GenBank: The Nucleotide Sequence Database

1. GenBank: The Nucleotide Sequence Database nE+OBdl  
Ilene Mizrachi 3x2*K_A5:Q  
Created: October 9, 2002 V;$ME4B\{  
Updated: August 22, 2007 u'}SaX]0  
Summary v: 0.  
The GenBank sequence database is an annotated collection of all publicly available nucleotide P+00wbx0  
sequences and their protein translations. This database is produced at National Center for L h"K"Uv  
Biotechnology Information (NCBI) as part of an international collaboration with the European Molecular u2crL5^z2)  
Biology Laboratory (EMBL) Data Library from the European Bioinformatics Institute (EBI) and the DNA )`5kfj  
Data Bank of Japan (DDBJ). GenBank and its collaborators receive sequences produced in mZLrU<)Y  
laboratories throughout the world from more than 100,000 distinct organisms. GenBank continues to --*Jv"/0  
grow at an exponential rate, doubling every 10 months. Release 134, produced in February 2003, _kR);\V.8  
contained over 29.3 billion nucleotide bases in more than 23.0 million sequences. GenBank is built .9X
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by direct submissions from individual laboratories, as well as from bulk submissions from large-scale a?#v,4t^  
sequencing centers. !.>TF

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Direct submissions are made to GenBank using BankIt [http://www.ncbi.nlm.nih.gov/BankIt/], P YWp2V/  
which is a Web-based form, or the stand-alone submission program, Sequin [http:// \%Wu`SlDp9  
www.ncbi.nlm.nih.gov/Sequin/index.html]. Upon receipt of a sequence submission, the GenBank staff R7YLI1ov  
assigns an Accession number to the sequence and performs quality assurance checks. The 3(D!]ku~
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submissions are then released to the public database, where the entries are retrievable by Entrez or rXR=fj= 2  
downloadable by FTP. Bulk submissions of Expressed Sequence Tag (EST), Sequence Tagged Site ,m<t/@^]  
(STS), Genome Survey Sequence (GSS), and High-Throughput Genome Sequence (HTGS) data are yu8xTh$:  
most often submitted by large-scale sequencing centers. The GenBank direct submissions group also V2-fJ!  
processes complete microbial genome sequences. LRNgpjE}  
History *7MTq_K(An  
Initially, GenBank was built and maintained at Los Alamos National Laboratory (LANL). In the early Wp!#OY1?
 
1990s, this responsibility was awarded to NCBI through congressional mandate. NCBI undertook ux-puG  
the task of scanning the literature for sequences and manually typing the sequences into the data- w
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base. Staff then added annotation to these records, based upon information in the published article. h>>KH*dQ  
Scanning sequences from the literature and placing them into GenBank is now a rare occurrence. (.6~t<DRv  
Nearly all of the sequences are now deposited directly by the labs that generate the sequences. |8,|>EyqK  
This is attributable to, in part, a requirement by most journal publishers that nucleotide sequences tNsiokOm  
are first deposited into publicly available databases (DDBJ/EMBL/GenBank) so that the Accession '~-JR>  
number can be cited and the sequence can be retrieved when the article is published. NCBI began p9c`rl_N  
1-1 F$[1KjS  
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NCBI Handbook GenBank 3Yu1ZuIR  
accepting direct submissions to GenBank in 1993 and received data from LANL until 1996. Cur- _^{!`*S  
rently, NCBI receives and processes about 20,000 direct submission sequences per month, in =3KK /[2M  
addition to the approximately 200,000 bulk submissions that are processed automatically. ;IklS*p]  
International Collaboration <HReh>)[  
In the mid-1990s, the GenBank database became part of the International Nucleotide Sequence +n#(QOz  
Database Collaboration with the EMBL database (European Bioinformatics Institute [http:// IB~`Ht8 b  
www.ebi.ac.uk/], Hinxton, United Kingdom) and the Genome Sequence Database (GSDB; LANL, >eF4YZ"  
Los Alamos, NM). Subsequently, the GSDB was removed from the Collaboration (by the National v]`}T/n  
Center for Genome Resources, Santa Fe, NM), and DDBJ [http://www.ddbj.nig.ac.jp/] (Mishima, @y3u'Y,B  
Japan) joined the group. Each database has its own set of submission and retrieval tools, but the  U~%V;*|4  
three databases exchange data daily so that all three databases should contain the same set of T)QZ9a  
sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical JY$B%R4;]  
issues, and an international advisory board meets with the database staff to provide additional Yc5{M*w  
guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting ;=.i+  
data at the three sites. 6O|B'?]Pf  
The Collaboration created a Feature Table Definition [http://www.ncbi.nlm.nih.gov/collab/FT/ d=?Kk4Ag  
index.html] that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. aD5jy  
The purpose of this document is to standardize annotation across the databases. The presentation 2|J>e(&akY  
and format of the data are different in the three databases, however, the underlying biological infor- "rnZ<A}
  
mation is the same. {Pi+V uLE  
Confidentiality of Data ;'^5$q  
When scientists submit data to GenBank, they have the opportunity to keep their data confidential ?fO 2&)r  
for a specified period of time. This helps to allay concerns that the availability of their data in Gen- G$hH~{Y$  
Bank before publication may compromise their work. When the article containing the citation of the ' KX'{Gy  
sequence or its Accession number is published, the sequence record is released. The database x2@Q5|a  
staff request that submitters notify GenBank of the date of publication so that the sequence can be M$|r8%z1  
released without delay. The request to release should be sent to gb-admin@ncbi.nlm.nih.gov. ho5mH{"OV  
Direct Submissions axf4N@  
The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence DA> _9o/l  
with annotations. The annotations are meant to provide an adequate representation of the biological Mi|PhDXMh  
information in the record. The GenBank Feature Table Definition [http://www.ncbi.nlm.nih.gov/col- N$Pi4  
lab/FT/index.html] describes the various features and subsequent qualifiers agreed upon by the B.zRDB}i=  
International Nucleotide Sequence Database Collaboration. I/whpOg  
Currently, only nucleotide sequences are accepted for direct submission to GenBank. These >U.)?>G/dt  
include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or P!;%DI!<b  
multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a QG~4<zy  
1-2 H ;#3 S<  
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NCBI Handbook GenBank fgmu*\x<  
protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the Equj[yw%@  
CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession num- MMyVm"w  
ber (/protein_id) is assigned to the translation product, which will subsequently be added to the Mq!vu!  
protein databases. W u4` 3  
Multiple sequences can be submitted together. Such batch submissions of non-related sequen- 2` D1 cX  
ces may be processed together but will be displayed in Entrez (Chapter 15) as single records. Im7t8XCG  
Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several Gp0B^^H$  
sequences are biologically related. Such sequences are classified as environmental sample sets,  AKKp-I5  
population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set --(e(tvf  
is assigned its own Accession number and can be viewed independently in Entrez. However, with oCl $ 0x  
the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus FXpI-?#E<  
allowing scientists to view the relationship between the sequences. r8o9C  
What defines a set? Environmental sample, population, phylogenetic, and mutation sets all '}\#bMeObg  
contain a group of sequences that spans the same gene or region of the genome. Environmental KW3Dr`A  
samples are derived from a group of unclassified or unknown organisms. A population set contains W%3<"'eP  
sequences from different isolates of the same organism. A phylogenetic set contains sequences 9VEx0mkdd  
from different organisms that are used to determine the phylogenetic relationship between them. 7Wd}H Z  
Sequencing multiple mutations within a single gene gives rise to a mutation set. 0|1)cO}Dy  
All sets, except segmented sets, may contain an alignment of the sequences within them and i,[
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might include external sequences already present in the database. In fact, the submitter can begin #:^aE|s  
with an existing alignment to create a submission to the database using the Sequin submission tool. |.OXe!uU41  
Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Con- -i,=sZXB  
tiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez. .3yoDab  
Segmented sets are a collection of noncontiguous sequences that cover a specified genetic aan)yP  
region. The most common example is a set of genomic sequences containing exons from a single k9V#=,K0  
gene where part or all of the intervening regions have not been sequenced. Each member record 8'niew 5d  
within the set contains the appropriate annotation, exon features in this case. However, the mRNA b7t hu5  
and CDS will be annotated as joined features across the individual records. Segmented sets them- >I9w|zFA  
selves can be part of an environmental sample, population, phylogenetic, or mutation set.