Database TREMBL

Swiss-Prot, TrEMBL Annotated non-redundant protein sequence database, TrEMBL is a computer-annotated supplement to Swiss-Prot. TrEMBL contains the translations of all coding sequences present in the EMBL Nucleotide Sequence Database which are no yet integrated into Swiss-Prot... 

Protein databases used to be from direct protein sequencing, but now they are made almost exclusively from the translation of ORFs (Open Reading Frames on DNA sequences). Both the European Bioinformatics Institute (EBI) and National Center for Biotechnology Information (NCBI) provide databases, TREMBL [15] and GENPEPT [19] respectively, which are automatic translations from the CDS features of the DNA in their nucleotide databases. This includes some automated annotation of the role which the protein plays. 

The increasing numbers of stored protein and nucleic acid sequences, and the recognition that functionally related proteins often had similar sequences, catalyzed the development of statistical techniques for sequence comparison which underlie many of the core bioinformatic methods used in proteomics today. Nucleic acid sequences are stored in three primary sequence databases - GenBank, the EMBL nucleotide sequence database, and the DNA database of Japan (DDBJ) - which exchange data every day. These databases also contain protein sequences that have been translated from DNA sequences. A dedicated protein sequence database, SWISS-PROT, was founded in 1986 and contains highly curated data concerning over 70 000 proteins. A related database, TrEMBL, contains automatic translations of the nucleotide sequences in the EMBL database and is not manually curated. 

Bairoch A, Apweiler R (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res 28 45-48... 

TrEMBL (http //www.expasy.org/sprot), database of the European Bioinformatics Institute, translated EMBL. Generated by computer translation of genetic information from the EMBL database. Automatically annotated. 

MSDB (ftp //ftp.ncbi.nih.gov/repository/MSDB), database created especially for MS applications. Contains nonidentical protein sequences obtained from other databases (PIR, TrEMBL, SwissProt). At http // www.matrixscience.com/help/seq db setup msdb.html, a guidebook for MSDB users can be found. 

The protein sequence databases are the most comprehensive source of information on proteins. The goal of this chapter is to describe the different protein sequence databases available to researchers. It is necessary to distinguish between universal databases that cover proteins from all species and specialized data collections that store information about specific families or groups of proteins, or about the proteins of a specific organism. Two categories of universal protein sequence databases can be discerned simple archives of sequence data and annotated databases in which additional information has been added to the sequence record. The next section describes the Protein Information Resource (PIR), the oldest protein sequence database SWISS-PROT, an annotated universal sequence database and TrEMBL, the supplement of... 

The SWISS-PROT and TrEMBL ID lines differ in the first two parts of the ID line. The first part is the entry name "ANP NOTCO" in the case of the SWISS-PROT example and "Q12757" in the TrEMBL example. The entry name used in all SP-TrEMBL entries is always the same as the accession number of the entry. The entry name used in REM-TrEMBL is the Protein ID tagged to the corresponding CDS in the EMBL Nucleotide Sequence Database. To the right of the entry name you will find either "preliminary" (in the TrEMBL entry) or STANDARD (in the SWISS-PROT entry). The data class used in TrEMBL is always PRELIMINARY. That means that the data are thoroughly checked by a computer,... 

The entries from the composite divisions of the EMBL database (HTG, STS, EST, and UNC) are now added to their relative taxonomic TrEMBLnew divisions. Then all hies are searched for entries that have recently been added to SWISS-PROT or TrEMBL and are thus missing a /dbxref = SWISS-PROT or a /dbxref = SPTREMBL qualifier in EMBL. These entries are removed. The entries put in the hies patent.dat, immuno.dat, smalls.dat, synthetic.dat and pseudo.dat are now already at the end of their production line. They are new entries in REM-TrEMBL (REMaining TrEMBL), which contains the entries (about 44,000 in release 10) that will not be included in SWISS-PROT. This section is organized in hve subsections ... 

Immunoglobulins and T-cell receptors (hie name Immuno.dat) Most REM-TrEMBL entries are immunoglobulins and T-cell receptors. The integration of additional immunoglobulins and T-cell receptors into SWISS-PROT has been stopped, because SWISS-PROT does not want to add all known somatic recombined variations of these proteins to the database. Currently there are more than 18,000 immunoglobulins and T-cell receptors in REM-TrEMBL. SWISS-PROT plans to create a specialized database dealing with these sequences as another supplement to SWISS-PROT but will keep only a representative cross section of these proteins in SWISS-PROT. 

These redundancies should not be present in SWISS-PROT or TrEMBL thus it was necessary to find methods to manipulate the data from redundant source databases to meet the stringent standards of minimal redundancy. The objective was to recognize and eliminate the redundancy already present in the databases and to prevent further redundancy entering the database. 

The virtual SWISS-PROT entries have a far-reaching effect on TrEMBL. For example, the virtual entry for the Rubisco (ribulose-bisphosphate carboxylase) large chain affects 3300 TrEMBL entries. Therefore a system has been developed to decompose these virtual entries into rules that are stored in a relational database with proper version control features. 

The ENZYME database (Bairoch, 1996) is also used to generate standardized description lines for enzyme entries and to allow information such as catalytic activity, cofactors, and relevant keywords to be taken from ENZYME and to be added automatically to TrEMBL entries. Additionally, specialized databases such as FlyBase (FlyBase Consortium, 1999) and MGD (Blake et al., 1999) are used to transfer information such as the correct gene nomenclature and cross references to these databases into TrEMBL entries. The automatic analysis and annotation of TrEMBL entries are redone and updated every TrEMBL release. 

This section focuses on the use of SWISS-PROT + TrEMBL for sequence similarity searches. Searches in protein sequence databases have now become a standard research tool in the life sciences. To produce valuable results, the source databases should be comprehensive, nonredundant, well annotated, and up-to-date. However, lack of a single protein sequence database that satisfies all four criteria has previously forced users to perform searches across multiple databases to avoid incomplete results. This strategy normally produces complete but redundant results owing to different versions of the same sequence report in different databases. 

SPTR is distributed in three files sprot.dat.Z, trembl.dat.Z, and trembl new.dat.Z. These files are, as indicated by their Z extension, Unix compress format files, which, when decompressed, produce ASCII files in SWISS-PROT format. Three others files are also available (sprot.fas.Z, trembl.fas.Z, and trembl new.fas.Z), which are compressed fasta format sequence files that are useful for building the databases used by FASTA, BLAST, and other sequence similarity search programs. These files should not be used for other purposes, because all annotation is lost when using this format. The SPTR files are stored in the directory /pub/databases/sp tr nrdb on the EBI FTP server (ftp.ebi.ac.uk) and in the directory /databases/sp tr nrdb on the ExPASyFTP server (ftp. expasy.ch). 

The lower part shows information ofselected protein sequence. The small table shows the results of sequence search against UNIPROT(Swiss-prot/TrEMBL), nr.aa, and UniGene database see Subheading 2, items 2 and 4) using BLAST. 

The ExPASy server (www.expasy.chl is one of the most useful servers, where almost any bioinforma tic tool can be found, together with useful links to other websites such as NCBI or EBI. The several access databases are descriptive, easy to follow, and up to date. Protein data bank searches with SwissProt or Trembl, as well as sequence alignments using either SimAlign (for two sequences) or ClustalW (for more than two protein sequences) can be started from ExPASy, to name just a few of the possibilities available. Access is also given to the Roche Applied Science Biochemical pathways where either keyword searches for particular enzymes or for metabolites can be performed, or entire metabolic pathways or sections thereof can be visualized. Proteomics evaluation is also available on ExPASy, which features free 2D-PAGE software called Melanie. 

Protein (amino acid) sequences are available from databases such as SwissProt/ Trembl or Protein Data Bank (PDB). Most useful is the ability of such databases to perform alignments, the comparison between different sequences. Simple alignment compares two sequences, multiple alignment more than two. 

There are different classes of protein sequence databases. Primary and secondary databases are used to address different aspects of sequence analysis. Composite databases amalgamate a variety of different primary sources to facilitate sequence searching efficiently. The primary structure (amino acid sequence) of a protein is stored in primary databases as linear alphabets that represent the constituent residues. The secondary structure of a protein corresponding to region of local regularity (e.g., a-helices, /1-strands, and turns), which in sequence alignments are often apparent as conserved motifs, is stored in secondary databases as patterns. The tertiary structure of a protein derived from the packing of its secondary structural elements which may form folds and domains is stored in structure databases as sets of atomic coordinates. Some of the most important protein sequence databases are PIR (Protein Information Resource), SWISS-PROT (at EBI and ExPASy), MIPS (Munich Information Center for Protein Sequences), JIPID (Japanese International Protein Sequence Database), and TrEMBL (at EBI). ... 

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). 

SWISS-PROT (Hofmann et al., 1999) is a curated protein sequence database maintained by the Swiss Institute of Bioinfornmatics and is a collaborative partner of EMBL. The database consists of SWISS-PROT and TrEMBL, which consists of entries in SWISS-PROT-like format derived from the translation of all CDS in the... 

EMBL Nucleotide Sequence Database. SWISS-PROT consists of core sequence data with minimal redundancy, citation and extensive annotations including protein function, post-translational modifications, domain sites, protein structural information, diseases associated with protein deficiencies and variants. SWISS-PROT and TrEMBL are available at EBI site, http //www.ebi.ac.uk/swissprot/, and ExPASy site, http //www.expasy.ch/sprot/. From the SWISS-PROT and TrEMBL page of ExPASy site, click Full text search (under Access to SWISS-PROT and TrEMBL) to open the search page (Figure 11.3). Enter the keyword string (use Boolean expression if required), check SWISS-PROT box, and click the Submit button. Select the desired entry from the returned list to view the annotated sequence data in Swiss-Prot format. An output in the fasta format can be requested. Links to BLAST, feature table, some ExPASy proteomic tools (e.g., Compute pI/Mw, ProtParam, ProfileScan, ProtScale, PeptideMass, ScanProsite), and structure (SWISS-MODEL) are provided on the page. 

---