Bioinformatics sequence databases

EMBL European Bioinformatics Institute nucleotide sequence database biblio., sub- stance, se- quence 20mio nucleotide seq., 28billion nucleotides journals, author submis- sions European Bioinformatics Institute free daily http //www.e- hi.ac.uk/embl/ index.html... 

Sequences of the genes/cDNAs can be retrieved from databases on the Internet at various web sites. For example, GeneBank (at the National Center for Biotechnology Information, NCBI) is at http //www.ncbi.nlm.nih.gov/ Web/Search/index.html. The EMBL Nucleotide Sequence database (through the European Bioinformatic Institute, EBI) can be found at http //www.ebi.ac.uk/queries/queries.html, whilst that of the DNA Data Bank of Japan is at http //www.ddbj.nig.ac.jp/. 

SWISS-PROT (Bairoch and Apweiler, 1999) is an annotated protein sequence database established in 1986 and maintained collaboratively by the Swiss Institute of Bioinformatics and the EMBL Outstation, The European Bioinformatics Institute (EBI). It strives to provide a high level of annotation, a minimal level of redundancy, a high level of... 

ExPASy (Expert Protein Analysis System, www.expasy.ch) or the National Centre for Biotechnology Information (NCBI, www.ncbi.nlm.gov) websites. Both websites provide bioinformatics tools, links to sequence databases and extensive bibliographic resources. As an example of the wealth of information available on individual enzymes, at the time of writing a search based on nitrilase in the Entrez protein section of NCBI will recover more than 10000 references to nitrilase enzyme amino acid sequences. These can be rapidly screened online by organism, and the individual entries will have links to amino acid and gene sequence, relevant literature and information on protein features (such as conserved domains). 

As determined by a search of the European Bioinformatics Institute (http //www.ebi.ac.uk/) protein sequence databases. 

Selected entries from Methods in Enzymology [vol, page(s)] Databases and Resources Information services of European Bioinformatics Institute, 266, 3 TDB new databases for biological discovery, 266, 27 PIR-international protein sequence database, 266, 41 superfamily classification in PIR-international protein sequence database, 266, 59 gene classification artificial neural system, 266, 71 blocks database and its applications, 266, 88 indexing and using sequence databases, 266, 105 SRS information retrieval system for molecular biology data banks, 266, 114. 

One of the central activities of the European Bioinformatics Institute (EBI) (Emmert et ah, 1994) is development and distribution of the EMBL nucleotide sequence database (Stoesser et ah, 2001). This is a collaborative project with GenBank (NCBI, USA) and DDBJ (DNA database of Japan) to ensure that all the new and updated database entries are shared between the groups on a daily basis. The search of sequence databases and an access to various application tools can be approached from the home page of EBI at http //www.ebi.ac.uk/ (Figure 3.3). 

SWISS-PROT (Bairoch and Apweiler, 2000) is a protein sequence database that, from its inception in 1986, was produced collaboratively by the Department of Medical Biochemistry at the University of Geneva and the EMBL. The database is now maintained collaboratively by Swiss Institute of Bioinformatics (SIB) and EBI/EMBL. SWISS-PROT provides high-level annotations, including descriptions of the function of the protein and of the structure of its domains, its post-translational modifications, its variants, and so on. The database can be accessed from http //expasy.hcuge.ch/sprot/sprot-top.html or numerous mirror sites. In 1966, Translated EMBL (TrEMBL) was created as a computer-annotated supplement to SWISS-PROT (Bleasby et al, 1994). 

The Protein Data Bank (PDB) is the primary structure database serving as the international repository for the processing and distribution of 3D structures of biomacromolecules (Bernstein et al, 1977). The database is operated by the Research Collaboratory for Structural Bioinformatics (RCSB) and is accessible from the primary RCSB site at http //www.rcsb.org/pdb/ (Berman et al., 2000). Most of the structure fold/motif/domain databases (Conte et al., 2000) and analysis servers (Brenner et al, 2000 Hofmann et al, 2000 Kelley et al., 2000 Shi et al., 2001) utilize 3D-structure information from PDB and sequence information from primary sequence databases. Some of these databases/analysis servers and their URL are listed in Table 12.3. 

Adding value to sequence databases through bioinformatics... 

Gracy, J. Argos, P. (1999). Automated protein sequence database classification. I. Integration of compositional similarity search, local similarity search, and multiple sequence alignment. Bioinformatics 14,164-73. 

The National Center for Biotechnology Information (NCBI). Located at the National Library of Medicine in Bethesda, MD, USA. The home of the GenBank DNA sequence database PubMed literature search engine sequence search tools (e.g., PSI-BLAST) genomic sequence navigation tools. A substantial repository of resources in all areas of bioinformatics. 

The European Bioinformatics Institute (EBI). This site is located at Hinxton Hall, Cambridge, UK. The home of the EMBL Nucleotide Sequence Database data management tools [including publicly accessible version of SRS—the Sequence Retrieval System (7)] protein family databases microarray tools etc. An extensive repository of resources for bioinformatics. 

Products/technologies These include proprietary high-throughput multiplex DNA sequencing positional cloning bioinformatics bacterial genomics PathoGenome sequence database. 

International Nucleotide Sequence Database. URL http // www.ddbj.nig.ac.jp/. A joint compilation of heterogeneous sequence data into a redundant database. New and updated data shared daily by DNA Database of Japan (DDBJ). European Molecular Biology Laboratory, European Bioinformatics Institute EMBL-EBD- Cambridge, U.K. URL http // www.ebi.ac.uk/Databases/. GenBank. NCBI. URL http // www.ncbi.nlm.nih.gov/Genbank/GenbankSearch.html. 

These protein attributes are then submitted to a database search. This search identifies a protein by looking at the best match between experimental data and data obtained by in-silico processing and digestion of a protein sequence database. The identification and characterization procedures using bioinformatics tools will be the topic of Section 4.4. 

Once the spots of interest in a 2-DE gel are selected, the next step is to identify the corresponding proteins in a database. This is another challenge for bioinformatics to design tools adapted to match experimental data with those in sequence databases. Even if the amino acid sequence of a protein can be predicted with a reasonable degree of confidence, post-translational protein modifications cannot always be predicted from the DNA sequence and their presence or absence can be of paramount importance for the final structure, as well as for the function or dysfunction of a protein. Powerful protein identification tools therefore have to take into account information about known post-translational modifications wherever possible. 

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