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1.  RefSeq: an update on mammalian reference sequences 
Nucleic Acids Research  2013;42(Database issue):D756-D763.
The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of annotated genomic, transcript and protein sequence records derived from data in public sequence archives and from computation, curation and collaboration (http://www.ncbi.nlm.nih.gov/refseq/). We report here on growth of the mammalian and human subsets, changes to NCBI’s eukaryotic annotation pipeline and modifications affecting transcript and protein records. Recent changes to NCBI’s eukaryotic genome annotation pipeline provide higher throughput, and the addition of RNAseq data to the pipeline results in a significant expansion of the number of transcripts and novel exons annotated on mammalian RefSeq genomes. Recent annotation changes include reporting supporting evidence for transcript records, modification of exon feature annotation and the addition of a structured report of gene and sequence attributes of biological interest. We also describe a revised protein annotation policy for alternatively spliced transcripts with more divergent predicted proteins and we summarize the current status of the RefSeqGene project.
doi:10.1093/nar/gkt1114
PMCID: PMC3965018  PMID: 24259432
2.  Current status and new features of the Consensus Coding Sequence database  
Nucleic Acids Research  2013;42(Database issue):D865-D872.
The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets.
doi:10.1093/nar/gkt1059
PMCID: PMC3965069  PMID: 24217909
3.  Comparison of RefSeq protein-coding regions in human and vertebrate genomes 
BMC Genomics  2013;14:654.
Background
Advances in high-throughput sequencing technology have yielded a large number of publicly available vertebrate genomes, many of which are selected for inclusion in NCBI’s RefSeq project and subsequently processed by NCBI’s eukaryotic annotation pipeline. Genome annotation results are affected by differences in available support evidence and may be impacted by annotation pipeline software changes over time. The RefSeq project has not previously assessed annotation trends across organisms or over time. To address this deficiency, we have developed a comparative protocol which integrates analysis of annotated protein-coding regions across a data set of vertebrate orthologs in genomic sequence coordinates, protein sequences, and protein features.
Results
We assessed an ortholog dataset that includes 34 annotated vertebrate RefSeq genomes including human. We confirm that RefSeq protein-coding gene annotations in mammals exhibit considerable similarity. Over 50% of the orthologous protein-coding genes in 20 organisms are supported at the level of splicing conservation with at least three selected reference genomes. Approximately 7,500 ortholog sets include at least half of the analyzed organisms, show highly similar sequence and conserved splicing, and may serve as a minimal set of mammalian “core proteins” for initial assessment of new mammalian genomes. Additionally, 80% of the proteins analyzed pass a suite of tests to detect proteins that lack splicing conservation and have unusual sequence or domain annotation. We use these tests to define an annotation quality metric that is based directly on the annotated proteins thus operates independently of other quality metrics such as availability of transcripts or assembly quality measures. Results are available on the RefSeq FTP site [http://ftp.ncbi.nlm.nih.gov/refseq/supplemental/ProtCore/SM1.txt].
Conclusions
Our multi-factored analysis demonstrates a high level of consistency in RefSeq protein representation among vertebrates. We find that the majority of the RefSeq vertebrate proteins for which we have calculated orthology are good as measured by these metrics. The process flow described provides specific information on the scope and degree of conservation for the analyzed protein sequences and annotations and will be used to enrich the quality of RefSeq records by identifying targets for further improvement in the computational annotation pipeline, and by flagging specific genes for manual curation.
doi:10.1186/1471-2164-14-654
PMCID: PMC3882889  PMID: 24063302
Genome annotation; RefSeq proteins; Protein quality assessment; Splice orthologs
4.  Recent advances in biocuration: Meeting Report from the fifth International Biocuration Conference 
The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration’s (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest.
doi:10.1093/database/bas036
PMCID: PMC3483532  PMID: 23110974
5.  Tracking and coordinating an international curation effort for the CCDS Project 
The Consensus Coding Sequence (CCDS) collaboration involves curators at multiple centers with a goal of producing a conservative set of high quality, protein-coding region annotations for the human and mouse reference genome assemblies. The CCDS data set reflects a ‘gold standard’ definition of best supported protein annotations, and corresponding genes, which pass a standard series of quality assurance checks and are supported by manual curation. This data set supports use of genome annotation information by human and mouse researchers for effective experimental design, analysis and interpretation. The CCDS project consists of analysis of automated whole-genome annotation builds to identify identical CDS annotations, quality assurance testing and manual curation support. Identical CDS annotations are tracked with a CCDS identifier (ID) and any future change to the annotated CDS structure must be agreed upon by the collaborating members. CCDS curation guidelines were developed to address some aspects of curation in order to improve initial annotation consistency and to reduce time spent in discussing proposed annotation updates. Here, we present the current status of the CCDS database and details on our procedures to track and coordinate our efforts. We also present the relevant background and reasoning behind the curation standards that we have developed for CCDS database treatment of transcripts that are nonsense-mediated decay (NMD) candidates, for transcripts containing upstream open reading frames, for identifying the most likely translation start codons and for the annotation of readthrough transcripts. Examples are provided to illustrate the application of these guidelines.
Database URL: http://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi
doi:10.1093/database/bas008
PMCID: PMC3308164  PMID: 22434842
6.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2011;40(Database issue):D13-D25.
In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Website. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe, Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
doi:10.1093/nar/gkr1184
PMCID: PMC3245031  PMID: 22140104
7.  BioProject and BioSample databases at NCBI: facilitating capture and organization of metadata 
Nucleic Acids Research  2011;40(Database issue):D57-D63.
As the volume and complexity of data sets archived at NCBI grow rapidly, so does the need to gather and organize the associated metadata. Although metadata has been collected for some archival databases, previously, there was no centralized approach at NCBI for collecting this information and using it across databases. The BioProject database was recently established to facilitate organization and classification of project data submitted to NCBI, EBI and DDBJ databases. It captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. Concomitantly, the BioSample database is being developed to capture descriptive information about the biological samples investigated in projects. BioProject and BioSample records link to corresponding data stored in archival repositories. Submissions are supported by a web-based Submission Portal that guides users through a series of forms for input of rich metadata describing their projects and samples. Together, these databases offer improved ways for users to query, locate, integrate and interpret the masses of data held in NCBI's archival repositories. The BioProject and BioSample databases are available at http://www.ncbi.nlm.nih.gov/bioproject and http://www.ncbi.nlm.nih.gov/biosample, respectively.
doi:10.1093/nar/gkr1163
PMCID: PMC3245069  PMID: 22139929
8.  NCBI Reference Sequences (RefSeq): current status, new features and genome annotation policy 
Nucleic Acids Research  2011;40(Database issue):D130-D135.
The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of genomic, transcript and protein sequence records. These records are selected and curated from public sequence archives and represent a significant reduction in redundancy compared to the volume of data archived by the International Nucleotide Sequence Database Collaboration. The database includes over 16 000 organisms, 2.4 × 106 genomic records, 13 × 106 proteins and 2 × 106 RNA records spanning prokaryotes, eukaryotes and viruses (RefSeq release 49, September 2011). The RefSeq database is maintained by a combined approach of automated analyses, collaboration and manual curation to generate an up-to-date representation of the sequence, its features, names and cross-links to related sources of information. We report here on recent growth, the status of curating the human RefSeq data set, more extensive feature annotation and current policy for eukaryotic genome annotation via the NCBI annotation pipeline. More information about the resource is available online (see http://www.ncbi.nlm.nih.gov/RefSeq/).
doi:10.1093/nar/gkr1079
PMCID: PMC3245008  PMID: 22121212
9.  Solving the Problem: Genome Annotation Standards before the Data Deluge 
Standards in Genomic Sciences  2011;5(1):168-193.
The promise of genome sequencing was that the vast undiscovered country would be mapped out by comparison of the multitude of sequences available and would aid researchers in deciphering the role of each gene in every organism. Researchers recognize that there is a need for high quality data. However, different annotation procedures, numerous databases, and a diminishing percentage of experimentally determined gene functions have resulted in a spectrum of annotation quality. NCBI in collaboration with sequencing centers, archival databases, and researchers, has developed the first international annotation standards, a fundamental step in ensuring that high quality complete prokaryotic genomes are available as gold standard references. Highlights include the development of annotation assessment tools, community acceptance of protein naming standards, comparison of annotation resources to provide consistent annotation, and improved tracking of the evidence used to generate a particular annotation. The development of a set of minimal standards, including the requirement for annotated complete prokaryotic genomes to contain a full set of ribosomal RNAs, transfer RNAs, and proteins encoding core conserved functions, is an historic milestone. The use of these standards in existing genomes and future submissions will increase the quality of databases, enabling researchers to make accurate biological discoveries.
doi:10.4056/sigs.2084864
PMCID: PMC3236044  PMID: 22180819
10.  Entrez Gene: gene-centered information at NCBI 
Nucleic Acids Research  2010;39(Database issue):D52-D57.
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)’s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI’s Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI’s Entrez system, via NCBI’s Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.
doi:10.1093/nar/gkq1237
PMCID: PMC3013746  PMID: 21115458
11.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2010;39(Database issue):D38-D51.
In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS, Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
doi:10.1093/nar/gkq1172
PMCID: PMC3013733  PMID: 21097890
12.  Short Communication: Cataloguing the HIV Type 1 Human Protein Interaction Network 
AIDS Research and Human Retroviruses  2008;24(12):1497-1502.
Abstract
Although many interactions between HIV-1 and human proteins have been reported in the scientific literature, no publicly accessible source for efficiently reviewing this information was available. Therefore, a project was initiated in an attempt to catalogue all published interactions between HIV-1 and human proteins. HIV-related articles in PubMed were used to develop a database containing names, Entrez GeneIDs, and RefSeq protein accession numbers of interacting proteins. Furthermore, brief descriptions of the interactions, PubMed identification numbers of articles describing the interactions, and keywords for searching the interactions were incorporated. Over 100,000 articles were reviewed, resulting in the identification of 1448 human proteins that interact with HIV-1 comprising 2589 unique HIV-1-to-human protein interactions. Preliminary analysis of the extracted data indicates 32% were direct physical interactions (e.g., binding) and 68% were indirect interactions (e.g., up-regulation through activation of signaling pathways). Interestingly, 37% of human proteins in the database were found to interact with more than one HIV-1 protein. For example, the signaling protein mitogen-activated protein kinase 1 has a surprising range of interactions with 10 different HIV-1 proteins. Moreover, large numbers of interactions were published for the HIV-1 regulatory protein Tat and envelope proteins: 30% and 33% of total interactions identified, respectively. The database is accessible at http://www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions/ and is cross-linked to other National Center for Biotechnology Information databases and programs via Entrez Gene. This database represents a unique and continuously updated scientific resource for understanding HIV-1 replication and pathogenesis to assist in accelerating the development of effective therapeutic and vaccine interventions.
doi:10.1089/aid.2008.0113
PMCID: PMC2655106  PMID: 19025396
13.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2009;38(Database issue):D5-D16.
In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, Reference Sequence, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Peptidome, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
doi:10.1093/nar/gkp967
PMCID: PMC2808881  PMID: 19910364
15.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2008;37(Database issue):D5-D15.
In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the web applications is custom implementation of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
doi:10.1093/nar/gkn741
PMCID: PMC2686545  PMID: 18940862
16.  NCBI Reference Sequences: current status, policy and new initiatives 
Nucleic Acids Research  2008;37(Database issue):D32-D36.
NCBI's Reference Sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) is a curated non-redundant collection of sequences representing genomes, transcripts and proteins. RefSeq records integrate information from multiple sources and represent a current description of the sequence, the gene and sequence features. The database includes over 5300 organisms spanning prokaryotes, eukaryotes and viruses, with records for more than 5.5 × 106 proteins (RefSeq release 30). Feature annotation is applied by a combination of curation, collaboration, propagation from other sources and computation. We report here on the recent growth of the database, recent changes to feature annotations and record types for eukaryotic (primarily vertebrate) species and policies regarding species inclusion and genome annotation. In addition, we introduce RefSeqGene, a new initiative to support reporting variation data on a stable genomic coordinate system.
doi:10.1093/nar/gkn721
PMCID: PMC2686572  PMID: 18927115
17.  Human immunodeficiency virus type 1, human protein interaction database at NCBI 
Nucleic Acids Research  2008;37(Database issue):D417-D422.
The ‘Human Immunodeficiency Virus Type 1 (HIV-1), Human Protein Interaction Database’, available through the National Library of Medicine at www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions, was created to catalog all interactions between HIV-1 and human proteins published in the peer-reviewed literature. The database serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. To facilitate this discovery approach, the following information for each HIV-1 human protein interaction is provided and can be retrieved without restriction by web-based downloads and ftp protocols: Reference Sequence (RefSeq) protein accession numbers, Entrez Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. Currently, 2589 unique HIV-1 to human protein interactions and 5135 brief descriptions of the interactions, with a total of 14 312 PMID references to the original articles reporting the interactions, are stored in this growing database. In addition, all protein–protein interactions documented in the database are integrated into Entrez Gene records and listed in the ‘HIV-1 protein interactions’ section of Entrez Gene reports. The database is also tightly linked to other databases through Entrez Gene, enabling users to search for an abundance of information related to HIV pathogenesis and replication.
doi:10.1093/nar/gkn708
PMCID: PMC2686594  PMID: 18927109
18.  What everybody should know about the Rat Genome and its online resources 
Nature genetics  2008;40(5):523-527.
It has been four years since the rat genome’s original publication. Five groups are working together to assemble, annotate and release the next version of the genome for this key model system. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat’s genomic resources to keep pace with the rat’s prominence in the laboratory. In this commentary we describe the current status of the rat genome sequence and the plans for its impending ‘upgrade’. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, NCBI’s RefSeq and Genes databases, UCSC’s Genome Browser and RGD’s disease portals for cardiovascular disease and obesity.
doi:10.1038/ng0508-523
PMCID: PMC2505193  PMID: 18443589
19.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2007;36(Database issue):D13-D21.
In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data available through NCBI's web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link, Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace, Assembly, and Short Read Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Database of Genotype and Phenotype, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting the web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
doi:10.1093/nar/gkm1000
PMCID: PMC2238880  PMID: 18045790
20.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2006;35(Database issue):D5-D12.
In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link(BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace and Assembly Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Viral Genotyping Tools, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at .
doi:10.1093/nar/gkl1031
PMCID: PMC1781113  PMID: 17170002
21.  Entrez Gene: gene-centered information at NCBI 
Nucleic Acids Research  2006;35(Database issue):D26-D31.
Entrez 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.
doi:10.1093/nar/gkl993
PMCID: PMC1761442  PMID: 17148475
22.  NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins 
Nucleic Acids Research  2006;35(Database issue):D61-D65.
NCBI's reference sequence (RefSeq) database () is a curated non-redundant collection of sequences representing genomes, transcripts and proteins. The database includes 3774 organisms spanning prokaryotes, eukaryotes and viruses, and has records for 2 879 860 proteins (RefSeq release 19). RefSeq records integrate information from multiple sources, when additional data are available from those sources and therefore represent a current description of the sequence and its features. Annotations include coding regions, conserved domains, tRNAs, sequence tagged sites (STS), variation, references, gene and protein product names, and database cross-references. Sequence is reviewed and features are added using a combined approach of collaboration and other input from the scientific community, prediction, propagation from GenBank and curation by NCBI staff. The format of all RefSeq records is validated, and an increasing number of tests are being applied to evaluate the quality of sequence and annotation, especially in the context of complete genomic sequence.
doi:10.1093/nar/gkl842
PMCID: PMC1716718  PMID: 17130148
23.  Database resources of the National Center for Biotechnology Information 
Nucleic Acids Research  2005;34(Database issue):D173-D180.
In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Retroviral Genotyping Tools, HIV-1, Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at: .
doi:10.1093/nar/gkj158
PMCID: PMC1347520  PMID: 16381840
24.  NCBI Reference Sequence Project: update and current status 
Nucleic Acids Research  2003;31(1):34-37.
The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single best non-redundant and comprehensive collection of naturally occurring biological molecules, representing the central dogma. Nucleotide and protein sequences are explicitly linked on a residue-by-residue basis in this collection. Ideally all molecule types will be available for each well-studied organism, but the initial database collection pragmatically includes only those molecules and organisms that are most readily identified. Thus different amounts of information are available for different organisms at any given time. Furthermore, for some organisms additional intermediate records are provided when the genome sequence is not yet finished. The collection is supplied by NCBI through three distinct pipelines in addition to collaborations with community groups. The collection is curated on an ongoing basis. Additional information about the NCBI RefSeq project is available at http://www.ncbi.nih.gov/RefSeq/.
PMCID: PMC165558  PMID: 12519942
25.  RefSeq and LocusLink: NCBI gene-centered resources 
Nucleic Acids Research  2001;29(1):137-140.
Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish. RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation. Additional information about LocusLink and RefSeq is available at http://www.ncbi.nlm.nih.gov/LocusLink/.
PMCID: PMC29787  PMID: 11125071

Results 1-25 (26)