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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/
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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)
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Regulation of development in Drosophila (Jean Valéry
Turatsinze, Elodie Darbo)
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Hox regulation in Vertebrates (Morgane Thomas-Chollier)
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Work flows on transcriptional regulation (Olivier Sand, Eric
Vervisch)
Biomolecular networks
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Network analysis tools (Sylvain Brohée)
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Inference of metabolic pathways (Karoline Faust, Didier
Croes )
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Host-virus interaction networks (Nicolas Simonis, Leon
Juvénal Hagingambo)
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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)
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Sylvain Brohée
Postdoc
Nicolas Simonis
Postdoc
Didier Croes
Postddoc
Didier Gonze
Myriam Loubriat
Premier assistant
Secretary
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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
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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
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Ex-PhD student
Karoline Faust
Ex-PhD student
Rekin’s Janky
Ex-PhD student
Eric Vervisch
Ex-Research fellow
Guy Bottu
Ex-Postddoc
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B!GRe
Bioinformatique des
Génomes et Réseaux
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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/)
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A toolbox for analyzing networks, pathways and clusters.
Protein-protein interactions, metabolic pathways, genetic mobility, regulatory networks,
…
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Network Analysis Tools (Neat, http://rsat.ulb.ac.be/neat/)
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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.
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Scope of the course
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Scope: theory + practice
Target audience: students from computer sciences + life sciences.
Theory
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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
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Browsing, downloading and visualizing networks
Applications of all the analytic approaches above to selected study cases
Links and references
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Network Analysis Tools
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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
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Stijn van Dongen (Sanger, UK) for MCL
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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
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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
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