PowerPoint Presentation

We present BiNoM [1,2], a Cytoscape plugin, developed to facilitate the manipulation of biological networks represented in standard systems biology formats (SBML, CellDesigner, BioPAX) and to carry out studies on the network structure. BiNoM provides the user with a complete interface for the analysis of biological networks in the Cytoscape environment. The BiNoM project is open-source (http://binom.curie.fr and http://apps.cytoscape.org/apps/binom) and can be used to study biological processes such as the cell cycle in bladder carcinoma cells or epithelial-to-mesenchymal transition in mouse models of colon cancer. , a Cytoscape plugin for accessing and analyzing pathways using standard systems biology formatsEric Bonnet1,2,3, Laurence Calzone1,2,3 , Daniel Rovera1,2,3, Gautier Stoll 1,2,3, Paola Vera-Licona1,2,3 , Emmanuel Barillot1,2,3 and Andrei Zinovyev1,2,3 [1] Institut Curie, 26 rue d'Ulm, Paris, F-75248 France; [2] INSERM, U900, Paris, F-75248 France; [3] Mines ParisTech, Fontainebleau, F-77300 France.Import and export of BioPAX Level 3, SBML Level 2 and CellDesigner (version 3.x and 4.x) files. Conversion between different formats (e.g. CellDesigner to BioPAX, BioPAX to SBML). Note that the latest level of BioPAX, level 3 (released in 2010), is now supported by BiNoM.

[ BiNoM I/O ][ Structural analysis ]

An example of a cycle decomposition result: the life cycle of the isolated protein, CDC25.An example of a material decomposition result: the phosphorylated form of CDC25 is forming a cycle with the complex CDC13/CDC2.

Modularization: A set of sub-networks, obtained for example using cycle or material decomposition, can be grouped to generate a novel modular view of the network.Modular view created from six sub-networks, obtained using the get material component function. The original network is the yeast M phase cell cycle model. The green nodes indicate sub-networks that have been clustered together.BiNoM offers several tools and functions for the structural analysis of networks.Material or Cycle decomposition: The decomposition of a network into directed cycles is often giving information about the life cycle of a protein. The material components decomposition is using name semantics to isolate sub-networks in which each protein is involved.

[1] Zinovyev A., Viara E., Calzone L., Barillot E. BiNoM: a Cytoscape plugin for manipulating and analyzing biological networks. 2008. Bioinformatics 24(6):876-877.[2] Bonnet E., Calzone L., Rovera D., Stoll G., Barillot E. and Zinovyev A. BiNoM 2.0, a Cytoscape plugin for accessing and analyzing pathways using standard systems biology formats. BMC Systems Biology (submitted).[3] Calzone L., Gelay A., Zinovyev A., Radvanyi F., Barillot E. A comprehensive modular map of molecular interactions in RB/E2F pathway. 2008.Molecular Systems Biology4:174.Work supported by the EU FP7 ASSET project and by a grant from the Projet Incitatif et Collaboratif Computational Systems Biology Approach for Cancer from Institut Curie. The team Computational Systems Biology of Cancer is an Equipe labellise par la Ligue Nationale Contre le Cancer.[ Optimal combination of intervention sets ]Influence graph G.Input nodes I1, I2.Output (target) nodes O1, O2.I1 -> B -> C -> O1I1 -> E -> C -> O1I2 -> E -> C -> O1Intervention sets: {C}, {E, B}, {I1, I2}Minimal: {C} Ok, minimal.{E, C} Not good, not minimal.

Alpha: activity of the pathSigma: sign of the pathLambda: length of the path[ Pathway Influence Quantification ]The PIQuant (Pathway Influence Quantification) algorithm is a scoring function that integrates experimental data and network architecture in a quantitative score.

Heatmap visualisation of PIQuant scores. The scores were calculated for a cell cycle network (G1/S phase) composed of 46 nodes and 130 edges. We selected three nodes as representative phenotypes of the cell cycle phases G, S and M.Algorithms implemented in OCSANA:Exact solution: Berges algorithm.Approximation solution: suitable for large networks.Application of OCSANA: candidate drug target discovery.

[ BiNoM case study ]We used BiNoM to import a large molecular map of the RB/E2F cell cycle [3]. This map is composed of 78 proteins, 530 reactions, 176 genes and 215 chemical species. The map was modularized in 15 modules using BiNoM functions and expert knowledge. Each node represent a set of reactions. This abstract representation can be used for modeling, or for mapping omics data.

Modular RB/E2F maps, with bladder cancer transcriptomic data from invasive and non-invasive stages mapped on the modules, showing differential activations and inhibitions.

Full RB/E2F maps, stained with the same expression data as above for each gene, showing different patterns for the invasive and non-invasive tumor stages.Invasive cancers

Non-invasive cancers