Bioinformatics Montpellier Genopole Journes Bioinformatique des Gnopoles Lyon

Bioinformatics Montpellier Genopole Journées "Bioinformatique des Génopoles" Lyon, 22 -23 octobre 2003 Committee : L. Chiche (CBS), O. Gascuel (LIRMM), M. -P. Lefranc (IGH) And : CIRAD, CRBM, GPI, IBP, IGMM, ISEM, LDCC Montpellier has an high research potential in Bioinformatics: § More than 50 researchers, Ph. Ds and post-doctoral students § Internationally recognized programs, databases and servers: PHYLOWIN, IMGT, ESTHER, DOMO, BIOSERV, STAR … BIONJ, § National and international responsibilities, e. g. Chair of ACI IMPBio. Thanks to the Genopole: § 10 within Genopole collaborations supported by French programs § A master (DESS) in Bioinformatics § Bioinformatics seminars (2/month) and events (eg, Transcriptome Statistical Analysis, 110 attendees, 2002).

Bioinformatics Montpellier Genopole Three main axes § IMGT § Structural Bioinformatics (protein structure prediction, structural domain clustering, NMR spectra analysis, Knottin database) § Comparative genomics (phylogeny, sequence analysis, alignment) Perspectives: § Developing IMGT and structural servers and databases § Spreading our software § Designing new dedicated servers (e. g. , transcriptome interpretation) § Providing courses on software § Incentive policy towards “young teams”

IMGT, the international reference in Immunogenetics and Immunoinformatics IMGT, a common access to standardized, expertly annotated and integrated data IMGT, IMGT specialized in an European flagship Immunoglobulins (IG) (antibodies) (BIOMED 1, BIOTECH, 5 th PCRDT) IMGT, the international Im. Muno. Gene. Tics information system ® http: //imgt. cines. fr Coordinator: Marie-Paule LEFRANC IMGT, a CNRS registered trademark T cell receptors (TR) Major histocompatibility complex (MHC) IMGT, unique EU, Canada, USA No equivalent in Japan and in USA RIO Platform 2001 Net. Watch of Science 2002

IMGT domain of research: the adaptive immune system Immunoglobulin peptide T cell B cell T cell Receptor MHC Trimolecular complex The international Im. Muno. Gene. Tics information system® Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

Immunoglobulin and T cell receptor synthesis 25 0 FUNCTIONAL GENES HEAVY CHAIN V D J LIGHT CHAIN C V 5' 3' J C 3' 5' 39 - 4 6 x 2 3 x 6 34 - 37 30 - 3 3 x x 5 4 -5 Kappa Lambda 185 +165 POTENTIAL RECOMBINATIONS 6300 POTENTIAL RECOMBINATIONS N REGIONS AND SOMATIC MUTATIONS 5' ABOUT 3' x 1000 5' 3' ABOUT 3. 5 x 10 5 POSSIBILITIES 6. 3 x 10 6 POSSIBILITIES 2 x 10 12 DIFFERENT ANTIBODIES The international Im. Muno. Gene. Tics information system® Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

5 Databases 8 Tools on line Web Resources 8000 HTML pages! Sequence databases Sequence analysis Sequences IMGT/LIGM-DB 77, 463 IG • IMGT/V-QUEST Alignments of alleles • IMGT/Junction. Analysis Tables of alleles and TR nucleotide sequences from human and 150 other vertebrate species, on the Web since July 1995 IMGT/PRIMER-DB on the Web since 2000 • IMGT/Phylo. Gene Protein displays, etc. IMGT Repertoire IMGT/MHC-DB hosted at EBI • IMGT/Allele-Align Genome database Genome analysis Genome IMGT/GENE-DB • IMGT/Gene. Search • IMGT/Gene. View • IMGT/Locus. View Chromosomal localizations Locus representations Gene tables, etc. 3 D structure analysis • IMGT/Structural. Query 2 D and 3 D structures 1375 IG and TR genes and 2201 alleles from human and mouse, on the Web since February 2003 3 Dstructure database IMGT/3 Dstructure-DB 634 structures of IG, TR and MHC 2 D Colliers de Perles 3 D representations, etc. http: //imgt. cines. fr

IMGT-ONTOLOGY http: //imgt. cines. fr IMGT-ONTOLOGY has been developed to share, reuse and represent knowledge in immunogenetics IMGT-ONTOLOGY covers five main concepts: IDENTIFICATION OBTENTION CLASSIFICATION NUMEROTATION DESCRIPTION

"CLASSIFICATION" concept http: //imgt. cines. fr A group locus is a member of an instance of subgroup is a member of an instance of gene is a variant of an instance of allele IGLV human IGL (22 q 11. 1 -q 11. 2) B is a member of is ordered in an instance of IGLV 2 is ordered in is a member of IGLV 2 -11 is a variant of IGLV 2 -11*02 The "CLASSIFICATION" concept organizes the immunogenetics knowledge useful to name and classify IG and TR genes in IMGT. (A) Concepts of classification and their relations. (B) Examples of instances: for each concept of classification is shown the instance which allows the classification of the human IGLV 2 -11*02 allele.

The international Im. Muno. Gene. Tics database Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

"DESCRIPTION" concept V-GENE L-PART 1 V-EXON FR 2 -IMGT C DONOR-SPLICE Label 1 Label 2 V-GENE V-EXON FR 3 -IMGT CDR 3 -IMGT L-PART 1 DONOR-SPLICE V-REGION FR 1 -IMGT V-REGION CDR 3 -IMGT W FR 3 -IMGT C CDR 3 -IMGT FR 1 -IMGT 5 ’UTR 3 ’UTR V-REGION Label relations The international Im. Muno. Gene. Tics information system® Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

http: //imgt. cines. fr

"NUMEROTATION" concept http: //imgt. cines. fr Collier de Perles Protein Display Alignment of alleles

http: //imgt. cines. fr

Collier de Perles:

3 D representation: Human V-DOMAINS from Tc. R ab A 6 (PDB: 1 ao 7 )

"OBTENTION" concept cell, tissue, organ - PBL - liver transgenic - animal - plant libraries - genomic - c. DNA -combinatorial autoimmune diseases - autoantibody - rheumatoid factor clonal expansion diseases - leukemia - lymphoma - myeloma origin PCR hybridoma - monoclonal antibody methodology The "OBTENTION" concept specifies the origin and methodology http: //imgt. cines. fr

IMGT-ML Schema imgt IMGTOntology Identification IMGTData knowledge Classification seq. Data Obtention Description Numerotation External schema http: //imgt. cines. fr

IMGT-ML Architecture http: //imgt. cines. fr Database modelling IMGT-ONTOLOGY XML Schema Biological expertize Data distribution format Controlled vocabulary Documentation

IMGT Platform 2000 -2003 1. Research and development 52 publications 1 chapter "Consanguinity" in Encyclopedia of Genetics 2001 2 books: The Immunoglobulin Facts. Book, Academic Press, 2001 The T cell receptor Facts. Book, Academic Press, 2001 47 communications 27 invited conferences (China, Japan, USA, Belgium, Italia, The Netherlands, UK) 2 Ph. D theses (1 tenure job at CIRAD, 1 postdoctorate at Princeton, USA) collaborations USA, Canada, China, Russia, Lebanon, UK, Belgium (EUROGENTEC) 2. Services • WWW at Montpellier: 180, 000 sites since January 2000 140, 000 requests per month • Data distribution by FTP: CINES, IGH, INFOBIOGEN, EBI • Many sites SRS: INFOBIOGEN, EBI, Institut Pasteur, . . . and EMBnet nods • Search by BLAST and FASTA: on different servers (INFOBIOGEN, EBI, etc. ) • IMGT Bloc-notes: IMGT Immunoinformatics page, numerous hyperlinks to external sites The international Im. Muno. Gene. Tics information system® Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

IMGT platform 3. Education Participation to the creation of the: • DESS Bioinformatics: Université Montpellier II, 2001 • Bioinformatics modules: Doctoral School CBS 2, Montpellier, 2001 Doctoral School Univ. St-Joseph, Beirut, Lebanon, 2002 University of Monastir, Tunisia, 2003 4. Innovations, normes et standards IMGT-ONTOLOGY, the first and only ontology in immunogenetics and immunoinformatics. IMGT Scientific chart provides the controlled vocabulary and the annotation rules • IMGT nomenclature approved by the Human Genome Organization (HUGO) Nomenclature Committee (HGNC) in 1999, 673 human genes and 1206 alleles. The only example of delegation by HGNC. • direct links from Locus. Link NCBI to IMGT. The only example of direct links from NCBI to an external site • In development: XML and IMGT-ML, Web-Services, Data integration in medical informatics. The international Im. Muno. Gene. Tics information system® Coordinator: M. -P. Lefranc, Montpellier, France http: //imgt. cines. fr

Genome diversity developmental and comparative immunology, evolution of the adaptive immune system Medical research repertoire in normal and pathological situations, autoimmune diseases, AIDS, leukemias, lymphomas, myelomas, residual diseases, etc. IMGT, a team of 21 persons: Veterinary research 8 CDD annotators repertoire in farm and wild animal species (5 EU, 1 EUROGENTEC 1 Genopole, 1 PPF) 4 Permanent staff IMGT, the international Im. Muno. Gene. Tics information system® http: //imgt. cines. fr Coordinator : Marie-Paule LEFRANC (UM 2: 1. 5 PU, 0. 5 IE CNRS: 1 IE, 1 ITA) Therapeutical approaches 9 Students (3 Ph. D, immunotherapy, grafts, immunomodulation, immunosppression 6 for 4 months/a year) Biotechnology and antibody engineering chimeric, humanized, human antibodies in transgenic mice, sc. Fv combina torial libraries, intrabodies