BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer” ICSB Web-services - 28 August 2008

BiNoM purpose in two words ICSB Web-services - 28 August 2008 BioPAX CellDesigner Cytoscape …very user friendly, but the possibilities to analyze and manipulate the diagram are limited …very interactive, but the support of existing Systems biology standards is very limited …very useful, but no easy tools for creating and editing BiNoM: 1)Easy manipulations of SB standards 2)Cytoscape environment 3)Java library decoupled from GUI 4)Tools for network analysis

ICSB Web-services - 28 August 2008 BiNoM platform (Zinovyev et al., Bioinformatics, 2008) Some Functions of the version 1.0: Import of BioPAX, SBML, CellDesigner and simple influence network formats Export to BioPAX, SBML and CellDesigner formats after user manipulations Network clipboard Conversion between standards (CellDesigner->BioPAX, BioPAX->SBML) Full support of BioPAX information (reaction network, interaction network, pathway structure, references) Editing BioPAX content Structural analysis of the networks (extracting strongly connected components, clustering relevant cycles, structural pathway analysis, modular network representation, path analysis) Biological network databases query system BiNoM I/O BiNoM Utilities BiNoM Structure analysis BiNoM BioPAX Query BiNoM BioPAX Utilities

Typical scenarios ICSB Web-services - 28 August )Import CellDesigner diagram, manipulate, convert to BioPAX 2)Import CellDesigner diagram, put colors and save it back 3)Import CellDesigner diagram, analyze, decompose into modules, create a modular view of the diagram 4)Import BioPAX file, extract a part, export to SBML, create a model 5)Import BioPAX file, edit, save it back 6)Index huge BioPAX file (whole Reactome), make a query, save result as small BioPAX file 7)Create a new BioPAX file from simple text file etc.

BiNoM notion of network index ICSB Web-services - 28 August 2008 BiNoM index (attributed graph) BiNoM interfaces (subgraphs) BiNoM query mechanism (extract subgraph) Standard SB file

Limited SBGN notation support

Naming convension

1: Working with CellDesigner files (importing/converting) ICSB Web-services - 28 August 2008 BioPAX

1: Working with CellDesigner files (analysis) Calzone et al. Comprehensive modular map of RB/E2F pathway. Molecular Systems Biology, 2008 Graph pruning, extracting strongly connected components, decomposition into cycles, finding shortest, subpotimal, all paths, clustering subgraphs, etc...

1: Working with CellDesigner files (coloring)

1: Working with CellDesigner files (generating web- sites)

2: Working with BioPAX files ICSB Web-services - 28 August 2008

Reaction network representation reactions proteins (species) complexes (species)

ICSB Web-services - 28 August 2008 Pathway structure representation pathway Pathway step

ICSB Web-services - 28 August 2008 ‘Protein interactions’ representation proteins (entities) complexes (entities)

Basic BioPAX editor

Pathway Database -> BioPAX -> BiNoM query Cancer Cell Map Reactome BioBase INOH BioCyc Nature/NCI Pathway Interaction Pathway Commons BiNoM Big BioPAX file

To work with big BioPAX file, BiNoM generates index (connection graph) Reactome.owl file Reactome Index.xgmml file BiNoM Query Network

Example of query

Examples of query … Give all interactions in which IGF1 participates … Give all interactions connecting given proteins

… Give the shortest path connecting given proteins

Export to BioPAX Export to SBML … Give the shortest and suboptimal paths connecting given proteins

Create BioPAX file from a simple text file (Facts sheet) 1) Defining families 2) Consistency check

Create BioPAX file from a simple text file (Facts sheet) Export to BioPAX Export to SBML

Nearest future development ICSB Web-services - 28 August )BioPAX 3.0 support 2)CellDesigner format 4.0 support 3)Creating BiNoM plug-in for CellDesigner 4.0 4)New structural analysis algorithms

Install and Start Cytoscape+BiNoM Note: BiNoM is not yet compatible with the latest version of Cytoscape These technical issues will be resolved very soon Detailed manual + Tutorial are available! Reference: Zinovyev et al, Bioinformatics 2008

Acknowledgements ICSB Web-services - 28 August 2008 Eric Viara Laurence Calzone Gautier Stoll Emmanuel Barillot EU FP6 project ESBIC-D (LSHG-CT ) High Council for Scientific and Technological Cooperation between France and Israel