GenBank: The Nucleotide Sequence Database

1. GenBank: The Nucleotide Sequence Database "M,H
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Ilene Mizrachi uTy00`1  
Created: October 9, 2002 #=Whh 9-d  
Updated: August 22, 2007 semTAoqH  
Summary m5 W':vM  
The GenBank sequence database is an annotated collection of all publicly available nucleotide :aD_>,n  
sequences and their protein translations. This database is produced at National Center for p1IN%*IV+o  
Biotechnology Information (NCBI) as part of an international collaboration with the European Molecular ]@l;;Sp  
Biology Laboratory (EMBL) Data Library from the European Bioinformatics Institute (EBI) and the DNA G}nj 71=H  
Data Bank of Japan (DDBJ). GenBank and its collaborators receive sequences produced in qI[AsM+  
laboratories throughout the world from more than 100,000 distinct organisms. GenBank continues to /5Yl, P  
grow at an exponential rate, doubling every 10 months. Release 134, produced in February 2003, ]hbrzvo  
contained over 29.3 billion nucleotide bases in more than 23.0 million sequences. GenBank is built }RQHsS  
by direct submissions from individual laboratories, as well as from bulk submissions from large-scale _iu^VK,}  
sequencing centers. f2ck=3  
Direct submissions are made to GenBank using BankIt [http://www.ncbi.nlm.nih.gov/BankIt/], *(sv5c!0M8  
which is a Web-based form, or the stand-alone submission program, Sequin [http:// p<B*)1Tj0  
www.ncbi.nlm.nih.gov/Sequin/index.html]. Upon receipt of a sequence submission, the GenBank staff m4R:K jN*  
assigns an Accession number to the sequence and performs quality assurance checks. The c7R6.T  
submissions are then released to the public database, where the entries are retrievable by Entrez or ] B>.}  
downloadable by FTP. Bulk submissions of Expressed Sequence Tag (EST), Sequence Tagged Site Gw
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(STS), Genome Survey Sequence (GSS), and High-Throughput Genome Sequence (HTGS) data are \M*c3\&~,e  
most often submitted by large-scale sequencing centers. The GenBank direct submissions group also Kw`}hSE>o  
processes complete microbial genome sequences. Qn@[{%),4  
History WH.3  
Initially, GenBank was built and maintained at Los Alamos National Laboratory (LANL). In the early |gfG\fL3V  
1990s, this responsibility was awarded to NCBI through congressional mandate. NCBI undertook -hGLGF??  
the task of scanning the literature for sequences and manually typing the sequences into the data-  Uf|@h  
base. Staff then added annotation to these records, based upon information in the published article. VzWH9%w  
Scanning sequences from the literature and placing them into GenBank is now a rare occurrence. 9o
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Nearly all of the sequences are now deposited directly by the labs that generate the sequences. f
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This is attributable to, in part, a requirement by most journal publishers that nucleotide sequences t1!>EI`  
are first deposited into publicly available databases (DDBJ/EMBL/GenBank) so that the Accession J #;|P -pt  
number can be cited and the sequence can be retrieved when the article is published. NCBI began Hr*xAx  
1-1 @ b}-<~  
 >Xxi2Vy  
NCBI Handbook GenBank :VX2&*  
accepting direct submissions to GenBank in 1993 and received data from LANL until 1996. Cur- 3O|2Z~>3  
rently, NCBI receives and processes about 20,000 direct submission sequences per month, in p,3}A(>  
addition to the approximately 200,000 bulk submissions that are processed automatically. 9{-H/YS\_s  
International Collaboration ].@8/. rg  
In the mid-1990s, the GenBank database became part of the International Nucleotide Sequence <}}u'5;^?x  
Database Collaboration with the EMBL database (European Bioinformatics Institute [http:// 4UMOC_  
www.ebi.ac.uk/], Hinxton, United Kingdom) and the Genome Sequence Database (GSDB; LANL, m-Qy6"eW  
Los Alamos, NM). Subsequently, the GSDB was removed from the Collaboration (by the National zOYG`:/'  
Center for Genome Resources, Santa Fe, NM), and DDBJ [http://www.ddbj.nig.ac.jp/] (Mishima, s6Il3Kf  
Japan) joined the group. Each database has its own set of submission and retrieval tools, but the )c<[@::i  
three databases exchange data daily so that all three databases should contain the same set of MwaRwk ;  
sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical 3.h0  
issues, and an international advisory board meets with the database staff to provide additional {O4&HW%  
guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting !^Q4ZL,-  
data at the three sites. u&e?3qKX(  
The Collaboration created a Feature Table Definition [http://www.ncbi.nlm.nih.gov/collab/FT/ 5e^z]j1Yv  
index.html] that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. 7s0pH+  
The purpose of this document is to standardize annotation across the databases. The presentation Q5*"t*L!N  
and format of the data are different in the three databases, however, the underlying biological infor- ;b
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mation is the same. `_
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Confidentiality of Data eRg;)[#0>$  
When scientists submit data to GenBank, they have the opportunity to keep their data confidential ob9=/ R?i  
for a specified period of time. This helps to allay concerns that the availability of their data in Gen- =h/61Bl3  
Bank before publication may compromise their work. When the article containing the citation of the n]3Z~HoZ  
sequence or its Accession number is published, the sequence record is released. The database -~ Dn^B1^  
staff request that submitters notify GenBank of the date of publication so that the sequence can be g+-^6UG  
released without delay. The request to release should be sent to gb-admin@ncbi.nlm.nih.gov. 5IbCE.>iU  
Direct Submissions Sre:l'
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The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence ogoEtKi  
with annotations. The annotations are meant to provide an adequate representation of the biological xj Jo WB  
information in the record. The GenBank Feature Table Definition [http://www.ncbi.nlm.nih.gov/col- J5}?<Dd:  
lab/FT/index.html] describes the various features and subsequent qualifiers agreed upon by the %:7/ym[  
International Nucleotide Sequence Database Collaboration. h3Nbgxa.  
Currently, only nucleotide sequences are accepted for direct submission to GenBank. These YOtzja]~  
include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or 9!6u Yf+  
multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a g ~%IA.$c  
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NCBI Handbook GenBank [!4V_yOb  
protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the y.a)M?3  
CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession num- jK2gc^"t  
ber (/protein_id) is assigned to the translation product, which will subsequently be added to the Jjh=zxR>  
protein databases. }U**)"  
Multiple sequences can be submitted together. Such batch submissions of non-related sequen- %/R[cj8  
ces may be processed together but will be displayed in Entrez (Chapter 15) as single records. u89Q2\z~"M  
Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several 'i 8`LPQ  
sequences are biologically related. Such sequences are classified as environmental sample sets, +l<;?yk:;  
population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set S0;s 7X#c  
is assigned its own Accession number and can be viewed independently in Entrez. However, with Nb\B*=4AR  
the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus f5'vjWJ30  
allowing scientists to view the relationship between the sequences. c\rP"y|S};  
What defines a set? Environmental sample, population, phylogenetic, and mutation sets all 3 &B- w  
contain a group of sequences that spans the same gene or region of the genome. Environmental isz-MP$:K5  
samples are derived from a group of unclassified or unknown organisms. A population set contains YyC$\HH6   
sequences from different isolates of the same organism. A phylogenetic set contains sequences K^%ONultv  
from different organisms that are used to determine the phylogenetic relationship between them. J?f7!F:8  
Sequencing multiple mutations within a single gene gives rise to a mutation set. I%CrsEo  
All sets, except segmented sets, may contain an alignment of the sequences within them and GsIqUM#R  
might include external sequences already present in the database. In fact, the submitter can begin H)5"<=]  
with an existing alignment to create a submission to the database using the Sequin submission tool. *Q;?p
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Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Con- l2kUa'O-  
tiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez. [vxHsY3z  
Segmented sets are a collection of noncontiguous sequences that cover a specified genetic ,jeC7-tX  
region. The most common example is a set of genomic sequences containing exons from a single Oki{)Ssy  
gene where part or all of the intervening regions have not been sequenced. Each member record @Z Dd(xB&  
within the set contains the appropriate annotation, exon features in this case. However, the mRNA I\|.WrMNi  
and CDS will be annotated as joined features across the individual records. Segmented sets them- ^_uCSA'X  
selves can be part of an environmental sample, population, phylogenetic, or mutation set.