IMGT-ONTOLOGY and IMGT databases, tools and Web resources for immunoinformatics

Transcription

1 IMGT-ONTOLOGY and IMGT databases, tools and Web resources for immunoinformatics Marie-Paule Lefranc Université Montpellier, CNRS First international Immunoinformatics Symposium Yokohama, Japan, February 2004 RIKEN Yokohama Institute The international ImMunoGeneTics information system Coordinator: M.-P. Lefranc, Montpellier, France

2 IMGT domain of research: the adaptive immune system Vertebrates Immunoglobulin peptide T cell B cell T cell Receptor MHC Trimolecular complex The international ImMunoGeneTics information system Coordinator: M.-P. Lefranc, Montpellier, France

3 Immunoglobulin (IG) and T cell receptor (TR) synthesis 150 FUNCTIONAL IG GENES HEAVY CHAIN V D J C 5' 3' V J C 5' 3' LIGHT CHAIN x 2 3 x x 5 Kappa x 4-5 Lambda 6300 POTENTIAL RECOMBINATIONS POTENTIAL RECOMBINATIONS N-DIVERSITY SOMATIC MUTATIONS x ' 3' 5' 3' ABOUT 6.3 x 10 6 POSSIBILITIES ABOUT 3.5 x 10 5 POSSIBILITIES 2 x DIFFERENT ANTIBODIES

4 IMGT-ONTOLOGY IMGT-ONTOLOGY five main concepts to share, reuse and represent knowledge in immunogenetics IDENTIFICATION OBTENTION CLASSIFICATION NUMEROTATION DESCRIPTION

5 "IDENTIFICATION" concept Species Receptor human mouse.. Molecule type genomic DNA cdna protein.. Gene variable diversity joining constant Configuration germline rearranged Chain type Ig-Heavy Ig-Light-Lambda TcR-Alpha TcR-Beta... Structure type regular translocated... IgA TcR gamma-delta Specificity Anti-DNA Anti-HIV... Functionality functional ORF pseudogene productive unproductive

6 "CLASSIFICATION" concept group is a member of an instance of locus IGLV is a member of human IGL (22q11.2) subgroup is a member of an instance of is ordered in an instance of IGLV2 is a member of is ordered in gene IGLV2-11 is a variant of an instance of is a variant of allele IGLV2-11*02

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10 "DESCRIPTION" concept L-PART1 V-GENE V-EXON 5 UTR FR1-IMGT FR2-IMGT FR3-IMGT C W C CDR3 -IMGT 3 UTR DONOR-SPLICE V-REGION Label 1 Label 2 V-GENE V-EXON Relations entre Labels FR3-IMGT L-PART1 V-REGION V-REGION CDR3-IMGT DONOR-SPLICE FR1-IMGT CDR3-IMGT

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12 "NUMEROTATION" concept Collier de Perles Alignment of alleles Protein Display

13 IMGT Collier de Perles

14 V-DOMAIN 3D representation (TR A6, 1ao7)

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16 IMGT-ML schema IMGTOntology Identification Classification Obtention Description Numerotation imgt knowledge seqdata External schema External schema IMGTData

17 IMGT-ML architecture Information system modelling IMGT-ONTOLOGY Biological expertise Biological expertise XML schema XML schema Data Data distribution format format Documentation Controlled vocabulary

18 Informatic answers to the biological problems Use IMGT-ONTOLOGY (and IMGT-ML) Allow IMGT components to dynamically interact The Web Services Dynamic interactions IMGT/LIGM-DB IMGT/V-QUEST Web Service IMGT/LIGM-DB Sequences Gene names + ref. seq. Web Service IMGT/V-QUEST

19 Example of IMGT/V-QUEST results V-GENE JUNCTION J-GENE

20 Diagram of collaboration: Analyse de repertoires Web Service IMGT/LIGM-DB DYNAMIC INTERACTIONS Web Service IMGT/V-QUEST DYNAMIC INTERACTIONS Sequences with specificity Web Service IMGT/GENE-DB DYNAMIC INTERACTIONS Web Service IMGT/LocusView Gene localization Web Service IMGT/GeneFrequency

21 Example of IMGT/GeneFrequency results

22 Diagram of collaboration: Analyse des jonctions Web Service IMGT/LIGM-DB DYNAMIC INTERACTIONS Web Service IMGT/V-QUEST DYNAMIC INTERACTIONS Web Service IMGT/GENE-DB Gene and allele names Web Service IMGT/JunctionAnalysis

23 Example of IMGT/JunctionAnalysis results

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25 IMGT-Choreography: Expressed IG and TR repertoires

26 IMGT-Choreography: 3D structures/specificities V-D-J-JUNCTION V-J-JUNCTION Side view View from above the CDRs V-DOMAINs (Mus musculus E5.2 Fv)

27 "OBTENTION" concept cell, tissue, organ - PBL - liver autoimmune diseases - autoantibody - rheumatoid factor clonal expansion diseases -leukemia - lymphoma -myeloma PCR hybridoma - monoclonal antibody transgenic -animal -plant libraries - genomic - cdna -combinatorial origin methodology

28 Immunoinformatics Data integration specific to Immunology Gene Transcript Bioinformatics databases,and tools *interactions host-pathogens *vaccinology *immunomodulation Protein Microarrays 3D Organelle Cell Collection of clinical data Gene regulation Pathways Networks Population Tissue Organism Organ Mathematical and computational models

29 Who is using IMGT? Medical research: repertoire in autoimmune diseases, AIDS, leukemias, lymphomas, myelomas, translocations, detection of residual diseases Veterinary research: IG and TR repertoire of domestic and farm species Genome diversity: comparative and developmental immunology, evolution of the adaptive immune system Therapeutic approaches: immunotherapy, grafts, immunomodulation, immunosuppression Biotechnology related to antibody engineering: chimeric, humanized, human antibodies, scfv, combinatorial libraries, intrabodies

30 IMGT, the international ImMunoGeneTics information system The IMGT team at Montpellier, France