BMC Genomics 2006, 7:300 http://www.biomedcentral.com/1471-2164/7/300 Database schema). Grouped around these central tables are tables for literature and sequencing projects as well as taxonomy and predicted domains. Data entry is done using the iiwi system (Odronitz F., Lampetsdoerfer T., Dietrich D., unpublished results [21]) allowing for remote editing and access control. The sequence table stores the protein sequence and the corresponding sequence as derived from the multiple sequence alignment of the protein (see Import/Export). By relating a position in the alignment to the positions in a set of protein sequences it is possible to retrieve homol- ogous stretches from different sequences. In addition there are fields for sequence classification and nomencla- ture, comments, legacy names, information about the completeness of the sequence, its potential to be a pseudo-gene, and links to records in NCBI's nucleotide and protein databases [20]. The comment field is one of the most important fields intended to contain informa- tion about differences of the database sequences to pub- lished sequences that may have resulted from wrong exon predictions or sequencing errors. Records in the sequence table are related to tables for proteins, species, and publi- cations. Several versions can be assigned to each sequence so changes and corrections can be tracked as more informa- tion becomes available. Furthermore, there are links to tables containing automatically generated protein domain predictions (see Automated processes). Species are defined by a set of names. There are fields for the scientific name of a species, the species abbreviation as used to identify database sequences, and common names. As some species are known by different scientific names, fields containing alternatively used names are also included. To account for the different usage of the scien- tific names, all possible names are listed and linked to the corresponding reference record wherever species are listed or used for selection via the interface. A comment field may contain general information about the correspond- ing species, the specific strain used, or common and diver- gent features compared to closely related organisms. The taxonomy field is converted automatically into a hierar- chical representation of the taxa. (see Automated proc- esses) Proteins are stored with their name and abbreviation as used in the database. Furthermore, classes of a certain pro- tein can be grouped and categorized according to aspects like cellular function or localization. The project table includes information about the sequencing centres including type of data and completeness. Publications can be related either to a sequence to provide additional links to biological information or to a sequencing project. Automated processes The database can trigger external programs upon insertion or update of certain fields in the database tables by con- tacting the delegation server program, which can in turn write computed data to the database (Fig. 1). When a pro- tein sequence is inserted or changed a hmmpfam [22] process is started scanning this sequence for putative domains with Pfam [18] profiles. The obtained domain identifier and the start and end positions together with the E-value are stored in a database table. Upon insertion of a new species record, the content of the taxonomy field is automatically converted into a tree-representation of interrelated taxon records. Each record contains the name of the taxon, and a reference to the parent taxon. Then the species record is connected to the common taxonomic tree. This tree representation of the taxonomy allows for convenient searching, browsing and selection of sub-trees (Fig. 2). Import/export functions Files containing protein sequences in FASTA-format can be imported into the database to update existing or insert new records in the sequence table (Fig. 1). A naming con- vention at all levels ensures the correct assignment of sequences in a FASTA file to sequence records in the data- base. The sequence identifiers are a concatenation of spe- cies name abbreviation, protein name abbreviation, protein class and protein variant. In contrast to the usage of numerical database IDs, the naming convention thus immediately provides the user with information about the phylogenetic relation and possible functions of the protein. Sequences and sequence alignments can be exported from the database using filters to include only certain proteins, protein classes, or sequences from species in certain taxa. The resulting FASTA file also follows the naming convention and therefore can be re-imported after editing. Thus it is possible to retrieve a multiple sequence alignment from the database, edit it manually and write it back to the database. During import, sequences with identifiers that do not match any record in the database, induce the creation of a new database record according to the information included in the identifier. Utility and discussion The requirements for Pfarao can be summarized as fol- lows: The key component of the database is the protein sequence that is obtained by manual annotation of genome and EST data with the help of a multiple sequence alignment. The sequence needs to be connected to data that allows the useful interpretation of the results concerning its biological function, and it needs to be Page 3 of 8 (page number not for citation purposes)