDB) and
the Genetics and Public Issues (GPI) program.
NCGR is a center to facilitate the flow of information and resources from genome projects into both public and private sectors. A broadly based board of governors provides direction and strategy for the center's development.
NCGR opened in Santa Fe in July 1994, with its initial bioinformatics work being developed through a cooperative 5-year agreement with the Department of Energy funded in July 1995. Committed to serving as a resource for all genomic research, the center workscollaboratively with researchers and seeks input from users to ensure that tools and projects under development meet their needs.
Genome Sequence DataBase
GSDB is a relational database that contains nucleotide sequence data (see pie chart below) and its associated annotation from all known organisms. All data are freely available to the public. The major goals of GSDB are to provide the support structure for storing sequence data and to furnish useful data-retrieval services.
GSDB adheres to the philosophy that the database is a "community-owned" resource that should be simple to update to reflect new discoveries about sequences. A corollary to this is GSDB's conviction that researchers know their areas of expertise much better than a database curator and, therefore, they should be given ownership and control over the data they submit to the database. The true role of the GSDB staff is to help researchers submit data to and retrieve data from the database.
The concept of data ownership is a cornerstone to the functioning of the new GSDB. Every piece of data (e.g., sequence or feature) within the database is owned by the submitting researcher, and changes can be made only by the data owner or GSDB staff. This implementation of data ownership provides GSDB with the ability to support community (third-party) annotationthe addition of annotation to a sequence by other community researchers.
A second enhancement of GSDB is the ability to store and represent sequence alignments. GSDB staff has been constructing alignments to several key sequences including the env and pol (reverse transcriptase) genes of the HIV genome, the complete chromosome VIII of Saccharomyces cerevisiae, and the complete genome of Haemophilus influenzae. These alignments are useful as possible sites of biological interest and for rapidly identifying differences between sequences.
A third key GSDB enhancement is the ability to represent known relationships of order and distance between separate individual pieces of sequence. These sets of sequences and their relative positions are grouped together as a single discontiguous sequence. Such a sequence may be as simple as two primers that define the ends of a sequence tagged site (STS), it may comprise all exons that are part of a single gene, or it may be as complex as the STS map for an entire chromosome.
GSDB staff has constructed discontiguous sequences for human chromosomes 1 through 22 and X that include markers from Massachusetts Institute of TechnologyWhitehead Institute STS maps and from the Stanford Human Genome Center. The set of 2000 STS markers for chromosome X, which were mapped recently by Washington University at St.Louis, also have been added to chromosome X. About 50 genomic sequences have been added to the chromosome 22 map by determining their overlap with STS markers. Genomic sequences are being added to all the chromosomes as their overlap with the STS markers is determined. These discontiguous sequences can be retrieved easily and viewed via their sequence names using the GSDB Annotator. Sequence names follow the format of HUMCHR#MP, where # equals 1 through 22 or X.
GSDB staff also has utilized discontiguous sequences to construct maps for maize and rice. The maize discontiguous sequences were constructed using markers from the University of Missouri, Columbia. Markers for the rice discontiguous sequence were obtained from the Rice Genome Database at Cornell University and the Rice Genome Research Project in Japan.
Annotator displays a sequence and its associated biological information as an image, with the scale of the image adjustable by the user. Additional information about the sequence or an associate biological feature can be obtained in a pop-up window. Annotator also allows a user to retrieve a sequence for review, edit existing data, or add annotation to the record. Sequences can be created using Annotator, and any sequences created or edited can be saved either to a local file for later review and further editing or saved directly to the database.
Correct database structures are important for storing data and providing the research community with tools for searching and retrieving data. GSDB is making a concerted effort to expand and improve these services. The first generation of the Maestro query tool is available from the GSDB Web pages. Maestro allows researchers to perform queries on 18 different fields, some of which are queryable only through GSDB, for example, D segment numbers from the Genome Database at Johns Hopkins University in Baltimore.
Additionally, Maestro allows queries with mixed Boolean operators for a more refined search. For example, a user may wish to compare relatively long mouse and human sequences that do not contain identified coding regions. To obtain all sequences meeting these criteria, the scientific name field would be searched first for "Mus musculus" and then for "Homo sapiens" using the Boolean term "OR." Then the sequence-length filter could be used to refine the search to sequences longer than 10,000 base pairs. To exclude sequences containing identified coding-region features, the "BUT NOT" term can be used with the Feature query field set equal to "coding region."
With Maestro, users can view the list of search matches a few at a time and retrieve more of the list as needed. From the list, users can select one or several sequences according to their short descriptions and review or download the sequence information in GIO, FASTA, or GSDB flatfile format.
Microbial Genome WebPages
NCGR also maintains informational Web pages on microbial genomes. These pages, created as a community reference, contain a list of current or completed eubacterial, Archaeal, and eukaryotic genome sequencing projects. Each main page includes the name of he organism being sequenced, sequencing groups involved, background information on the organism, and its current location on the Carl Woese Tree of Life. As the Microbial Genome Project progresses, the pages will be updated as appropriate.
Genetics and Public Issues Program
GPI serves as a crucial resource for people seeking information and making decisions about genetics or genomics. GPI develops and provides information that explains the ethical, legal, policy, and social relevance of genetic discoveries and applications.
To achieve its mission, GPI has set forth three goals: (1) preparation and development of resources, including careful delineation of ethical, legal, policy, and social issues in genetics and genomics; (2) dissemination of genetic information targeted to the public, legal and health professionals, policymakers, and decision makers; and (3) creation of an information network to facilitate interaction among groups.
GPI delivers information through four primary vehicles: online resources, conferences, publications, and educational programs. The GPI program maintains a continually evolving World Wide Web site containing a range of material freely accessible over the Internet.
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