• What's New - recently released resources and enhancements to existing resources.

• NCBI News - announcements about new resources, enhancements to existing resources, staff publications, tutorials, FAQs.

• NCBI Announcements Email Lists - Receive announcements about changes and updates to a variety of NCBI services. In addition to a general NCBI-announce list, topic-specific e-mail lists are available for BLAST, GenBank, dbSNP, Genomes, LinkOut, RefSeq, Sequin, and Entrez Utilities (for making WWW Links to Entrez). Follow the link to the NCBI Announcements Email Lists page to see a complete list of available topics. Information on how to subscribe is provided.

• NCBI RSS Feeds - Receive announcements about various NCBI services using an RSS (Real simple syndication) feed reader. RSS feeds are available for resources such as Bookshelf, HomoloGene, PubMed Central, PubMed New and Noteworthy, Probe Database, and UniGene. Follow the link to the NCBI RSS Feeds page to see a complete list of available topics. Additional information about RSS is provided in a short series of FAQs.

General Information (sample record, release notes, GenBank divisions, statistics),   Submissions (general, special categories, other data types),   International Collaboration,   FTP GenBank

• General information about submitting nucleotide sequence data to GenBank, receiving accession numbers, and making updates to records. Special types of submissions to GenBank, such as genomes, alignments, ESTs, GSSs, HTGs, STSs, and WGS are discussed below.

In addition to GenBank, there are other databases at NCBI to which a variety of data types can be submitted (third party annotations (TPA), variation, expression, MHC data, SKY/M-FISH/CGH data, traces).

• BankIt - WWW submission tool for one or few submissions, designed to make the submission process quick and easy.  (BankIt also automatically uses VecScreen to identify segments of nucleic acid sequence which may be of vector, adapter, or linker origin to combat the problem of vector contamination in GenBank.)

• Sequin - submission software program for one or many submissions, long sequences, complete genomes, alignments, population/phylogenetic/mutation studies. Can be used as a stand-alone application or in a TCP/IP-based "network aware" mode, with links to other NCBI resources and software such as Entrez.  (Use VecScreen prior to submission).  To receive announcements about updates to the Sequin submission software, see the NCBI Announcements Email Lists page.

• Submission of complete genomes and other large sequence records - Recent enhancements to Sequin make it convenient for genome sequencing centers to annotate their records with Sequin and submit the resulting ASN.1 file to GenBank. After the Sequin files are prepared, large genomes should be submitted by ftp; write to genomes@ncbi.nlm.nih.gov to obtain an ftp account. Smaller records less than 350 kb can be sent by email to gb-sub@ncbi.nlm.nih.gov.
  
  More information about submitting genomes and other large sequence records is provided on the following pages: GenBank submissions, Sequin, tabular layout for submitting annotated features, bacterial genome submission guidelines.
  
  In addition, sequencing centers can register a sequencing project with NCBI prior to the submission of any data. This can be done through a Genome project submission form. For each registered project, NCBI will create a sequencing project page that describes the project, links out to genome-specific reosurces, and provides a focal point for the addition of links to NCBI resources such as Map Viewer and genomic BLAST. Projects can be listed publicly or remain unlisted, and sequences may be held until publication (the default), released immediately, or made available for BLAST searches only. The form can also be used to set up an FTP site for the upload of data to NCBI, or to specify a URL to be used by NCBI for download of project or sequence data. (See Fall 2003/Winter 2004 issue of NCBI News for more information.)

• Alignments - submission of aligned sequences from population, phylogenetic, or mutation studies. Several sections of the Sequin Help Documentation also include information on how to submit alignments, such as Submission Type, FAST A+GA P Format for Aligned Nucleotide Sequences, PHYLIP Format for Aligned Nucleotide Sequences, NEXUS Format for Aligned Nucleotide Sequences, Source Modifiers for PHYLIP and NEXUS, Importin g Aligned Sets of Segmented Sequences. Check the Sequin help documentation for other relevant sections. (See Fall 2003/Winter 2004 issue of NCBI News for an example in the "Submissions Corner".)

• ESTs - expressed sequence tags; short, single pass read cDNA (mRNA) sequences. Also includes cDNA sequences from differential display experiments and RACE experiments.

• GSSs - genome survey sequences; short, single pass read genomic sequences, exon trapped sequences, cosmid/BAC/YAC ends, others.

• HTGs - high throughput genome sequences from large scale genome sequencing centers; unfinished (phase 0, 1, 2) and finished (phase 3) sequences. (Note that contigs assembled from draft and finished human HTG sequences are accessible from the Map Viewer, described below.)

• STSs - sequence tagged sites; short sequences that are operationally unique in the genome, used to generate mapping reagents.

• WGS - data from Whole Genome Shotgun (WGS) sequencing projects can be submitted to GenBank. The data can contain annotations and an entire project is updated as sequencing progresses. WGS submissions are given accession numbers in the format of four letters followed by eight digits, e.g., XXXX00000000. The four letters are a stable project_ID, which does not change as the project is updated. The first two digits represent the version number, which corresponds to a particular project update. The last six digits represent an individual contig within the WGS project. For example, if a project's assigned accession number is XXXX00000000, then that project's first assembly version would be XXXX01000000, and the first contig of that version would be XXXX01000001. (more...)
  The nucleotide data from WGS projects go into the appropriate organismal GenBank Divisions and the BLAST wgs database. The protein translations of annotated coding sequences go into the BLAST protein nr database. In addition, quality data from many WGS projects are submitted to the Trace Archive (described in the ResourceGuide section on Nucleotide Sequence Databases).

• Third Party Annotations (TPA) - a database of experimentally supported annotations on assemblies of sequences already present in DDBJ/EMBL/GenBank. Whereas DDBJ/EMBL/GenBank contains primary sequence data and corresponding annotations submitted by the laboratories that did the sequencing, the TPA database contains third-party assemblies of primary data with experimentally supported annotation that has been published in a peer-reviewed scientific journal. Details about how to submit data, as well as examples of what can and cannot be submitted to TPA, are provided on the TPA home page. Additional information about the TPA database is provided below.

• Genetic Variation - in humans and other organisms can be submitted to the NCBI Database of Single Nucleotide Polymorphisms (dbSNP).  Although dbSNP is a separate database from GenBank, as noted above, SNP records include cross-references to GenBank records.  (submission instructions)  Additional information about dbSNP is below.

• Gene Expression - data can be submitted to Gene Expression Omnibus (GEO)  (submission instructions).  Additional information about GEO is below.

• Major Histocompatibility Complex (MHC) - DNA sequence and clinical data can be submitted to dbMHC.   A brief description of dbMHC is provided in the Molecular Databases/Nucleotide Sequences section of this guide, and additional details are available in the NCBI Handbook.

• Spectral Karyotyping (SKY), Multiplex Fluorescence In Situ Hybridization (M-FISH), and Comparative Genomic Hybridization (CGH) - data can be submitted to the NCI and NCBI SKY/M-FISH & CGH Database  (submission instructions)  Additional information about the NCI and NCBI SKY/M-FISH & CGH Database is below.

• Trace Data - can be submitted to the Trace Archive, a repository of the raw sequence traces generated by large sequencing projects.  (submission instructions)  Additional information about the Trace Archive is below.

Nucleotide Sequences,   Protein Sequences,   Structures,   Genes,   Expression,   Taxonomy

Consensus CoDing Sequence (CCDS) Database - The CCDS project is a collaborative effort to identify a core set of human protein coding regions that are consistently annotated and of high quality. The long term goal is to support convergence towards a standard set of gene annotations on the human genome. The collaborators include the National Center for Biotechnology Information (NCBI, Map Viewer), European Bioinformatics Institute (EBI, Ensembl), University of California, Santa Cruz (UCSC, Genome Browser), and Wellcome Trust Sanger Institute (WTSI, Vega). They identify the position of protein-coding regions of genes that are (1) annotated consistently on the human genome by all of the participating centers and (2) supported by transcript evidence, use of canonical splice sites, and other quality assurance measures. Additional information about the curation, process flow, and quality testing is available on the CCDS web site.

Note:  Although TPA records are derived from DDBJ/EMBL/GenBank, TPA is actually a separate database. Therefore, TPA records are not present in the GenBank FTP files, but will be available in separate FTP files.

The TPA database uses an accession format similar to GenBank records (e.g., two letters followed by six digits) and is organized into similar divisions. (A list of GenBank divisions is given in the GenBank Sample Record. Some divisions, such as EST, GSS, HTG and are present in GenBank but will not be present in TPA.)

TPA records can be easily recognized because the definition lines begin with the the letters "TPA", and they contain "Third Party Annotation; TPA" in the Keywords field. This is illustrated in a sample TPA record, BK000627.

TPA records can be retrieved from Entrez Nucleotides (described above). To only see data from TPA, use the "Index" mode to select "tpa" from the Properties search field, or simply add the command AND tpa[prop] to your query.

Details about how to submit data, as well as examples of what can and cannot be submitted to TPA, are provided on the TPA home page. An announcement and additional information about the TPA database is provided in section 1.4.5, "Third-Party Annotation and Consensus Sequences (TPA)" of the GenBank 133.0 release notes.

Assembly Archive - links the raw sequence information found in the Trace Archive with assembly information found in publicly available sequence repositories (GenBank/EMBL/DDBJ). The Assembly Viewer allows a user to see the multiple sequence alignments as well as the actual sequence chromatogram.

• Resources in the Genomes and Maps section contain annotations for the proteins encoded by a variety of genomes. Examples of the genomes available include:   >1000 organisms in Entrez Genome, human, mouse, rat, zebrafish, Drosophila, nematode, plant genomes, yeast, malaria, microbial genomes, viruses, viroids, plasmids, eukaryotic organelles. The proteomes of human, mouse, rat, and a growing number of other eukaryotes are also shown as annotations on the genomes of those organisms in Map Viewer (described in the Genomes and Maps section). MapViewer can display the data graphically or in tabular format, and also provides links to corresponding data on the FTP site.

• Entrez Genome - provides ProtTable and TaxTable for various organisms. The ProtTable provides a summary of protein coding regions in a genome, and provides links to the corresponding nucleotide and protein sequences in FASTA format. The TaxTable, also referred to as the "distribution of BLAST protein homologs by taxa," summarizes the results of BLAST analyses done for the proteins, and displays the relationship of the organism to others through a color-coded graphical summary. (Additional information about Entrez Genome is provided below.)

• FTP Genome Proteins - download an *.faa file (FASTA formatted amino acid sequences) and *ptt file (protein table) for various organisms from the genbank/genomes directory of the ftp site; see readme file for more information. Protein tables can also be viewed in Entrez Genome, as noted above.

• PubChem Substance - Primary data NCBI obtains from the various public depositories. The PubChem Substance database contains approximately 13 million records as of October 2006, provided by various sources, DTP/NCI, NIAID, ChemIDplus, NIST, NIST webbook, MOLI/NCI, ChemBank, MMDB, KEGG, and more. Substance information includes chemical structures, synonyms, registration IDs, descriptions, related urls, and database cross-reference links to PubMed, protein 3D structures, and biological screening results.

• PubChem Compound - A database made by NCBI and derived from PCSubstance. It is a non-redundant view of the chemically validated substances in PubChem Substance. There is one PubChem Compound record for each unique substance, and for each unique substance component. There can be multiple PubChem Substance records associated with one PubChem Compound record. PubChem Compound contains all standardized structures, mixture components, and precalculated structure neighboring links. Compound information includes structure, compound property information (molecular weight, formula, xLogP, count of the rotatable bonds, H bond donor, H bond acceptor, etc.), and structure description (SMILES, IUPAC name, INCHI).

• PubChem BioAssay - The assay database consists of deposited bioactivity data and descriptions of bioactivity assays used for screening of the chemical substances contained in PubChem Substance, including descriptions of the conditions and the readouts (bioactivity levels) specific to the screening procedure. The assay database includes DTP/NCI's 710 million lines of in vitro and in vivo data covering from cancer, HIV, to many other fields.

• Cn3D - "See in 3-D," a structure and sequence alignment viewer for NCBI databases. It allows viewing of 3-D structures and sequence-structure or structure-structure alignments. Cn3D can work as a helper application to your browser, or as a client-server application that retrieves structure records from MMDB (described above) directly over the internet. The Cn3D home page provides access to information on how to install the program, a tutorial to get started, and a comprehensive help document.

• CD-Search - The Conserved Domain Search Service (CD-Search) can be used to identify the conserved domains present in a protein sequence. CD-Search uses RPS-BLAST (described above) to compare a query sequence against position-specific score matrices that have been prepared from conserved domain alignments present in the Conserved Domain Database (CDD) (described above). Hits can be displayed as a pairwise alignment of the query sequence with a representative domain sequence, or as a multiple alignment. Alignments are also mapped to known 3-dimensional structures, and can be displayed using Cn3D (described above). In the Cn3D display, residues in sequence alignments are variously colored, based on their degree of conservation.

• VAST - Vector Alignment Search Tool - a computer algorithm developed at NCBI and used to identify similar protein 3-dimensional structures. The "structure neighbors" for every structure in MMDB are pre-computed and accessible via links on the MMDB Structure Summary pages. These neighbors can be used to identify distant homologs that cannot be recognized by sequence comparison alone.

• VAST Search - structure-structure similarity search service. Compares 3D coordinates of a newly determined protein structure to those in the MMDB/PDB database. VAST Search computes a list of structure neighbors that you may browse interactively, viewing superpositions and alignments by molecular graphics.

GeneRIF - Gene References into Function (GeneRIFs) provide a simple mechanism to allow scientists to add to the functional annotation of loci described in Entrez Gene. They appear as annotated bibliographies in Entrez Gene records, and consist of brief statements on gene function with links to the corresponding PubMed records (example: human MLH1). The GeneRIF help page describes the simple steps needed to submit information. GeneRIFs are also added to the Entrez Gene records by the MEDLINE Indexing Staff of the National Library of Medicine. GeneRIFs are currently available for a subset of organisms in Entrez Gene, and will be provided for the loci of other organisms as the development of Entrez Gene continues.

LocusLink - LocusLink was discontinued as of March 1, 2005. It provided a foundation for what is now Entrez Gene and was described in several articles ( Pruitt KD, Maglott DR (2001), Pruitt KD, Katz KS, Sicotte H, Maglott DR (2000)). It contained data for a number of species such as human, mouse, rat, zebrafish, nematode, fruit fly, cow, sea urchin, African clawed frog, HIV-1, and a few other model and commonly studied organisms. Data for these organisms (and from the ongoing collaboration among the groups listed above) are now available in the Entrez Gene database (described above), which is the successor to LocusLink. The major differences between LocusLink and Entrez Gene are scope of data and search interface. Entrez Gene contains data from all organisms with RefSeq genome records. (RefSeq is described in the Molecular Databases/Nucleotide Sequences section of this guide). Entrez Gene also uses the Entrez search system, and therefore offers the helpful functions such as Preview/Index, History, and LinkOut that are available for other Entrez databases. The Entrez Gene help document includes numerous tips for previous users of LocusLink.

• SAGEmap - Serial Analysis of Gene Expression, or SAGE, is an experimental technique designed to quantitatively measure gene expression. SAGEmap is an online tool to compare computed gene expression profiles between SAGE libraries generated by the Cancer Genome Anatomy Project (CGAP, described under human genome/cancer research) and submitted by others through the Gene Expression Omnibus (GEO, described above). SAGEmap also includes a comprehensive analysis of SAGE tags in human GenBank records, in which a UniGene identifier is assigned to each human sequence that contains a SAGE tag. Data can be retrieved by tag, by sequence, by UniGene cluster ID and by library name. When retrieving data by sequence or UniGene cluster ID, follow a SAGE tag's hotlink to find out its expression level in different SAGE libraries, and how it is represented in the rest of the sequences in GenBank. Retrieving data by library name takes one to GEO, where all SAGEmap data has been stored by library. Analytical tools include xProfiler, which compares gene expression between SAGE libraries of your choice as well as uploaded data. More information about the additional analytical capabilities of the SAGEmap resource is provided in the tools/gene expression section of this file.

• CGAP - Cancer Genome Anatomy Project - interdisciplinary program to identify the human genes expressed in different cancerous states, based on cDNA (EST) libraries, and to determine the molecular profiles of normal, precancerous, and malignant cells. Collaboration among the National Cancer Institute, the NCBI, and numerous research labs. Additional information about CGAP is provided in the tools/gene expression section of this file. Related resources are described in the human genome/cancer research section.

• UniGene DDD - Digital Differential Display - an online tool to compare computed gene expression profiles between selected cDNA libraries. Using a statistical test, genes whose expression levels differ significantly from one tissue to the next are identified and shown to the user. Additional information about UniGene is in the molecular databases/genes section.

• Journals Database - allows you to lookup journals that are cited in any of the Entrez databases, including PubMed. Journals can be searched using the journal title, MEDLINE or ISO abbreviation, ISSN, or the NLM Catalog ID.

• MeSH - The Medical Subject Headings (MeSH) database is NLM's controlled vocabulary used for indexing articles for MEDLINE/PubMed. MeSH terminology provides a consistent way to retrieve information that may use different terminology for the same concepts.

• Citation Matcher - allows you to find the PubMed ID of any article in the PubMed database, given its bibliographic information (journal, volume, page, etc.).
• Citation Matcher for single articles
• Batch Citation Matcher for many articles

Information about submitting genome data from complete genomes is provided in the Resource Guide section on Submission of complete genomes. After data from complete genomes are submitted, they are made available in Entrez Genome (as complete genomes or chromosomes) and Entrez Nucleotide (as chromosome or genome fragments such as contigs). Entrez Nucleotide also provides access to the records for complete genomes/chromosomes, but the default view of those records is the Nucleotide database is GenBank format, whereas the default view in Entrez Genome is a graphical overview. A companion database, Entrez Genome Project, is described below.