Analysis of biomolecular networks Jacques van Helden Jacques.van-Helden@univ-amu.fr Aix-Marseille Université (AMU) Lab. Technological Advances for Genomics and Clinics (TAGC, INSERM Unit U1090) http://jacques.van-helden.perso.luminy.univ-amu.fr/ FORMER ADDRESS (1999-2011) Université Libre de Bruxelles, Belgique Bioinformatique des Génomes et des Réseaux (BiGRe lab) http://www.bigre.ulb.ac.be/ B!GRe Bioinformatique des Génomes et Réseaux Bioinformatique des Génomes et des Réseaux (BiGRe) Université Libre de Bruxelles http://www.bigre.ulb.ac.be/ ! ! Conception, implementation, evaluation and application of bioinformatics methods for the analysis of genomes and biomolecular networks. Regulatory sequences Motif analysis algorithms (Olivier Sand , Matthieu Defrance , Maud Vidick, Alejandra Medina-Rivera) " Evolution of cis-acting elements in Bacteria (Rekin’s Janky, Alejandra Medina-Rivera) " Regulation of development in Drosophila (Jean Valéry Turatsinze, Elodie Darbo) " Hox regulation in Vertebrates (Morgane Thomas-Chollier) " Work flows on transcriptional regulation (Olivier Sand, Eric Vervisch) Biomolecular networks " Network analysis tools (Sylvain Brohée) " Inference of metabolic pathways (Karoline Faust, Didier Croes ) " Host-virus interaction networks (Nicolas Simonis, Leon Juvénal Hagingambo) " Analysis of regulatory networks (Sylvain Brohée, Rekin’s Janky) Mobile genetic elements in prokaryotes (Raphaël Leplae, Gipsi Lima, Ariane Toussaint) Modelling of dynamical systems (Didier Gonze) e-Learning for bioinformatics (Guy Bottu) " Sylvain Brohée Postdoc Nicolas Simonis Postdoc Didier Croes Postddoc Didier Gonze Myriam Loubriat Premier assistant Secretary ! Ariane Toussaint Jacques van Helden Professor Emeritus Professor Leon Juvenal HajingaboE Maud Vidick PhD Student (co-direction) PhD Student Elodie Darbo PhD Student co-direction Marseille ! ! Alejandra Medina PhD Student co-direction Mexico Raphaël Leplae Ex-Postdoc Morgane Thomas-Chollier Matthieu Defrance Ex-Postdoc Ex-PhD student+postdoc Gipsi Lima Ex-PhD + Postdoc Olivier Sand Ex-Postdoc Jean Valéry Turatsinze ! Ex-PhD student Karoline Faust Ex-PhD student Rekin’s Janky Ex-PhD student Eric Vervisch Ex-Research fellow Guy Bottu Ex-Postddoc 2 B!GRe Bioinformatique des Génomes et Réseaux ! Regulatory Sequence Analysis Tools (RSAT, http://rsat.ulb.ac.be/rsat/) " ! Bioinformatique des Génomes et des Réseaux (BiGRe) Université Libre de Bruxelles http://www.bigre.ulb.ac.be/ Detection of cis-regulatory elements in nucleic sequences (pattern discovery, pattern matching, phylogenetic footprints, regulatory networks, ChIP-seq analysis) Network Analysis Tools (NeAT, http://rsat.ulb.ac.be/neat/) " " A toolbox for analyzing networks, pathways and clusters. Protein-protein interactions, metabolic pathways, genetic mobility, regulatory networks, … 3 Network Analysis Tools (Neat, http://rsat.ulb.ac.be/neat/) ! ! ! NeAT: a toolbox for analyzing networks, clusters and pathways. A variety of approaches " Network comparisons. " Network-based clustering. " Metabolic path finding. " Sub-network extraction. Three access modes " User-friendly Web site. " Stand-alone version. " Web services. Sylvain Brohée Ex-PhD student Karoline Faust Ex-PhD student Gipsi Lima Postdoc Brohee et al. (2008). NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways. Nucleic Acids Res 36, W444-51. Brohee et al. (2008). Network Analysis Tools: from biological networks to clusters and pathways. Nature Protocols 3, 1616-29. 4 Scope of the course ! ! ! Scope: theory + practice Target audience: students from computer sciences + life sciences. Theory " " " ! Introduction to network biology Network types • Protein interactions (interactome) • Genetic interactions • Metabolism • Regulatory • Integrative Analytic approaches • Topological organization of biological (and other) networks • Path finding and subgraph extraction • Network comparisons • Network-based clustering (module extraction) • Recurrent network motifs • Relationship between network structure and dynamical behaviour Practicals " " Browsing, downloading and visualizing networks Applications of all the analytic approaches above to selected study cases Links and references ! Network Analysis Tools " ! http://rsat.ulb.ac.be/neat/ Main publications related to the tools 1. Faust, K., Dupont, P., Callut, J. and van Helden, J. (2010). Pathway discovery in metabolic networks by subgraph extraction. Bioinformatics 26:1211-8. 2. Lima-Mendez, G. and van Helden, J. (2009). The powerful law of the power law and other myths in network biology. Mol. BioSyst., 2009, 5, 1482 - 1493, DOI: 10.1039/b908681a. 3. Faust, K., Croes, D. and van Helden, J. (2009). In response to "Can sugars be produced from fatty acids? A test case for pathway analysis tools". Bioinformatics 2009 Sept 23. 4. Faust K., Croes, D., van Helden J. (2009). Metabolic Pathfinding Using RPAIR Annotation. Journal of Molecular Biology 388, 390-414. 5. Brohée S., Faust K., Lima-Mendez G., Vanderstocken G., van Helden J. (2008). Network Analysis Tools: from biological networks to clusters and pathways. Nature protocols 3 (10), 1616-29. 6. Brohée, S., Faust, K., Lima-Mendez, G., Sand, O., Janky, R., Vanderstocken, G., Deville, Y. & van Helden, J. (2008). NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways. Nucleic Acids Research 36, W444-451. 7. Brohée, S. & van Helden, J. (2006). Evaluation of clustering algorithms for protein-protein interaction networks. BMC Bioinformatics 7, 488. Pubmed 17087821 8. Croes, D., F. Couche, S.J. Wodak, J. van Helden (2006). Inferring Meaningful Pathways in Weighted Metabolic Networks. J. Mol. Biol. 356:222-36. Pubmed 16337962 9. Croes, D., F. Couche, S.J. Wodak, and J. van Helden. 2005. Metabolic PathFinding: inferring relevant pathways in biochemical networks. Nucleic Acids Res 33: W326-330. 10. van Helden, J., Wernisch, L., Gilbert, D. & Wodak, S. J. (2002). Graph-based analysis of metabolic networks. In Ernst Schering Res Found Workshop (al., M. H.-W. e., ed.), pp. 245-74. Springer-Verlag. 11. van Helden, J., Gilbert, D., Wernisch, L., Schroeder, M. & Wodak, S. (2001). Applications of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data. Computational Biology : First International Conference on Biology, Informatics, and Mathematics, JOBIM 2000. LNCS volume 2066, Montpellier. Acknowledgements Bioinformatique des Génomes et des Réseaux (BiGRe) http://www.bigre.ulb.ac.be/ Network Analysis Tools (NeAT, http://rsat.ulb.ac.be/neat/) # Sylvain Brohée # Karoline Faust # Gipsi Lima-Mendez Programs from external developers ! Stijn van Dongen (Sanger, UK) for MCL ! Igor Jurisica (USA) for RNSC Metabolic path finding (NeAT, http://rsat.ulb.ac.be/neat/) # Karoline Faust # Pierre Dupont (UCL, Belgium) for kWalks # Shoshana Wodak # Didier Croes # Fabian Couche # The aMAZE team Interactome et cancer # # Nicolas Simonis Léon Juvénal Hagingambo Former collaborators of the aMAZE project # Yves Deville (UCL) # Grégoire Dooms (UCL) # Pierre Schaus (UCL) # Stéphane Zampelli (UCL) # Lorenz Wernisch (Birbick college, UK) # David Gilbert (London City – UK) # Georges Cohen (Institut Pasteur - France) Former aMAZE team # Shoshana Wodak # Hassan Anerhour # Erick Antezana # Jean Richelle # Xavier Santaloria # Jesintha Maniraja # Christian Lemer # Olivier Hubaut # Fabian Couche # Frederic Fays # Simon De Keyzer Funding sources # # # # # EU VIth framework (BioSapiens project) Belgian FNRS - Action de Recherche Concertée Belgian FRIA – PhD grants Région Bruxelloise de Belgique (aMAZE project) Région Wallonne de Belgique (BioMaze + TransMaze projects) Proverbios y cantares - XXIX Caminante, son tus huellas el camino y nada más; Caminante, no hay camino, se hace camino al andar. Al andar se hace el camino, y al volver la vista atrás se ve la senda que nunca se ha de volver a pisar. Caminante no hay camino sino estelas en la mar. Antonio Machado Marcheur, ce sont tes traces le chemin, et rien de plus ; Marcheur, il n'y a pas de chemin, Le chemin se construit en marchant. En marchant se construit le chemin, Et en regardant en arrière On voit la sente que jamais On ne foulera à nouveau. Marcheur, il n'y a pas de chemin, Seulement des sillages sur la mer. Traduction de José Parets-LLorca Wanderer, it is your tracks which are the road, and nothing else. Wanderer, there is no road, walking makes the road. By walking, the road is made, and when glancing back you contemplate the trail which you will trample no more. Wanderer, there is no road, only the wakes on the sea. Traduction Roger LAPOINTE