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BI ological N etwO rk M anager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer” http://bioinfo.curie.fr/sysbio ICSB Web-services - 28 August 2008

BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

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Page 1: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

BIological NetwOrk Manager Cytoscape plugin

Andrei ZinovyevInstitut Curie/INSERM/Ecole de Mines, UMR 900

“Computational Systems Biology of Cancer”http://bioinfo.curie.fr/sysbio

ICSB Web-services - 28 August 2008

Page 2: 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

Page 3: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

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 existingSystems biology standards is very limited

…very useful, but no easy tools for creating and editing

BiNoM:1)Easy manipulations of SB standards2)Cytoscape environment3)Java library decoupled from GUI4)Tools for network analysis

Page 4: 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 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

Page 5: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Typical scenarios

ICSB Web-services - 28 August 2008

1) 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.

Page 6: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

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

Page 7: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Limited SBGN notation support

Page 8: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Naming convension

Page 9: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

1: Working with CellDesigner files (importing/converting)

ICSB Web-services - 28 August 2008

BioPAXBioPAX

Page 10: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

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...

Page 11: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

1: Working with CellDesigner files (coloring)

Page 12: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

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

http://bioinfo.curie.fr/projects/rbpathway

Page 13: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

2: Working with BioPAX files

ICSB Web-services - 28 August 2008

Page 14: 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

Reaction network representation

reactions

proteins (species)

complexes (species)

Page 15: 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

Pathway structure representation

pathway

Pathway step

Page 16: 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

‘Protein interactions’ representationproteins (entities)

complexes (entities)

Page 17: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Basic BioPAX editor

Page 18: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Pathway Database -> BioPAX -> BiNoM query

Cancer Cell Map

Reactome

BioBase

INOH

BioCyc

Nature/NCI Pathway Interaction

Pathway Commons

BiNoM

Big BioPAX

file

Page 19: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

To work with big BioPAX file, BiNoM generates index (connection graph)

Reactome.owl file

ReactomeIndex

.xgmml fileBiNoM BiNoM

Query

Network

Page 20: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Example of query

Page 21: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Examples of query

… Give all interactions in which IGF1 participates

… Give all interactions connecting given proteins

Page 22: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

… Give the shortest path connecting given proteins

Page 23: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Export to BioPAXExport to SBML

… Give the shortest and suboptimal paths connecting given proteins

Page 24: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Create BioPAX file from a simple text file (Facts sheet)

1) Defining families 2) Consistency check

Page 25: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Create BioPAX file from a simple text file (Facts sheet)

Export to BioPAXExport to SBML

Page 26: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Nearest future development

ICSB Web-services - 28 August 2008

1) BioPAX 3.0 support

2) CellDesigner format 4.0 support

3) Creating BiNoM plug-in for CellDesigner 4.0

4) New structural analysis algorithms

Page 27: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Install and Start Cytoscape+BiNoM

Note: BiNoM is not yet compatible with the latest version ofCytoscape 2.6.0. These technical issues will be resolved very soon

Detailed manual + Tutorial are available!

Reference: Zinovyev et al, Bioinformatics 2008

Page 28: BIological NetwOrk Manager Cytoscape plugin Andrei Zinovyev Institut Curie/INSERM/Ecole de Mines, UMR 900 “Computational Systems Biology of Cancer”

Acknowledgements

ICSB Web-services - 28 August 2008

Eric Viara

Laurence Calzone

Gautier Stoll

Emmanuel Barillot

EU FP6 project ESBIC-D (LSHG-CT-2005-518192)

High Council for Scientific and Technological Cooperation between France and Israel