Atlas of Cancer Signaling Networks (ACSN) and NaviCell are user- friendly web- based environments for integra)ve systems biology of cancer

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1 Atlas of Cancer Signaling Networks (ACSN) and NaviCell are user- friendly web- based environments for integra)ve systems biology of cancer Inna Kuperstein Computa)onal Systems Biology of Cancer U900 Ins)tut Curie/INSERM/Ecole des Mines ParisTech, Paris, France

2 What will arract scien)fic community to par)cipate in model crea)on, sharing and update? Addressing the following ques)ons: Google map 1. How to ensure efficient model sharing (easy access repository)? 2. How to allow model explora)on (efficient naviga)on tool)? 3. How to organize model cura)on by scien)fic community and model update (forum for model commen)ng and maintenance)?

3 A web tool for naviga)on, cura)on and maintenance of large models NaviCell = map (Google Maps engine) + Blog (WordPress) Provides advanced naviga)on features (seman)c zooming; supports hierarchical structure of maps) Google map Blog Google map Seman)c zoom NaviCell: a web tool for naviga)on, cura)on and maintenance of large molecular interac)on maps. Kuperstein I, Pook S, Cohen DPA, Calzone L, Barillot E and Zinovyev A (in revison) hrp://navicell.curie.fr navicell@curie.fr

4 A web repository for available CellDesigner models NaviCell is a web tool suitable for visualiza)on, naviga)on and exposure for community cura)on of models from any collec)ons or databases or for individual projects

5 Atlas of Cancer Signaling Networks Atlas of Cancer Signalling Networks (rationale) hrp://acsn.curie.fr

6 Atlas of Cancer Signaling Networks Atlas of Cancer Signalling Networks (structure) hrp://acsn.curie.fr

7 Atlas of Cancer Signalling Networks (features) Features: Cancer- related Manually curated Comprehensive Interconnected Browsable and zoomable Applicable for data integra)on

8 Map/Module Apoptosis map AKT_MTOR CASPASES HIF1 MITOCH_METABOLISM MOMP_REGULATION TNF_RESPONSE APOPTOSIS_GENES Cell cycle map APOPTOSIS_ENTRY APC CDC25 CYCLINA CYCLINB CYCLINC CYCLIND CYCLINE CYCLINH E2F1 E2F4 E2F6 INK4 P21CIP P27KIP RB WEE Cell survival map WNT_NON_CANONICAL WNT_CANONICAL HEDGEHOG PI3K_AKT_MTOR MAPK Chemical species Atlas of Cancer Signalling Networks (content) Proteins Reactions References Creation date Last update Comparison of connec)vity (ACSN vs. REACTOME) DNA repair map CHECKPOINTS G1_S_CHECKPOINT S_PHASE_CHECKPOINT G2_M_CHECKPOINT SPINDLE_CHECKPOINT CELL_CYCLE G1_CC_PHASE S_CC_PHASE G2_CC_PHASE M_CC_PHASE DNA_REPAIR_PATHWAYS BER NER MMR HR NHEJ MMEJ FANCONI TLS SSA DR N.a N.a N.a PubMed IDs distribu)on (ACSN vs. REACTOME) EMT and cell motility map EMT_REGULATORS ECM CELL_MATRIX_ADHESIONS CYTOSKELETON_POLARITY CELL_CELL_ADHESIONS TIGHT_JUNCTIONS ADHERENS_JUNCTIONS DESMOSOMES GAP_JUNCTIONS ACSN global map !! ACSN global map Chemical Proteins Reactions References Creation date species

9 Standards and tools for signaling networks construc)on Visual syntax Systems Biology Graphical Nota)on (SBGN) Biological molecules and interac)ons representa)on Tool: CellDesigner Diagram editor for signalling networks representa)on The Systems Biology Graphical Nota)on. Le Novère N, et. al Nat Biotechnol Aug;27(8): Biochemical modeling with Systems Biology Graphical Nota)on. Jansson A, Jirstrand M. Drug Discov Today May;15(9-10):

10 ACSN DEMO

11 Conclusions - NaviCell is a tool that combines several essen)al features for map naviga)on, cura)on, maintenance - NaviCell uses exis)ng open- source interfaces (Google Maps engine, WordPress) - NaviCell is a repository of available models created in CellDesigner Google map - NaviCell can be used as a tool for visualiza)on, naviga)on and commen)ng of any models in exis)ng databases or for individual projects - ACSN is a repository of models related to signalling implicated in cancer - ACSN is created using systems biology standards and the content of ACSN is available in several exchange formats - ACSN is a way of represen)ng biological informa)on in the form of territory where biological processes are represented as con)nents and countries on atlas, in analogy with geographical maps

12 Acknowledgements Computa)onal Systems Biology of Cancer Group Ins)tut Curie, Paris Laurence Calzone Simon Fourquet David Cohen Hie- Anh Nughen Bruno Tesson Guillem Rigaill Stuart Pook Erio Bonnet Eric Viara Paola Vera- Licona Andrei Zinovyev Emmanuel Barillot Laboratory of Cell Signalling Ins)tut Curie, Paris Celine Baldeyron Thierry Dubois Ins)tut Curie, Paris Marc- Henri Stern Tatyana Popova Manolis Papamichos Suylvie Robine Daniel Louvard Maia Chanrion Ins)tut Curie, Orsay Mounira Amor- Guéret Janet Hall Marie Dutreix Ins)tut Gustave Roussy, Villejuif Murat Saparbaev Pilippo Roselli Patricia Kannouche University of California, Davis Wolf- Dietrich Heyer Ins)tut de Recherches Servier Cancer Research & Drug Discovery, Croissy sur Seine Gordon Tucker Francisco Cruzalegui