IMGT,the international ImMunoGeneTics database

The international ImMunoGeneTics database (IMGT) (http://imgt.cines.fr), is a high quality integrated information system specializing in Immunoglobulins (IG), T cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and other vertebrates, created in 1989, by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM), at the Université Montpellier II, CNRS, Montpellier, France. IMGT provides a common access to standardized data which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes three sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) with different interfaces (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView), one 3D structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages ('IMGT Marie-Paule page') and interactive tools for sequence analysis (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/Allele-Align, IMGT/PhyloGene). IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on IMGT-ONTOLOGY. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in physiological normal and pathological situations. IMGT has important applications in medical research (autoimmune diseases, AIDS, leukemias, lymphomas, myelomas), biotechnology related to antibody engineering (phage displays, combinatorial libraries) and thera-peutic approaches (graft, immunotherapy). IMGT is freely available at http://imgt.cines.fr.     

IMGT, the international ImMunoGeneTics database

IMGT, the international ImMunoGeneTics database (http://imgt.cines. fr:8104 ), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr ). At present, IMGT includes two databases: IMGT/LIGM-DB, a comprehensive database of Ig and TcR from human and other vertebrates, with translation for fully annotated sequences, and IMGT/HLA-DB, a database of the human MHC referred to as HLA (Human Leucocyte Antigens). The IMGT server provides a common access to expertized genomic, proteomic, structural and polymorphic data of Ig and TcR molecules of all vertebrates. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cines.fr:8104. The IMGT Index is provided at the IMGT Marie-Paule page (http://imgt.cines.fr:8104/textes/IMGTindex.html).     

IMGT, the international ImMunoGeneTics database.

IMGT, the international ImMunoGeneTics database (http://imgt.cnusc. fr:8104), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr). IMGT comprises three databases: LIGM-DB, a comprehensive database of Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development); a tool, IMGT/DNAPLOT, developed for sequence analysis and alignments; and expertised data based on the IMGT scientific chart, the IMGT repertoire. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc. fr:8104     

IMGT-Choreography for immunogenetics and immunoinformatics

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), was created in 1989 at Montpellier, France. IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) which belong to the immunoglobulin superfamily (IgSF) and MHC superfamily (MhcSF). IMGT provides a common access to standardized data from genome, proteome, genetics and three-dimensional structures. The accuracy and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic specification of terms to be used in immunogenetics and immunoinformatics. IMGT-ONTOLOGY has been formalized using XML Schema (IMGT-ML) for interoperability with other information systems. We are developing Web services to automatically query IMGT databases and tools. This is the first step towards IMGT-Choreography which will trigger and coordinate dynamic interactions between IMGT Web services to process complex significant biological and clinical requests. IMGT-Choreography will further increase the IMGT leadership in immunogenetics and immunoinformatics for medical research (repertoire analysis of the IG antibody sites and of the TR recognition sites in autoimmune and infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild life species), genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (detection and follow up of residual diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT is freely available at http://imgt.cines.fr.     

IMGT®, the International ImMunoGeneTics Information System® for Immunoinformatics

IMGT, the International ImMunoGeneTics information system ( http://imgt.cines.fr ), was created in 1989 by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM) (Université Montpellier 2 and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. IMGT is recognized as the international reference in immunogenetics and immunoinformatics. IMGT is a high quality integrated knowledge resource, specialized in (i) the immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates; (ii) proteins that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF); and (iii) related proteins of the immune systems (RPI) of any species. IMGT provides a common access to standardized data from genome, proteome, genetics, and three-dimensional (3D) structures for the IG, TR, MHC, IgSF, MhcSF, and RPI. IMGT interactive on-line tools are provided for genome, sequence, and 3D structure analysis. IMGT Web resources comprise 10,000 HTML pages of synthesis and knowledge (IMGT Scientific chart, IMGT Repertoire, IMGT Education, etc.) and external links (IMGT Bloc-notes and IMGT other accesses).     

IMGT, the international ImMunoGeneTics database

IMGT, the international ImMunoGeneTics database, freely available at http://imgt.cines.fr:8104, was created in 1989 at the Université Montpellier II, CNRS, Montpellier, France, and is a high quality integrated information system specialising in immunoglobulins, T cell receptors and major histocompatibility complex molecules of human and other vertebrates. IMGT provides researchers and clinicians with a common access to all nucleotide, protein, genetic and structural immunogenetics data. This information is of high value for medical and veterinary research, biotechnology related to antibody and T cell receptor engineering, genome diversity and evolution studies of the immune response.     

IMGT, the International ImMunoGeneTics database.

IMGT, the international ImMunoGeneTics database, is an integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) of all vertebrate species, created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes three databases: LIGM-DB (for Ig and TcR), MHC/HLA-DB and PRIMER-DB (the last two in development). IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 23 000 Immunoglobulin and T cell Receptor sequences from 78 species. MHC/HLA-DB contains Class I and Class II Human Leucocyte Antigen alignment tables. An IMGT tool, DNAPLOT, developed for Ig, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including nucleotide and protein sequences, oligonucleotide primers, gene maps and other genetic data of Ig, TcR and MHC molecules, and to provide a graphical user friendly data access. IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc.fr:8104     

IMGT standardization for statistical analyses of T cell receptor junctions: the TRAV-TRAJ example

The diversity of immunoglobulin (IG) and T cell receptor (TR) chains depends on several mechanisms: combinatorial diversity, which is a consequence of the number of V, D and J genes and the N-REGION diversity, which creates an extensive and clonal somatic diversity at the V-J and V-D-J junctions. For the IG, the diversity is further increased by somatic hypermutations. The number of different junctions per chain and per individual is estimated to be 10(12). We have chosen the human TRAV-TRAJ junctions as an example in order to characterize the required criteria for a standardized analysis of the IG and TR V-J and V-D-J junctions, based on the IMGT-ONTOLOGY concepts, and to serve as a first IMGT junction reference set (IMGT, http://imgt.cines.fr). We performed a thorough statistical analysis of 212 human rearranged TRAV-TRAJ sequences, which were aligned and analysed by the integrated IMGT/V-QUEST software, which includes IMGT/JunctionAnalysis, then manually expert-verified. Furthermore, we compared these 212 sequences with 37 other human TRAV-TRAJ junction sequences for which some particularities (potential sequence polymorphisms, sequencing errors, etc.) did not allow IMGT/JunctionAnalysis to provide the correct biological results, according to expert verification. Using statistical learning, we constructed an automatic warning system to predict if new, automatically analysed TRAV-TRAJ sequences should be manually re-checked. We estimated the robustness of this automatic warning system.     

IMGT, a system and an ontology that bridge biological and computational spheres in bioinformatics

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), is the reference in immunogenetics and immunoinformatics. IMGT standardizes and manages the complex immunogenetic data that include the immunoglobulins (IG) or antibodies, the T cell receptors (TR), the major histocompatibility complex (MHC) and the related proteins of the immune system (RPI), which belong to the immunoglobulin superfamily (IgSF) and the MHC superfamily (MhcSF). The accuracy and consistency of IMGT data and the coherence between the different IMGT components (databases, tools and Web resources) are based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets relying on seven axioms, 'IDENTIFICATION', 'DESCRIPTION', 'CLASSIFICATION', 'NUMEROTATION', 'LOCALIZATION', 'ORIENTATION' and 'OBTENTION', that postulate that objects, processes and relations have to be identified, described, classified, numerotated, localized, orientated, and that the way they are obtained has to be determined. These axioms constitute the Formal IMGT-ONTOLOGY, also designated as IMGT-Kaleidoscope. These axioms have been essential for the conceptualization of the molecular immunogenetics knowledge and for the creation of IMGT. Indeed all the components of the IMGT integrated system have been developed, based on standardized concepts and relations, thus allowing IMGT to bridge biological and computational spheres in bioinformatics. The same axioms can be used to generate concepts for multi-scale level approaches at the molecule, cell, tissue, organ, organism or population level, emphasizing the generalization of the application domain. In that way the Formal IMGT-ONTOLOGY represents a paradigm for the elaboration of ontologies in system biology.     

IMGT-Kaleidoscope, the formal IMGT-ONTOLOGY paradigm

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), is the reference in immunogenetics and immunoinformatics. IMGT standardizes and manages the complex immunogenetic data which include the immunoglobulins (IG) or antibodies, the T cell receptors (TR), the major histocompatibility complex (MHC) and the related proteins of the immune system (RPI) which belong to the immunoglobulin superfamily (IgSF) and the MHC superfamily (MhcSF). The accuracy and consistency of IMGT data and the coherence between the different IMGT components (databases, tools and Web resources) are based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets relying on seven axioms, "IDENTIFICATION", "DESCRIPTION", "CLASSIFICATION", "NUMEROTATION", "LOCALIZATION", "ORIENTATION" and "OBTENTION", that postulate that objects, processes and relations have to be identified, described, classified, numerotated, localized, orientated, and that the way they are obtained has to be determined. These axioms constitute the Formal IMGT-ONTOLOGY, also designated as IMGT-Kaleidoscope. Through the example of the IG molecular synthesis, the concepts generated from the "IDENTIFICATION", "DESCRIPTION", "CLASSIFICATION" and "NUMEROTATION" axioms are detailed with their main instances and semantic relations. The axioms have been essential for the conceptualization of the molecular immunogenetics knowledge and can be used to generate concepts for multi scale approaches at the molecule, cell, tissue, organ, organism or population level, emphasizing the generalization of the application domain. In that way the Formal IMGT-ONTOLOGY represents a paradigm for the elaboration of ontologies in system biology.     

IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex

The IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla) has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System for the past four years. Since its initial release the database has grown and is the primary source of information for the study of sequences of the human major histocompatibilty complex. The initial release of the database contained a limited number of tools. As a result of feedback from our users and developments in HLA we have been able to provide new tools and facilities. The HLA sequences have also been extended to include intron sequences and the 3' and 5' untranslated regions in the alignments and also the inclusion of new genes such as MICA. The IMGT/MHC database (http://www.ebi.ac.uk/imgt/mhc) was released in March 2002 to provide a similar resource for other species. The first release of IMGT/MHC contains the sequences of non-human primates (apes, new and old world monkeys), canines and feline sequences. Further species will be added shortly and the database aims to become the primary source of MHC data for non-human sequences.     

IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties

IMGT, the international ImMunoGeneTics information system(R) (http://imgt.cines.fr) is a high-quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. IMGT comprises IMGT/LIGM-DB, the comprehensive database of IG and TR sequences from human and other vertebrates (76 846 sequences in September 2003). In order to define the IMGT criteria necessary for standardized statistical analyses, the sequences of the IG variable regions (V-REGIONs) from productively rearranged human IG heavy (IGH) and IG light kappa (IGK) and lambda (IGL) chains were extracted from IMGT/LIGM-DB. The framework amino acid positions of 2474 V-REGIONs (1360 IGHV, 585 IGKV, 529 IGLV) were numbered according to the IMGT unique numbering. Two statistical methods (correspondence analysis and hierarchic classification) were used to analyze the 237 framework positions (80 for IGHV, 79 for IGKV, 78 for IGLV), for three properties (hydropathy, volume and chemical characteristics) of the 20 common amino acids. Results of the analyses are shown as standardized two-dimensional representations, designated as IMGT Colliers de Perles statistical profiles. They provide a characterization of the amino acid properties at each framework position of the expressed IG V-REGIONs, and a visualization of the resemblances and differences between heavy and light, and between kappa and lambda sequences. The standardized criteria defined in this paper, amino acid positions and property classes, will be useful to study the mutations and allele polymorphisms, to establish correlations between amino acids in the IG and TR protein three-dimensional structures and to extract new knowledge from V-like domains of chains, other than IG and TR, belonging to the immunoglobulin superfamily.     

IMGT/HighV-QUEST: the IMGT® web portal for immunoglobulin (IG) or antibody and T cell receptor (TR) analysis from NGS high throughput and deep sequencing

Background: The number of antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR) of the adaptive immune response in vertebrates with jaws is almost unlimited (2.1012 per individual in humans). IMGT®, the international ImMunoGeneTics information system®, has developed online tools that provide a detailed and accurate sequence analysis of the V domains (IMGT/V-QUEST) and CDR3 (IMGT/JunctionAnalysis), based on IMGT-ONTOLOGY. However online analyses are limited to 50 sequences per batch. The challenge was to provide identical high quality analysis for the huge number of sequences obtained by Next Generation Sequencing (NGS) high throughput and deep sequencing.Results: IMGT® has developed IMGT/HighV-QUEST that analyses up to 150,000 IG or TR V domain sequences per batch and performs statistical analysis on the results of up to 450,000 sequences. IMGT/HighV-QUEST provides users with: (i) a friendly web interface for submission and results retrieval, (ii) high quality detailed results of IMGT/V-QUEST and IMGT/JunctionAnalysis, based on the IMGT-ONTOLOGY concepts and IMGT Scientific chart rules, (iii) a standardized frame for NGS statistical analysis, based on ‘Results category’ (‘1 copy’, ‘More than 1’, ‘single allele’, ‘several alleles (or genes)’, (iv) detailed standardized statistical analysis tables and histograms (e.g., V, D and J usage, CDR3-IMGT lengths).Conclusions: IMGT/HighV-QUEST has been freely available for use for academics on the IMGT® Home page (http://www.imgt.org) since October 2010. More than 123 million sequences were submitted during its first year. IMGT/HighV-QUEST is a key component for establishing reliable repertoires of IG and TR V domains. These repertoires will contribute to the individual immunoprofiles in diverse immune situations and on different B and T cell populations. They will also contribute to characterize potential therapeutic antibodies from combinatorial libraries.