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Marseille-Nice Genopole

Marseille-Nice Genopole. A consortium to accelerate the applications of high-throughput genome analysis,functional genomics in Immunology, Developmental Biology, Microbiology & Human Pathology. Denis THIEFFRY & Richard CHRISTEN. Scientific Actions. 1. Bioinformatics

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Marseille-Nice Genopole

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  1. Marseille-Nice Genopole A consortium to accelerate the applications of high-throughput genome analysis,functional genomics in Immunology, Developmental Biology, Microbiology&Human Pathology Denis THIEFFRY & Richard CHRISTEN

  2. Scientific Actions 1. Bioinformatics 2. Transcriptome studies 3 Functional exploration in vertebrates 4 Functional exploration in non-vertebrates 5. Genome variations 6. Cancer genomics 7. Microbial sequencing 8. Structural genomics 9. Proteomics 1O. Teaching of bioinformatics

  3. Bioinformatics Aim: Developing inter-disciplinary research in relation with genomics, transcriptomics & proteomics Strategy and instruments:-Bi-monthly interdisciplinary seminars + summer schools and workshops-Development of a teaching platform dedicated to computational biology (Marseille + Nice)

  4. Bioinformatics Teaching Plateform Dedicated teaching rooms eachwith 20 terminals (Marseille + Nice) Powerful dedicated serverswith main molecular databases and bioinformatic suites (EMBOSS, SRS, BLAST...) Development of computational biology curricula: Licence, DESS, DEA, Engineering degrees, Research and Professional Masters, Doctorate

  5. Bioinformatics: Main Research Areas Transcriptome: integration and analysis of expression data; DNA array conception Pattern discovery and search in nucleic acid sequences Integration and modelling of functional macromolecular system data; microbial genome annotation; databases Computational analysis of genetic regulatory networks Phylogeny

  6. Bioinformatics Research: Main laboratories BioMath/Phys Info

  7. Bioinformatics: Stimulation of Interdisciplinary Research BioMath/Phys Info

  8. CDD in Bioinformatics • Dispatching of Bioinformatics CDD in support of the transcriptome and proteome platforms • Jean Fred FONTAINE (1/4/2002-31/08/2002) - Marseille (5 months)Development of a JAVA environment to process transcriptome data (normalisation, statistical analysis, classification...): interface; evolution toward a distributed scheme (CORBA). • Pierre Fabrice LOPEZ (1/11/2002-30/4/2002) - Marseille (6 months)Development of a Java software for the automatic quantification of microarray data (Bzscan). Development of statistical tools for the normalisation and the analysis of DNA array data (Genesys), using statistical function of R and the distributed architecture CORBA. Data in the format XML with a complete compatibility with MIAME recommendations. • David BOURGAIS (01/05/03-31/10/03) - Marseille (6 months)Integration data analysis software (ex: SEAQUEST) for the proteomics platform of Marseille. • Kevin Le Brigand (01/05/2003-26/05/2004) - Nice (12 months)Development of the MEDIANTE application at Sophia Antipolis.

  9. Bioinformatics Research:Microbial genome annotation Complete genome sequence & annotation of a nannobacterium Ramlibacter tataouinensis Ramlibacter tataouinensis TTB310 Ramlibacter tataouinensis TTB310 Ramlibacter tataouinensis TTB310 LEMiR/ UMR 163 CNRS-CEA, Cadarache LBV Nice Heulin et al. (2003). Int J Syst Evol Microbiol53: 589-594. Sandy soil bacteria ( Tataouine , Tunisia ) • Birth Jan. Presents two morphotypes with unequivalent properties • 1999 200 nm Rod - shaped cell ( Æ 2 00 nm) ( peripheral differen - tiation on agar) Differentiation Motile signal ? Motile rod Differentiation Cyst signal ? Cellular Division 200 nm Dessiccation Resistance Cyst - like cell Æ ( 800 nm)

  10. Bioinformatics Research:Microbial genome annotation Complete genome sequence & annotation of Ramlibacter tataouinensis Genome project FXOA genoscope (grants from CNRS, MESR, CEA) Preparation Dec . Sept. genome size estimation by Pulse Field Gel Electrophoresis (4 Mb) 2002 search for financial support Cloning Sept. purified DNA ( phenol / chloroform ) sent to the GENOSCOPE Dec . 2002 Construction of four plasmidic banks Dec . "Pairwise" sequencing Apr . around 35,000 clones sequenced 2003 Sequences assembly Apr . June from 52,000 to 70,000 sequences assembled 2003 June Finishing , ..., final assembly Dec . design of primers and sequencing of the gaps, final assembly 2003 Dec . Jan. Beginning of the annotation 2004

  11. Bioinformatics Research:Transcriptome Using a knowledge database for cluster annotation

  12. Bioinformatics Research:Transcriptome Automatic annotation of internal nodes

  13. Bioinformatics Research: Transcriptome Zoom in and get all known evidences

  14. Bioinformatics Research:Transcriptome An exemple using Flybase ontology thorax vs head thorax vs whole body Head vs whole body

  15. Bioinformatics Research:Transcriptome Co-localisation and co-expression ?

  16. Bioinformatics Research:Transcriptome Co-localisation and co-expression ? Ch IV Ch I

  17. RNAMaturation Cellular Polarity Cytokinesis DNA Synthesis Nucleo-cytoplasmicTransport BioinformaticsResearch:Molecular Networks ProDistIn: functional classification and prediction using graph-based distances 600 Yeast proteins (over 2100 proteins and 4500 interactions)  29 cellular roles(according to YPD annotations) Brun et al. (2003). J Struct Funct Genomics3: 213-24. BioMath/Phys Info

  18. BioinformaticsResearch: Molecular Networks GIN-sim: Qualitative dynamical modelling, analysis and simulation of genetic regulatory networks (1) Java classes GRAPH ANALYSER SIMULATION MODULE USER INTERFACE Dynamical graph Regulatory graph Model refinements Chaouiya et al. (2003). Lect Notes Control Info Sci294: 119-126. Remy et al. (2003) Bioinformatics19 Suppl 2:ii172-8. Sánchez & Thieffry (2003). J theor Biol224: 517-37. Thieffry & Sánchez (2002). Ann N Y Acad Sci. 981: 135-53.

  19. BioinformaticsResearch:Molecular Networks GIN-sim: Qualitative dynamical modelling, analysis and simulation of genetic regulatory networks (2)

  20. BioinformaticsResearch:Molecular Networks GIN-sim: Qualitative dynamical modelling, analysis and simulation of genetic regulatory networks (3)

  21. BioinformaticsResearch: Molecular Networks GIN-sim: Qualitative dynamical modelling, analysis and simulation of genetic regulatory networks (4)

  22. BioinformaticsResearch: Molecular Networks GINML: Gene-Interaction Network Modelling Language http://www.esil.univ-mrs.fr/~chaouiya/Recherche/GINML/

  23. Bioinformatics Research: Nucleic Patterns Annotation of RNA genes and RNA motifs Gautheret & Lambert (2001). J Mol Biol 313(5): 1003-11. Lambert et al. (2002). Biochimie84(9): 953-9 Legendre & Gautheret (2003). BMC Genomics 4(1): 7. Based on the Erpin program, a central resource for non-coding RNA annotation: tagc.univ-mrs.fr/erpin

  24. Bioinformatics Research:Phylogenomics Evidence of en bloc duplication in vertebrate genomes Abi-Rached et al. (2002).Nat Genet31(1): 100-5. Phylogenix start-up : Development of a genome annotation plate-form using phylogenetic information

  25. Bioinformatics Research:Phylogenomics Evidence of en bloc duplication in primate genomes Courseaux et al. (2003 ) Genome Res13: 369-81. Courseaux & Nahon (2001 ). Science291: 1293-7.

  26. Analysis Software ABCAvailable Novembre 2003 (moving to new site)Object: Data mining of DNA chip data using Knowledge databases (ontologies)Link w/Genopole: transcriptome analysis BZSCANhttp://tagc.univ-mrs.frObject: Automatic quantification of DNA microarray imagesLink w/Genopole: transcriptome analysis and cancerology Erpinhttp://tagc.univ-mrs.fr/pub/erpin/Object: homology-based non-coding RNA identificationLink w/ Genopole: Developed through collaboration between TAGC & CPT ESTAhttp://ir2lcb.cnrs-mrs.frObject: Search for proteins coding regions in organisms poorly represented in databases Link w/ Genopole: Developed by LCB ESTparserhttp://tagc.univ-mrs.fr/bioinfo/ESTparser/Object: Annotation/analysis of polyadenylation sites in human genesLink w/Genopole: Transcriptome analysis FSEDhttp://ir2lcb.cnrs-mrs.frObject: Search for sequencing errors due to changes in reading framesLink w/ Genopole: Developed by LCB GelPrinthttp://igs-server.cnrs-mrs.fr/Object: Display of proteomic dataLink w/ Genopole: Developed at the IGS GeneANOVAAvailable on request to didier@genopole.cnrs.frObject: ANOVA-based software devoted to the analysis of gene expression dataLink w/Genopole: collaboration with Evry Genopole GIN-simSoon available at http://gin.univ-mrs.frObject: Qualitative dynamical simulation of molecular and genetic regulatory networksLink w/Genopole: developed at the LGPD in collaboration with the IML and the LIF QualipartAvailable on request to guenoche@iml.univ-mrs.frObject: Evaluation of the quality of a partitionLink w/ Genopole: Developed through collaboration between IML and LIF QualitreeAvailable on request to guenoche@iml.univ-mrs.frObject: Evaluation of the quality of a treeLink w/ Genopole: Developed through collaboration between IML and LIF RECTSAhttp://ir2lcb.cnrs-mrs.fr/Object: search for coding and non coding regions in large genome regionsLink w/ Genopole: Developed by LCB PhydBachttp://igs-server.cnrs-mrs.fr/Object: Functional predictionLink w/ Genopole: Developed at the IGS RNAmotifhttp://www.scripps.edu/case/casegr-sh-2.5.htmlObject: descriptor-based non-coding RNA identificationLink w/ Genopole: none. Collaboration with US groups. SATPhttp://igs-server.cnrs-mrs.fr/Object: Statistical analysis of transcription profilesLink w/ Genopole: Developed at the IGS SamBahttp://igs-server.cnrs-mrs.fr/Object: Optimal design of large experiments using incomplete factorial analysisLink w/ Genopole: Developed at the IGS SelfIDhttp://igs-server.cnrs-mrs.fr/Object: Automated bacterial gene finderLink w/Genopole: developed at the IGS SequamAvailable Novembre 2003 (moving to new site)Object: Design of primers and probesLink w/Genopole: bioinformatics for microbiology. Tcoffeehttp://igs-server.cnrs-mrs.fr/Tcoffee/Object: A Tool For Multiple Sequence AlignmentsLink w/ Genopole: Developed at the IGS

  27. Databases ABCdbhttp://ir2lcb.cnrs-mrs.fr/ABCdb/Object: a database for the identification and reconstruction of ABC transporters in completely sequenced bacterial genomesLink w/Genopole: collaboration between LCB and ARC ALLONTO.dbAvailable Novembre 2003 (moving to new site)Object: Ontologies for transcriptome analysisLink w/Genopole: transcriptome analysis BIGShttp://igs-server.cnrs-mrs.fr/ Object: Database of the targets of IGS structural genomics, node of the world-wide TargetDB networkLink w/Genopole: developed at the IGS CAZyhttp://afmb.cnrs-mrs.fr/CAZY/Object: Description of the families of structurally-related carbohydrate-binding modules of enzymes that degrade, modify, or create glycosidic bondsLink w/Genopole: developed at the AFMB FusionDBhttp://igs-server.cnrs-mrs.fr/FusionDB/Object: database of bacterial and archaeal gene fusion events - also known as Rosetta stonesLink w/Genopole: developed at the IGS GIN-dbSoon available at http://gin.univ-mrs.frObject: Interaction of molecular and genetic interaction and regulatory dataLink w/Genopole: developed at the LGPD in collaboration with the LIF Pa2Cdbhttp://ir2lcb.cnrs-mrs.fr/ABCdb/Object: a database for the identification and reconstruction of two component systems in Pseudomonas aeruginosaLink w/Genopole: developed by LCB RICBASEhttp://igs-server.cnrs-mrs.fr/Object: Rickettsia comparative genomics databaseLink w/Genopole: developed at the IGS rRNA.db Available on request. On the web early 2004Object: 100 000 rRNA and ITS sequences, aligned and analyzed by phylogeny, for phylogeny and DNA chip conception.Link w/Genopole: bioinformatics for microbiology. Tropheryma whipplei genome databasehttp://igs-server.cnrs-mrs.fr/mgdb/Tropheryma/Link w/Genopole: developed at the IGS

  28. Selected Publications Beaudoing E, Gautheret D. (2001). Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data. Genome Res 9: 1520-26. Brazma A, Hingamp P et al (2001) Minimum Information About a Microarray Experiment - MIAME - towards Standards for Microarray Data. Nature Genet 4: 365-71. Brun C, Guenoche A, Jacq B (2003). Approach of the functional evolution of duplicated genes in Saccharomyces cerevisiae using a new classification method based on protein-protein interaction data. J Struct Funct Genomics 3: 213-24. Remy E, Mosse B, Chaouiya C, Thieffry D (2003). Discrete dynamics of regulatory feedback circuits. Bioinformatics 19 (supp 2): ii172-8. Claverie JM, Raoult D (2001). Mechanisms of evolution in Rickettsia conorii and R. prowazekii. Science 293: 2093-8. Claverie JM, Ogata H (2003). The insertion of palindromic repeats in the evolution of proteins. Trends Biochem Sci 28: 75-80. Daborn PJ, Yen L, Bogwitz M, LeGoff G, Feil E, Jeffers S, Tijet N, Perry T, Heckel D, Batterham P, Feyereisen R, Wilson T, ffrench-Constant RH (2002). A single P450 allele associated with insecticide resistance in Drosophila. Science 297: 2253-6. Gautheret D, Lambert A (2001). Direct RNA definition and identification from multiple sequence alignments using secondary structure profiles. J Mol Biol 313: 1003-11. Henrissat B, Coutinho PM. (2001) Classification of glycoside hydrolases and glycosyltransferases from hyperthermophiles. Methods Enzymol330: 183-201 Henrissat B, Coutinho PM, Davies GJ. (2001) A census of carbohydrate-active enzymes in the genome of Arabidopsis thaliana. Plant Mol Biol47: 55-72 Henrissat B, Deleury E, Coutinho PM. (2002) Glycogen metabolism loss: a common marker of parasitic behaviour in bacteria? Trends Genet18: 437-40 Legendre M, Gautheret D (2003). Sequence determinants in human polyadenylation site selection. BMC Genomics 4: 7. Lescure A, Gautheret D, Krol A (2002). Novel selenoproteins identified from genomic sequence data. Methods Enzymol 347: 57-70. Megy K, Audic S, Claverie JM (2003). Positional clustering of differentially expressed genes on human chromosomes 20, 21 and 22. Genome Biol 4 (2):P1. Ogata H, Audic S, Abergel C, Fournier PE, Claverie JM (2002). Protein coding palindromes are a unique but recurrent feature in Rickettsia. Genome Res 12: 808-16. Quentin Y, Chabalier J, Fichant G. (2002). Strategies for the identification, the assembly and the classification of integrated biological systems in completely sequenced genomes. Comput Chem 26(5): 447-57. Renesto P, Crapoulet N, Ogata H, La Scola B, Vestris G, Claverie JM, Raoult D (2003). Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 362: 447-9. Solano PJ, Mugat B, Martin D, Girard F, Huibant JM, Ferraz C, Jacq B, Demaille J, Maschat F. (2003). Genome-wide identification of in vivo Drosophila Engrailed-binding DNA fragments and related target genes. Development 130: 1243-54. Thieffry D, Sánchez L (2002). Alternative epigenetic states understood in terms of specific regulatory structures. An NY Acad Sci 981: 135-53. Thieffry D, Sánchez L (2003). Dynamical modelling of pattern formation during embryonic development. Curr Opin in Genet Dev 13: 326-30.

  29. Valorisation Ipsogen (founded in 1999)Conception of DNA arraysELOGE: Sofware environment for functional genomics(DNA chip data processing, identification of transcriptional signatures for diagnosis) IGS laboratory (J-M. Claverie)Aventis-CNRS joint venture in structural genomics Phylogenics (founded in 2002)Software platform for the annotation of genomes based on genomic comparisons and phylogeny

  30. Bioinformatics at the Marseille-Nice Genopole Conclusions The genopole has played a crucial role in the development of interdisciplinary research Despite limited specific and direct financing, consequent results in terms of software produces, international publications and (inter)national funding Prospects Expansion of the teaching plate-form to facilitate the use of computational biology tools by all interested research teams (various kinds of access, professional courses) and gain more global visibility

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