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Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp.
Entrez Gene is the gene-specific database at the National Center for Biotechnology Information (NCBI), a division of the National Library of Medicine (NLM), located on the campus of the US National Institutes of Health (NIH) in Bethesda, MD, USA. Entrez Gene provides unique integer identifiers for genes and other loci (such as officially named mapped markers) for a subset of model organisms. It tracks those identifiers, and is integrated with the Entrez system for interactive query, LinkOut and access by E-Utilities (1). The information that is maintained includes nomenclature, defining sequence, chromosomal localization, gene products and their attributes (e.g. protein interactions), associated markers, phenotypes, interactions and a wealth of links to citations, related sequences, variation, maps, expression, homologs, protein domain content and external databases.
Data in Entrez Gene result from a mixture of curation by RefSeq staff and automated analyses. Annotation in sequences from NCBI's Reference sequence project (2) or the International Nucleotide Sequence Database Collaboration (DDBJ, EMBL, GenBank) (3) is integrated with information from collaborating model organism databases, public users and literature review (especially the Gene References into Function or GeneRIFs).
Entrez Gene is an integral part of representation of gene-specific information at NCBI. The information conveyed by establishing the relationship between sequence and a GeneID is used by other NCBI resources (1) such as BLAST, dbSNP, GEO, HomoloGene, Map Viewer, Probe, UniGene, UniSTS and NCBI's genome annotation pipeline. For example, the names associated with GeneIDs are used in HomoloGene, UniGene and the Mammalian Gene Collection (4). Inconsistencies in representation of genes and their sequences are investigated, and resolved by NCBI RefSeq staff in consultation with multiple authorities (2). Although providing a stable interface is a goal of Entrez Gene, the content, display or methods for bulk transfer may change. One method to receive advanced notification of changes is via subscription to gene-announce/at/ncbi.nlm.nih.gov.
The primary goals of Entrez Gene are to provide tracked, unique identifiers for genes of multiple genomes and to report information associated with those identifiers for unrestricted public use. The identifier that is assigned (GeneID) is an integer, and is species-specific. In other words, the integer assigned to dystrophin in human is different from that in any other species. The GeneID is reported in RefSeq records as a ‘db_xref’ (e.g. /db_xref=‘GeneID:856646’, in GenBank format).
Entrez Gene provides multiple reports. For the interactive user, the defaults are the HTML summary display resulting from an Entrez query (Figure 1) or a gene-specific report accessed by clicking on the symbol in the summary page (Figure 2). The Gene Table display option is useful to obtain a report of the intron/exon organization of the gene as annotated on a RefSeq genomic sequence, and to navigate quickly to the sequence of any of those gene features. In addition to the standard views from Entrez, Gene provides a complete database extraction as well as several special reports for ftp transfer (ftp://ftp.ncbi.nih.gov/gene/README). The data are also available from the programatic interface to Entrez, namely E-Utilities (1).
Identifiers are always assigned to what is annotated as a gene feature on a RefSeq record. Identifiers may also be assigned when no RefSeq exists. This may occur when an authoritative source for a genome, such as a model organism-specific database, assigns an identifier to what is termed a gene, mapped locus or trait, even though that entity is not completely defined by sequence. When a Gene record is established, it is assigned a category (e.g. protein-coding, pseudogene, rRNA, unknown). The term ‘unknown’ is used when the category is under review, as when some of the sequences defining the gene are annotated with coding regions, but the support for that annotation is inconclusive. The assigned category can change without changing the GeneID.
As of September, 2006, there were >2 million current records in Gene, distributed among >3500 taxa (Table 1). Not all the taxa are completely represented in Gene; most of the eukaryotes, for example, have Gene records only for their mitochondrial genomes. The Gene Statistics site (http://www.ncbi.nlm.nih.gov/projects/Gene/gentrez_stats.cgi) reports both current and historical counts of records by taxonomic node and species.
Figure 2 displays representative gene-specific information that can be retrieved through Entrez Gene. For example, GeneRIFs, contributed by the general public and the Index Section of the National Library of Medicine, provide an annotated bibliography of the function, discovery and mapping of genes from the current literature. Not all categories of information are displayed completely in the Gene Report; many details may be retrieved by links (Links menu, Figure 2a) provided to other databases such as Nucleotide and Protein for sequence, HomoloGene for integration of information about homologs, Map Viewer for extended genomic context and comparative maps, GENSAT, UniGene and GEO for expression data, Conserved Domain Database for domain content of proteins, OMIM for human Mendelian disorders, PubMed and Books for publications, species-specific databases and LinkOut link for navigation to external databases that have reported they have more information related to a GeneID. Links are also provided to tools such as BLink (1), which supports many views of related proteins determined by BLAST alignments. The goal is to integrate sufficient text, keywords and links to make Entrez Gene an effective starting place to retrieve information of interest.
The information in Entrez Gene can be accessed in multiple ways at NCBI (Table 2). The most direct is to submit a query to Entrez from the NCBI home page and display the results in Gene, or enter a query in any Entrez query bar and restrict the database search to Gene. Another way is to take advantage of the Links computed by the Entrez system. For example, you might find a PubMed record of interest and from PubMed's Links menu discover that there is a record in Entrez Gene connected to the publication. The BLAST group uses the GeneID<->sequence relationship maintained by Entrez Gene to help you navigate from protein or mRNA accessions matching your query to Entrez Gene via the blue G icon. Map Viewer provides links from annotated genes to Entrez Gene. And RefSeq records include the GeneID as a db_xref in the gene feature. Thus you can navigate to Gene not only by text but by genomic position (Map Viewer), RefSeq annotation and sequence data (BLAST, Nucleotide, Protein).
If you register for MyNCBI (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=helpmyncbi.chapter.MyNCBI), you can elect to receive e-mails when records satisfying your favorite search are created or updated. You can also customize your default display to identify what subset of records returned by a query has particular attributes (Figure 1).
Entrez Gene can serve as a directory to gene-specific information for databases outside of NCBI. There are two major categories of connections. One comes from active collaborations with multiple data providers such as model organism databases, the GO consortium, KEGG and Reactome (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=helpgene.table.EntrezGene.T1). The others are generated from data providers who register with the NCBI LinkOut (1) system. Any user of Entrez Gene retrieving a record with a LinkOut will then be able to connect to the registered database according to the specification of the data provider.
We welcome your feedback with respect to the Entrez Gene interface, or any data contained therein. Please select from the Feedback options on any Gene page (Figure 1).
Funding to pay the Open Access publication charges for this article was provided by NIH.
Conflict of interest statement. None declared.