GenBank: The Nucleotide Sequence Database

1. GenBank: The Nucleotide Sequence Database y2^Y/)   
Ilene Mizrachi Hhcpp7cr'  
Created: October 9, 2002 E S//
  
Updated: August 22, 2007 0"pAN[=K@  
Summary `)_dS&_\  
The GenBank sequence database is an annotated collection of all publicly available nucleotide a m|F?|1  
sequences and their protein translations. This database is produced at National Center for .N ,3od@  
Biotechnology Information (NCBI) as part of an international collaboration with the European Molecular zN^n]N_?  
Biology Laboratory (EMBL) Data Library from the European Bioinformatics Institute (EBI) and the DNA ^rifRY-,yO  
Data Bank of Japan (DDBJ). GenBank and its collaborators receive sequences produced in 6G[4rD&  
laboratories throughout the world from more than 100,000 distinct organisms. GenBank continues to 0.8
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grow at an exponential rate, doubling every 10 months. Release 134, produced in February 2003, o!kbK#k  
contained over 29.3 billion nucleotide bases in more than 23.0 million sequences. GenBank is built =A83W/4  
by direct submissions from individual laboratories, as well as from bulk submissions from large-scale qVH1}9_  
sequencing centers. \1D<!k\S  
Direct submissions are made to GenBank using BankIt [http://www.ncbi.nlm.nih.gov/BankIt/], H|3:6x  
which is a Web-based form, or the stand-alone submission program, Sequin [http:// U:^PC x`  
www.ncbi.nlm.nih.gov/Sequin/index.html]. Upon receipt of a sequence submission, the GenBank staff t gI{`jS%  
assigns an Accession number to the sequence and performs quality assurance checks. The j+ $rj  
submissions are then released to the public database, where the entries are retrievable by Entrez or ,$s8GAmq  
downloadable by FTP. Bulk submissions of Expressed Sequence Tag (EST), Sequence Tagged Site ]>=}*=  
(STS), Genome Survey Sequence (GSS), and High-Throughput Genome Sequence (HTGS) data are -?V-*jI  
most often submitted by large-scale sequencing centers. The GenBank direct submissions group also (k5We!4[1  
processes complete microbial genome sequences. ;f#v0W`5  
History }dgfqq  
Initially, GenBank was built and maintained at Los Alamos National Laboratory (LANL). In the early QdF5Cwf4  
1990s, this responsibility was awarded to NCBI through congressional mandate. NCBI undertook a&/#X9/  
the task of scanning the literature for sequences and manually typing the sequences into the data- 2^h27A  
base. Staff then added annotation to these records, based upon information in the published article. D$ dfNiCH  
Scanning sequences from the literature and placing them into GenBank is now a rare occurrence. g jDh?I  
Nearly all of the sequences are now deposited directly by the labs that generate the sequences.  D~S<U  
This is attributable to, in part, a requirement by most journal publishers that nucleotide sequences BJ$9vbhZN  
are first deposited into publicly available databases (DDBJ/EMBL/GenBank) so that the Accession 0
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number can be cited and the sequence can be retrieved when the article is published. NCBI began + jc!5i .  
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NCBI Handbook GenBank _x%7@.TB  
accepting direct submissions to GenBank in 1993 and received data from LANL until 1996. Cur- _=_Px@ <Q  
rently, NCBI receives and processes about 20,000 direct submission sequences per month, in vQosPS_2L  
addition to the approximately 200,000 bulk submissions that are processed automatically. *H"B _3<n  
International Collaboration PRu 6xsyA  
In the mid-1990s, the GenBank database became part of the International Nucleotide Sequence KHe=O1 %QO  
Database Collaboration with the EMBL database (European Bioinformatics Institute [http:// K1mPr^3rC  
www.ebi.ac.uk/], Hinxton, United Kingdom) and the Genome Sequence Database (GSDB; LANL, ALrw\qV  
Los Alamos, NM). Subsequently, the GSDB was removed from the Collaboration (by the National "& ])lz[
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Center for Genome Resources, Santa Fe, NM), and DDBJ [http://www.ddbj.nig.ac.jp/] (Mishima, 1"zDin!A  
Japan) joined the group. Each database has its own set of submission and retrieval tools, but the +giyX7BPJ  
three databases exchange data daily so that all three databases should contain the same set of Zn&, t &z  
sequences. Members of the DDBJ, EMBL, and GenBank staff meet annually to discuss technical sy:[T T!w  
issues, and an international advisory board meets with the database staff to provide additional -I*^-+>H  
guidance. An entry can only be updated by the database that initially prepared it to avoid conflicting d4u})  
data at the three sites. 7S '% E  
The Collaboration created a Feature Table Definition [http://www.ncbi.nlm.nih.gov/collab/FT/ fol,xMc&  
index.html] that outlines legal features and syntax for the DDBJ, EMBL, and GenBank feature tables. nygbt<;?  
The purpose of this document is to standardize annotation across the databases. The presentation RN$1bxY  
and format of the data are different in the three databases, however, the underlying biological infor- @Z* W  
mation is the same. tjIl-IQ  
Confidentiality of Data l)G^cSHF.3  
When scientists submit data to GenBank, they have the opportunity to keep their data confidential Eo{"9j\  
for a specified period of time. This helps to allay concerns that the availability of their data in Gen- . <jr0,i  
Bank before publication may compromise their work. When the article containing the citation of the Li!Vx1p;u.  
sequence or its Accession number is published, the sequence record is released. The database 61SlVec*o8  
staff request that submitters notify GenBank of the date of publication so that the sequence can be C"6?bg5N  
released without delay. The request to release should be sent to gb-admin@ncbi.nlm.nih.gov. sF|5XjQ  
Direct Submissions RHmgD;7`  
The typical GenBank submission consists of a single, contiguous stretch of DNA or RNA sequence C<NLE-  
with annotations. The annotations are meant to provide an adequate representation of the biological -8; 7Sp1  
information in the record. The GenBank Feature Table Definition [http://www.ncbi.nlm.nih.gov/col- l n{e1':$"  
lab/FT/index.html] describes the various features and subsequent qualifiers agreed upon by the 7op`s5i  
International Nucleotide Sequence Database Collaboration. #yI mKEYX  
Currently, only nucleotide sequences are accepted for direct submission to GenBank. These .n#@$ nGZ  
include mRNA sequences with coding regions, fragments of genomic DNA with a single gene or A#Iyb){Y  
multiple genes, and ribosomal RNA gene clusters. If part of the nucleotide sequence encodes a gW^VVbB'L  
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NCBI Handbook GenBank +1uF !G&l  
protein, a conceptual translation, called a CDS (coding sequence), is annotated. The span of the 6ys &zy  
CDS feature is mapped to the nucleotide sequence encoding the protein. A protein Accession num- gnFr}L&j  
ber (/protein_id) is assigned to the translation product, which will subsequently be added to the Q9~*<I> h;  
protein databases. qlb- jL  
Multiple sequences can be submitted together. Such batch submissions of non-related sequen- q@Zn|NR  
ces may be processed together but will be displayed in Entrez (Chapter 15) as single records. z2MWN\?8  
Alternatively, by using the Sequin submission tool (Chapter 12), a submitter can specify that several =7w\ 7-.m  
sequences are biologically related. Such sequences are classified as environmental sample sets, ZX>AE3wk  
population sets, phylogenetic sets, mutation sets, or segmented sets. Each sequence within a set ix([mQg  
is assigned its own Accession number and can be viewed independently in Entrez. However, with xC{qV,  
the exception of segmented sets, each set is also indexed within the PopSet division of Entrez, thus @CTgT-0!  
allowing scientists to view the relationship between the sequences. 6%t1bM a  
What defines a set? Environmental sample, population, phylogenetic, and mutation sets all ]Bcp;D  
contain a group of sequences that spans the same gene or region of the genome. Environmental /LvRP yj@  
samples are derived from a group of unclassified or unknown organisms. A population set contains d/ARm-D  
sequences from different isolates of the same organism. A phylogenetic set contains sequences 8dO!  
from different organisms that are used to determine the phylogenetic relationship between them. %e-7 ubW  
Sequencing multiple mutations within a single gene gives rise to a mutation set. eCqHvMp  
All sets, except segmented sets, may contain an alignment of the sequences within them and t; 4] cg:_  
might include external sequences already present in the database. In fact, the submitter can begin <J`0mVOX  
with an existing alignment to create a submission to the database using the Sequin submission tool. eM$
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Currently, Sequin accepts FASTA+GAP, PHYLIP, MACAW, NEXUS Interleaved, and NEXUS Con- W8ouO+wK  
tiguous alignments. Submitted alignments will be displayed in the PopSet section of Entrez. oXb;w@:  
Segmented sets are a collection of noncontiguous sequences that cover a specified genetic h-G)o[MA  
region. The most common example is a set of genomic sequences containing exons from a single x[$z({Yf  
gene where part or all of the intervening regions have not been sequenced. Each member record S 5/R_5  
within the set contains the appropriate annotation, exon features in this case. However, the mRNA ZZHDp&lh }  
and CDS will be annotated as joined features across the individual records. Segmented sets them- $6mX  
selves can be part of an environmental sample, population, phylogenetic, or mutation set.