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Introduction. CSB.DB - A Comprehensive System-Biology Database - Hosted at Max Planck Institute of Molecular Plant Physiology Bjoern Usadel Dirk Steinhauser CSB.DB – Development Core Team Research groups: Plant Cell Walls (M. Pauly) & Root Metabolism (J.Kopka)
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Introduction CSB.DB - A Comprehensive System-Biology Database - Hosted at Max Planck Institute of Molecular Plant Physiology Bjoern Usadel Dirk Steinhauser CSB.DB – Development Core Team Research groups: Plant Cell Walls (M. Pauly) & Root Metabolism (J.Kopka) URL: http://csbdb.mpimp-golm.mpg.de/ Max Planck Institute of Molecular Plant Physiology Steinhauser, D., Usadel, B., Luedemann, A., Thimm, O. & Kopka, J. (2004a) Bioinformatics, accepted
CSB Project Goals: • new easily accessible knowledge about the relationship / hierarchy of cellular components • understanding life’s complexity pyramid • formulation of hypotheses about the respective functional involvement of compounds / their (inter-) relationships Life`s Complexity Pyramide The multidisciplinary crosstalk Bioinformatics Bioengineering & Bionics Biostatistics CSB.DB Ecology Biophysics Biology Evolution Molecular Biology & Physiology Biochemistry Max Planck Institute of Molecular Plant Physiology Oltvai, Z.N. & Barabási, A.-L. Life`s Complexity Pyramide. Sciene 298, 763-764 (2002)
Co-Response Analyses • Association among entities: Genes, Proteins, Enzyme activities, Metabolites co-regulated entities • Functional prediction of sets of non-homologous genes • Identification of genes which embody a specific functional category: marker genes • Evolution & gene (co-response) • Co-Response measure: Correlation, Distances, Mutual Information Similarity measures Pearson KendallSpearman ... Distance measures Euclidean Manhattan ... Max Planck Institute of Molecular Plant Physiology
CoR.DBs CSB.DB: Profile Processing EXPT Genes - publicly available - well measurements - manual assignments EXPT - NA omit (5%) - subsets - conditional - global Genes Genes Software-Development@CSB.DB - non- / semi- / parametric - distance / similarity - incl. statistics (pval, power,CI) - large data sets cCoRv1.0: Max Planck Institute of Molecular Plant Physiology
APACHE CSB.DB: System Architecture • public web interface large scale stat. analyses • became operational in March 2004 Database SAP DB R statistical package R PM Client Site CGI Call CoRDB Server Perl CGI Txt WWW Client Text Files HTML cCoR PM Java Applet Tmp Programs Interactive Applet Tmp Folder: gif‘s Web Server CGI-Script Modules CoRDB Server SuSE Linux Server Site Max Planck Institute of Molecular Plant Physiology
CAWPs CSB.DB PSDB MSRI SynCoR EcoCoR LesCoR AthCoR SceCoR CoRDBs MADBs CSB.DB Structure: current & future Higher order organisation Organism specificity Universality Genome CSB.DB Associated Web Pages Information Storage genes RNA Processing Proteins Co-Response Databases Analytic Execution metabolites Metabolic & Analytical Databases Metabolites Max Planck Institute of Molecular Plant Physiology
CSB.DB CoR.DBs Functions Query Types - Single (Gene) Query - Multiple (Gene) Query - Intersection (Gene) Query Query Group - Easy - Advanced Info / Help Default Settings Max Planck Institute of Molecular Plant Physiology
CSB.DB: Co-Response Query MapMan Visualisation: (Thimm et al., 2004) single / intersection gene query Functional Category Summary Tables (HTML) multiple gene query CoRNetApplet: Max Planck Institute of Molecular Plant Physiology Thimm et al. (2004) Plant J., 37, 914-939
CSB.DB Validation / Graphs CSB.DB Max Planck Institute of Molecular Plant Physiology
CSB.DB Proof of Concept E. coli Operon Prediction: Distribution of robust correlation among Operon genes & Non-operon genes Scheme: Hypotheses driven approach (HDA) • Results: • Unbiased cluster approach failed • Integration of additional information, i.e. chromosomal distance, increase precision of annotation Max Planck Institute of Molecular Plant Physiology Steinhauser, D., Junker, B.H., Luedemann, A., Selbig, J. & Kopka, J. (2004b) Bioinformatics, DOI: 10.1093/bioinformatics/bth182.
Outlook MapMan Visualisation: (Thimm et al., 2004) Context dependent Metabolic pathways PaVESy Visualisation: (Luedemann et al., 2004) Max Planck Institute of Molecular Plant Physiology Luedemann et al. (2004) Bioinformatics Advance Access published on April 22 Thimm et al. (2004) Plant J., 37, 914-939
Acknowledgements Contributors of CSB.DB Alexander Luedemann: CoRNetApplet Leonard Krall & Dirk Buessis: Improvements & Discussions Joachim Kopka: MSRI@CSB.DB Claudia Birkemeyer: Analytics@CSB.DB Oliver Thimm & Yves Gibon: MapMan Charles Guy & Co-Workers: Unpublished Experiments J. Selbig: Escherichia coli & Discussions Support of CSB.DB Joachim Kopka, Thomas Altmann, Lothar Willmitzer, Mark Stitt Biological Projects & Cooperation S. Kempa, C. Rautengarten & T. Altmann, J. Lisso & C. Müssig, W.R. Scheible, M. Udvardi, A. Niehl, F. Carrari, V. Nikiforova Server & Admin: E. Simmat & P. Krueger: Server administration & Discussions Max Planck Institute of Molecular Plant Physiology