GenBank: The Nucleotide Sequence Database

1. GenBank: The Nucleotide Sequence Database N.?)s.D(  
Ilene Mizrachi u9D#5NvGs  
Created: October 9, 2002 a G\  
Updated: August 22, 2007 X*e<g=  
Summary 0 ![  
The GenBank sequence database is an annotated collection of all publicly available nucleotide @Q%<~b[y  
sequences and their protein translations. This database is produced at National Center for .{4U]a;[  
Biotechnology Information (NCBI) as part of an international collaboration with the European Molecular VTJxVYE  
Biology Laboratory (EMBL) Data Library from the European Bioinformatics Institute (EBI) and the DNA
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Data Bank of Japan (DDBJ). GenBank and its collaborators receive sequences produced in PEPf=sm  
laboratories throughout the world from more than 100,000 distinct organisms. GenBank continues to #GOL%2X  
grow at an exponential rate, doubling every 10 months. Release 134, produced in February 2003, OtZc;
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contained over 29.3 billion nucleotide bases in more than 23.0 million sequences. GenBank is built rvp#[RAaS}  
by direct submissions from individual laboratories, as well as from bulk submissions from large-scale C
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sequencing centers. eWWfUNBSLX  
Direct submissions are made to GenBank using BankIt [http://www.ncbi.nlm.nih.gov/BankIt/], lC'U3Q&  
which is a Web-based form, or the stand-alone submission program, Sequin [http:// D ]G=sYt  
www.ncbi.nlm.nih.gov/Sequin/index.html]. Upon receipt of a sequence submission, the GenBank staff Sq[LwJ  
assigns an Accession number to the sequence and performs quality assurance checks. The Xsd+5="{N  
submissions are then released to the public database, where the entries are retrievable by Entrez or T[ltOQw?Y  
downloadable by FTP. Bulk submissions of Expressed Sequence Tag (EST), Sequence Tagged Site u_jhmKr~  
(STS), Genome Survey Sequence (GSS), and High-Throughput Genome Sequence (HTGS) data are aM|;3j1p  
most often submitted by large-scale sequencing centers. The GenBank direct submissions group also R _2T"  
processes complete microbial genome sequences. nWFU8u%  
History 9qI#vHA  
Initially, GenBank was built and maintained at Los Alamos National Laboratory (LANL). In the early T':} p2}w+  
1990s, this responsibility was awarded to NCBI through congressional mandate. NCBI undertook #TPS?+(  
the task of scanning the literature for sequences and manually typing the sequences into the data- `%Dz 8Z  
base. Staff then added annotation to these records, based upon information in the published article. A^vvw~!d
 
Scanning sequences from the literature and placing them into GenBank is now a rare occurrence. A8T8+M:  
Nearly all of the sequences are now deposited directly by the labs that generate the sequences. )6*)u/x:  
This is attributable to, in part, a requirement by most journal publishers that nucleotide sequences UZx8ozv'  
are first deposited into publicly available databases (DDBJ/EMBL/GenBank) so that the Accession v/x~L$[  
number can be cited and the sequence can be retrieved when the article is published. NCBI began .> 5[;  
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NCBI Handbook GenBank %gEgpJd  
accepting direct submissions to GenBank in 1993 and received data from LANL until 1996. Cur- JVR,Py:%G  
rently, NCBI receives and processes about 20,000 direct submission sequences per month, in U?=-V8#M|  
addition to the approximately 200,000 bulk submissions that are processed automatically. Cq[<CPAS  
International Collaboration *9tRhRc  
In the mid-1990s, the GenBank database became part of the International Nucleotide Sequence s y>}2orj~  
Database Collaboration with the EMBL database (European Bioinformatics Institute [http:// ::sk)  
www.ebi.ac.uk/], Hinxton, United Kingdom) and the Genome Sequence Database (GSDB; LANL, <op|yh3Jkk  
Los Alamos, NM). Subsequently, the GSDB was removed from the Collaboration (by the National Kp>fOe'KW  
Center for Genome Resources, Santa Fe, NM), and DDBJ [http://www.ddbj.nig.ac.jp/] (Mishima, I R~szUY6  
Japan) joined the group. Each database has its own set of submission and retrieval tools, but the 4
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three databases exchange data daily so that all three databases should contain the same set of Yht |^ =a  
sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical 2?@Ozr2Uh  
issues, and an international advisory board meets with the database staff to provide additional n;e.N:p  
guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting g17 fge6%  
data at the three sites. s9,Z}]Th  
The Collaboration created a Feature Table Definition [http://www.ncbi.nlm.nih.gov/collab/FT/ eI1C0Uz1  
index.html] that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. h^'+y1
 
The purpose of this document is to standardize annotation across the databases. The presentation Q!{,^Qb  
and format of the data are different in the three databases, however, the underlying biological infor- yOO@v6jO)  
mation is the same. <&l@ ):a  
Confidentiality of Data rmeGk&*R8  
When scientists submit data to GenBank, they have the opportunity to keep their data confidential +NTC!/  
for a specified period of time. This helps to allay concerns that the availability of their data in Gen- 7M<co,"  
Bank before publication may compromise their work. When the article containing the citation of the ]h'*L`   
sequence or its Accession number is published, the sequence record is released. The database `5SQ4  
staff request that submitters notify GenBank of the date of publication so that the sequence can be G UK%RC8  
released without delay. The request to release should be sent to gb-admin@ncbi.nlm.nih.gov. t'[`"pp=  
Direct Submissions aSIoq}c(  
The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence cH6J:0>W  
with annotations. The annotations are meant to provide an adequate representation of the biological Bo0f`EC I  
information in the record. The GenBank Feature Table Definition [http://www.ncbi.nlm.nih.gov/col- A8 !&Y;d  
lab/FT/index.html] describes the various features and subsequent qualifiers agreed upon by the lJt?0;gn  
International Nucleotide Sequence Database Collaboration. Sb^o`~ Eh  
Currently, only nucleotide sequences are accepted for direct submission to GenBank. These |Q$Dj!!1P  
include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or O+t'E9Fa  
multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a h059DiH  
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NCBI Handbook GenBank \5fvD8>H  
protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the MH=Ld=i  
CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession num- yC7lR#N8j0  
ber (/protein_id) is assigned to the translation product, which will subsequently be added to the HqXS-TG  
protein databases. hfpis==  
Multiple sequences can be submitted together. Such batch submissions of non-related sequen- Esf\Bo
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ces may be processed together but will be displayed in Entrez (Chapter 15) as single records. Zou;o9Ww  
Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several ~YXkAS:  
sequences are biologically related. Such sequences are classified as environmental sample sets, ;&XC*R+  
population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set meZZQ:eSl  
is assigned its own Accession number and can be viewed independently in Entrez. However, with F!P,%JmI<  
the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus m}'!W`<  
allowing scientists to view the relationship between the sequences.
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What defines a set? Environmental sample, population, phylogenetic, and mutation sets all T}Wse{  
contain a group of sequences that spans the same gene or region of the genome. Environmental yeA]j[ #  
samples are derived from a group of unclassified or unknown organisms. A population set contains av~kF  
sequences from different isolates of the same organism. A phylogenetic set contains sequences <(l`zLf4p  
from different organisms that are used to determine the phylogenetic relationship between them. !*
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Sequencing multiple mutations within a single gene gives rise to a mutation set. <GSp%r  
All sets, except segmented sets, may contain an alignment of the sequences within them and );{7 6  
might include external sequences already present in the database. In fact, the submitter can begin '`j MNKn\  
with an existing alignment to create a submission to the database using the Sequin submission tool. sU/vXweky"  
Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Con- 1i;Cw/mr  
tiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez. nGxG!  
Segmented sets are a collection of noncontiguous sequences that cover a specified genetic GjbOc   
region. The most common example is a set of genomic sequences containing exons from a single -m$2"_  
gene where part or all of the intervening regions have not been sequenced. Each member record \zhCGDm1_  
within the set contains the appropriate annotation, exon features in this case. However, the mRNA f{h2>nEj\  
and CDS will be annotated as joined features across the individual records. Segmented sets them- )N O,G  
selves can be part of an environmental sample, population, phylogenetic, or mutation set.