The first public release of the IMGT/HLA Database (8
) was made on the 16th December 1998 and was included on the European Bioinformatics Institute's (EBI) Server as part of the IMGT project. The database is now updated quarterly and with each release all the tools are updated to include the new sequences and information on all the new and modified sequences is reported. The IMGT/HLA website provides tools for both the retrieval of HLA sequences and also the manipulation and analysis of these sequences. In addition a large amount of background information is held on the source material from which the sequences were derived. The two main uses of the website are to retrieve information on a single allele or to view sequence alignments based on the official HLA sequences, see Figure .
Figure 1 Alignment formats available from the IMGT/HLA and IMGT/MHC Database. The examples shown are based on alignment (A) which shows seven DRB1*01 alleles. In these alignments a dash (−) indicates identity to the reference sequence (more ...)
Using the ‘Allele Query Tool’ users can retrieve information about any allele. The tool provides an interface for retrieving the information that is easy to use, requiring either the allele name, a synonym or previous designation, or a single EMBL/GenBank/DDBJ accession number. The output includes all the information provided in the official WHO Nomenclature Reports as well as other information on the individual and cells from which the sequence was derived. The entry also provides links to all EMBL/GenBank/DDBJ entries. References are also provided for all alleles and where possible linked to the abstract of the paper in which the allele is first described, as provided by PubMed. The nucleotide and protein sequences are also provided in the standard format used in the IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla/nomen_pt2.html
The database provides a tool for viewing sequence alignments based on the official HLA sequences. The interface provided lets the user define a number of key variables. The basic steps in selecting an alignment are to choose the loci and the type of sequence. The types of alignment available currently include coding sequences, genomic sequences and amino acid sequences. The remaining options available allow the user to customize the output to include optional reference sequences, sequence display and selection of specific sequences.
The database also provides a range of search tools. Through a collaboration with the EBI, users can search the IMGT/HLA database using the SRS Browser (10
). Sequence similarity searches can also be performed using the BLAST (11
) and FASTA (12
) search tools. It is therefore recommended that for sequence similarity searches the IMGT/HLA database should be used wherever possible. BLAST searches using EMBL or other databases cannot guarantee to match against the official sequences.
Whilst most use of the database is confined to the sequence data, the database also contains additional background information, for example on the cells from which the alleles were characterized. Search and retrieval tools are provided to allow the user to query the data on all the cells from which a particular alleles has been sequenced. The IMGT/HLA database provides several tools to support the work of HLA typing laboratories, for example the characterization of ambiguities in Sequence Based Typing (SBT). Most SBT typing strategies currently employed use the exon 2 and exon 3 sequences for HLA class I analysis and exon 2 alone for HLA class II analysis. Due to the heterozygous nature of the SBT analysis the combinations of many pairs of alleles may give an ambiguous typing result. To aid the interpretation of SBT results, the database provides a comprehensive list of the ambiguous combinations for each locus.
As well as providing HLA sequences for retrieval, the IMGT/HLA website also provides the tools for submitting both new and confirmatory sequences to the WHO HLA Nomenclature Committee. This is now the only accepted method for submitting new sequences to the database. On submission of a sequence it is automatically analysed and annotated and then given a name, before been loaded into the IMGT/HLA database and included in the monthly nomenclature reports (13
). The submission tool can be used for both new and confirmatory sequences, and is capable of holding confidential entries until a set time, thus allowing alleles to be named before publication. The submission of new HLA sequences to the IMGT/HLA database does not replace the submission of these sequences to EMBL/GenBank/DDBJ, as the submission criteria state that the sequences must also have been submitted to these databases.