Annotation-based searches

It is estimated that the amount of genomic data collected and analyzed doubles yearly. Without suitable databases, it would be difficult to use the results of genome sequencing. The journal Nucleic Acids Research publishes an aimual database issue with reviews covering all databases freely available (the exception being for databases that provide limited access for those who choose not to register). Those databases provide annotation-based searches with the option (links to other websites) to perform sequence similarity... 

The protein sequence database is also a text-numeric database with bibliographic links. It is the largest public domain protein sequence database. The current PIR-PSD release 75.04 (March, 2003) contains more than 280 000 entries of partial or complete protein sequences with information on functionalities of the protein, taxonomy (description of the biological source of the protein), sequence properties, experimental analyses, and bibliographic references. Queries can be started as a text-based search or a sequence similarity search. PIR-PSD contains annotated protein sequences with a superfamily/family classification. 

From genome sequences, a plethora of DNA sequence information is, often publicly, accessible in databases. Pieces of genome sequence have often been annotated, based on sequence similarity to other genes with similar function, to possess a certain function. From the gene sequence, the corresponding protein sequence of a putative enzyme can of course be readily derived so that at this stage the target of the search for a new enzyme is defined. 

The mentioned data management systems are only first steps toward comprehensive lipid databases and global lipid networks. An example for such a data bank is LIPIDMAPS (http //www.lipidmaps.org), which covers structures and annotations of biologically relevant lipids (43). The structures originate from the core laboratories of the LIPIDMAPS consortium and their partners. In this database, users can search the LIPID MAPS proteome database using either text-based or structure-based search options. In addition to LIPIDMAPS, other databases in Europe (http //www.lipidomics.net) and Japan (http //www.lipidbank.jp) have been initiated. 

The full Swissprot sequences (25, 26) are searched against the purified unique set of the PDB sequences. Three-dimensional (3D) domains are annotated based on PDB sequence boundaries, and their structures are clustered to 95% sequence identity. 

In addition to a classification-based retrieval of lipids, users can search LMSD using either text-based or structure-based search options. The text-based search implementation supports data retrieval by any combination of these data fields Lipid MAPS ID, systematic or common name, mass, formula, category, main class, and subclass data fields. The structure-based search, in conjunction with optional data fields, provides the capability to perform a substmcture search or exact match for the structure drawn by the user. Search results, in addition to structure and annotations, also include relevant links to external databases. 

The second postprocessing step is the automated enhancement of the TrEMBL annotation to bring TrEMBL entries closer to SWISS-PROT standard. There is an increasing need for reliable automatic functional annotation to cope with the rapidly increasing amount of sequence data. Most of the current approaches are still based on sequence similarity searches against known proteins. Some groups try to collect the results of different prediction tools in a simple way, e.g., PEDANT (Frishman and Mewes, 1997) or GeneQuiz (Scharf et al., 1994). However, several pitfalls of these methods have been reported (Bork and Koonin, 1998). 

Because licensed vaccines are the focus of much attention in the public as well as in the vaccine research community, VIOLIN has two subdatabases that focus on licensed human and animal vaccines. The Huvax subdatabase (http //www.violinet.org/huvax) stores all licensed human vaccines in the USA and Canada. The data for these licensed human vaccines are annotated through manual curation and a vigorous review process. Huvax includes manually curated data including manufacturer, trade name, storage information, age at which the vaccine should be administered, and other relevant information. These vaccines are also listed by the CDC CVX codes (codes that indicate the product used in a vaccine) for tracking vaccination records. Huvax has provided cross-references based on these CDC CVX codes. Huvax provides ways for users to search, compare, and analyze licensed human vaccines. Various criteria can be used for querying human vaccines. Different vaccines can also be compared side by side. Vevax is a VIOLIN database of licensed veterinary vaccines (http //www. violinet.org/vevax). 

Figure 1 Schematic illustration of the proteomics process comprising the utilization of both gel-base and liquid-phase separations interphased to mass spectrometry analysis followed by database search mining, annotation, and a final link to the functional role of proteins.

Advanced search queries based on guideline attributes Annotated bibliography of resources relevant to guideline methodology... 

A full text search of the PDB database to identify structures (pdb ids) by name/keyword Hypertext-based dassification of the PDB into biochemically meaningful contexts Summary and annotation of PDB entries... 

Apart from text searches, both SWISS-PROT and TrEMBL can be queried by sequence analysis tools as well as protein identification and characterization tools. Tools like Peptldent or FindMod (see Section 4.4) take advantage of the annotation of SWISS-PROT/TrEMBL to improve their capacities of identifying and characterizing active chains and proteins annotated to be post-translationally modified. This is better than basing their computations and predictions merely on the precursor protein sequences. 

At the time of writing only two categories available for searching, the chordates (based on the human annotation), and the plants (based on the A. thaliana annotation). Other databases, such as the yeast (based on the annotation of Saccharomyces cerevisiae) and the insect (based on the annotation of Drosophila melanogaster) will be also available in the near future. 

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