GenBank: The Nucleotide Sequence Database

1. GenBank: The Nucleotide Sequence Database ]"6<"1)  
Ilene Mizrachi .YRSd  
Created: October 9, 2002 6 -}gqkR  
Updated: August 22, 2007 uX[

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Summary k~ue^^r}  
The GenBank sequence database is an annotated collection of all publicly available nucleotide qT4s*kq r  
sequences and their protein translations. This database is produced at National Center for .
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Biotechnology Information (NCBI) as part of an international collaboration with the European Molecular (Q+3aEUE  
Biology Laboratory (EMBL) Data Library from the European Bioinformatics Institute (EBI) and the DNA =Wa\yBj_;m  
Data Bank of Japan (DDBJ). GenBank and its collaborators receive sequences produced in 7SCI_8`  
laboratories throughout the world from more than 100,000 distinct organisms. GenBank continues to _?ZT[t<  
grow at an exponential rate, doubling every 10 months. Release 134, produced in February 2003, ,R+u%bmn#  
contained over 29.3 billion nucleotide bases in more than 23.0 million sequences. GenBank is built f] }F_]  
by direct submissions from individual laboratories, as well as from bulk submissions from large-scale [6|vx},N  
sequencing centers. #,56vVY  
Direct submissions are made to GenBank using BankIt [http://www.ncbi.nlm.nih.gov/BankIt/], 0bE_iu>f'  
which is a Web-based form, or the stand-alone submission program, Sequin [http:// nq=fSK(  
www.ncbi.nlm.nih.gov/Sequin/index.html]. Upon receipt of a sequence submission, the GenBank staff XvdhPOMy  
assigns an Accession number to the sequence and performs quality assurance checks. The X#yl8k_  
submissions are then released to the public database, where the entries are retrievable by Entrez or \<} nn?~n  
downloadable by FTP. Bulk submissions of Expressed Sequence Tag (EST), Sequence Tagged Site v6:DA#0  
(STS), Genome Survey Sequence (GSS), and High-Throughput Genome Sequence (HTGS) data are p P @#|T  
most often submitted by large-scale sequencing centers. The GenBank direct submissions group also r!S iR(  
processes complete microbial genome sequences. VA0TY/{ ]  
History ~#@EjQCq  
Initially, GenBank was built and maintained at Los Alamos National Laboratory (LANL). In the early PewLg<?,G4  
1990s, this responsibility was awarded to NCBI through congressional mandate. NCBI undertook ($wYawz  
the task of scanning the literature for sequences and manually typing the sequences into the data- zP9!fA  
base. Staff then added annotation to these records, based upon information in the published article. -AX3Rnv^!  
Scanning sequences from the literature and placing them into GenBank is now a rare occurrence. Fv 9Z'#t  
Nearly all of the sequences are now deposited directly by the labs that generate the sequences. ^?2txLv,6  
This is attributable to, in part, a requirement by most journal publishers that nucleotide sequences Hpt)(Nz:  
are first deposited into publicly available databases (DDBJ/EMBL/GenBank) so that the Accession eZ cm3=WV|  
number can be cited and the sequence can be retrieved when the article is published. NCBI began NQG"}=KA  
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NCBI Handbook GenBank Y%faf.$/9  
accepting direct submissions to GenBank in 1993 and received data from LANL until 1996. Cur- EY>A(   
rently, NCBI receives and processes about 20,000 direct submission sequences per month, in `&_qK~&/X  
addition to the approximately 200,000 bulk submissions that are processed automatically. Bg`b*(Q  
International Collaboration (:\hor%  
In the mid-1990s, the GenBank database became part of the International Nucleotide Sequence \;3r  
Database Collaboration with the EMBL database (European Bioinformatics Institute [http:// h2q]!01XP  
www.ebi.ac.uk/], Hinxton, United Kingdom) and the Genome Sequence Database (GSDB; LANL, %;<FfS  
Los Alamos, NM). Subsequently, the GSDB was removed from the Collaboration (by the National g5E]o)  
Center for Genome Resources, Santa Fe, NM), and DDBJ [http://www.ddbj.nig.ac.jp/] (Mishima, 3EyN"Lvp{o  
Japan) joined the group. Each database has its own set of submission and retrieval tools, but the oVu>jO:.  
three databases exchange data daily so that all three databases should contain the same set of <ESAoY"RPN  
sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical iJYr?3nw;  
issues, and an international advisory board meets with the database staff to provide additional _ReQQti[
 
guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting Dihk8qJ/6  
data at the three sites. 982$d<0%  
The Collaboration created a Feature Table Definition [http://www.ncbi.nlm.nih.gov/collab/FT/ eE&
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index.html] that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. DGU$3w  
The purpose of this document is to standardize annotation across the databases. The presentation 5}m2D='  
and format of the data are different in the three databases, however, the underlying biological infor- |!}$V  
mation is the same. &EQov9P7  
Confidentiality of Data r dK.*oT  
When scientists submit data to GenBank, they have the opportunity to keep their data confidential ?832#a?FZ;  
for a specified period of time. This helps to allay concerns that the availability of their data in Gen- k@Hu0x  
Bank before publication may compromise their work. When the article containing the citation of the wy^>i$
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sequence or its Accession number is published, the sequence record is released. The database 53L)+\7w  
staff request that submitters notify GenBank of the date of publication so that the sequence can be &pCKz[Yf+  
released without delay. The request to release should be sent to gb-admin@ncbi.nlm.nih.gov. !XFN/-Q ,  
Direct Submissions n\ IVpgP  
The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence E5o0^^  
with annotations. The annotations are meant to provide an adequate representation of the biological l"cYW9  
information in the record. The GenBank Feature Table Definition [http://www.ncbi.nlm.nih.gov/col- ZK13[_@9  
lab/FT/index.html] describes the various features and subsequent qualifiers agreed upon by the 'C[gcp  
International Nucleotide Sequence Database Collaboration. 2<y -c Q?>  
Currently, only nucleotide sequences are accepted for direct submission to GenBank. These GxvVh71zP  
include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or HloP NE&}  
multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a 2/;
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NCBI Handbook GenBank N8KHNTb-M  
protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the uZqo"  
CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession num- eo@:@O+bm  
ber (/protein_id) is assigned to the translation product, which will subsequently be added to the t$}+oCnkv  
protein databases. :cOwTW?Fj  
Multiple sequences can be submitted together. Such batch submissions of non-related sequen- c d:O@)i  
ces may be processed together but will be displayed in Entrez (Chapter 15) as single records. A\=:h AQ  
Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several >8RIMW2  
sequences are biologically related. Such sequences are classified as environmental sample sets, mX<D]Z<
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population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set H\O|Y@uVr  
is assigned its own Accession number and can be viewed independently in Entrez. However, with |C5i3?  
the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus MxCs0::
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allowing scientists to view the relationship between the sequences. %2>FS
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What defines a set? Environmental sample, population, phylogenetic, and mutation sets all jSddjs  
contain a group of sequences that spans the same gene or region of the genome. Environmental p*>[6{$3)O  
samples are derived from a group of unclassified or unknown organisms. A population set contains KKOu" :b  
sequences from different isolates of the same organism. A phylogenetic set contains sequences oiklRf  
from different organisms that are used to determine the phylogenetic relationship between them. ;aD_^XY  
Sequencing multiple mutations within a single gene gives rise to a mutation set. q6osRK*20  
All sets, except segmented sets, may contain an alignment of the sequences within them and xvgIYc{  
might include external sequences already present in the database. In fact, the submitter can begin ; I=z  
with an existing alignment to create a submission to the database using the Sequin submission tool. ;T/' CD  
Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Con- Q(%uDUg%  
tiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez. bf}r8$,  
Segmented sets are a collection of noncontiguous sequences that cover a specified genetic C@KYg/nYw  
region. The most common example is a set of genomic sequences containing exons from a single &qo'ge8p  
gene where part or all of the intervening regions have not been sequenced. Each member record ?lbX.+  
within the set contains the appropriate annotation, exon features in this case. However, the mRNA ;7qk9rz4  
and CDS will be annotated as joined features across the individual records. Segmented sets them- 8o~
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selves can be part of an environmental sample, population, phylogenetic, or mutation set.