IMGT-ONTOLOGY and IMGT-Choreography: foundations of a systemic approach for immunogenetics and immunoinformatics – IMGT

IMGT®, the international ImMunoGeneTics information system® (http://imgt.cines.fr), has for goal to provide, at the international level, a unique source of knowledge in immunogenetics and immunoinformatics. Immunogenetics is the science that integrates genetics and immunology in order to study the immune responses. It includes the study of the genes and proteins, involved in the innate immune responses (of every living organism), and in the adaptive immune responses (of the vertebrates). Molecular immunogenetics has blossomed considerably since 1979, when Tonegawa showed that the considerable and extremely diverse repertoire of antigen receptors [1012 immunoglobulins (IG) or antibodies, and 1012 different T cell receptors (TR) per individual, in human] results from complex rearrangement mechanisms at the DNA level. To the complexity of these mechanisms, must be also added the incredible diversity due to the somatic hypermutations of IG, and a considerable polymorphism of major histocompatibility complex (MHC) - designated as HLA, in human - which is particularly important for bone marrow and organ transplantation. IMGT® was created in 1989 at Montpellier (Université Montpellier II and CNRS) to manage these complex and heterogenous data. IMGT® is the first and, to date, the only integrated information system in immunogenetics and immunoinformatics. There is no other equivalent in the world. IMGT® is the international reference in the domain. IMGT® is a trademark of CNRS (France, EC, Canada and USA). IMGT® is specialized in the sequences, structures and genetic data of IG, TR and MHC. These proteins, 450 to 500 million years old , are characteristic of the adaptive immune responses in vertebrates. They allow a very fine specific recognition of the non self represented by infectious pathogens, viruses, bacteria, parasites and their products (toxins...), and by vaccine and tumoral antigens. IMGT® is also specialized in the proteins of the immunoglobulin superfamily (IgSF) and of the MHC superfamily (MhcSF), and in the related proteins of the immune system (RPI). IMGT® is composed of several databases (four of sequences, one of genes, one of three-dimensional 3D structures), of Web resources which include more than 8,000 HTML pages, and of interactive tools for the processing and the analysis of sequence and 3D structures data. Thus, IMGT® constitutes a unique resource, offering to the researchers and to the clinicians, a common access to standardized genomic, genetic and structural data, resulting from a high level of curation expertise, and interactive tools for their analysis. Standardization is based on IMGT-ONTOLOGY, the first and so far unique ontology in immunogenetics and immunoinformatics. The IMGT® Web server at Montpellier receives an average of more than 150,000 requests per month, coming in equal parts from Europe, the United States and the rest of the world. The project has two major objectives: The first one, is by a muti-disciplinary approach, to identify and characterize new concepts in IMGT-ONTOLOGY to understand the complexity of the immune responses at different scales (molecular, cellular, organism) and to grasp the principles that control the dynamic organization and quality-control of the adaptive immune system (a fine-tuned response between autoimmune diseases and efficiency to fight infections and tumours), in time and space. For interoperability with other major medical or biological ontologies (UMLS, GO, SO, FUGO, MGED, IEDB ontology, etc.), IMGT-ONTOLOGY, including the new concepts, will be formalized with the Web Ontology Language OWL using the Protégé and OBO ontology editors. The second objective is, in a context of systemic approach, the creation of a continuum by dynamic interactions between the IMGT® tools and databases. We have chosen to use the Web Services (created in January 2002) as they permit an external client program (as a database or a tool) to access information or to set up p.