1. CellDesigner Tutorial Laurence Calzone, Andrei Zinovyev UMR U900 INSERM/Institut Curie/Ecole des Mines de Paris Wednesday, April 30th

2. Outline CellDesigner Tutorial - Practice Example

3. Variety of models: example of NFkB A model can be represented in many different ways:

4. Many representations for the same model. => Each modeler uses its own representation => Need to read the paper to understand the model => Before being able to use or translate models into mathematics, need to understand the modeler’s symbols => Need for a standard format to be able to - use models - exchange models - compare models - compose models - etc.

5. Standard formats SBML (Systems Biology Markup Language) format for representing models of biochemical reaction networks Over 100 software packages support SBML BioPAX (Biological PAthway eXchange) format for storing biological pathway data; ontology for describing biochemical processes and their hierarchies SBGN (Systems Biology Graphical Notation) format for representing graphically biological interactions e.g. protein-protein interaction, gene regulatory networks, etc.

6. CellDesigner: a short overview

7. What is CellDesigner? CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks that uses standard formats.

8. CellDesigner content Full SBML support Graphical notation (SBGN) Possibility for mathematical simulations Database connection Export to PDF, PNG, … Freely available Supported Environment –Windows (2000 or later) –Mac OS X –Linux

9. What is CellDesigner good for? CellDesigner: Offers an « easy-to-use » graphical representation of a network Facilitates exchange of models developed by different groups, using a standard language (SBML: Systems Biology Markup Language) Allows to annotate the reactions, proteins, genes, etc. Proposes links to other databases (PubMed, IHOP, BioModels, KEGG, etc.) Organizes a lot of information in a unique diagram Allows an exchange with other modeling tools

10. Install and Start CellDesigner Download CellDesigner version 4.0 β from http://celldesigner.orghttp://celldesigner.org Download: Setup: Launch:

11. Start CellDesigner

12. CellDesigner screen

13. General view TREE AREA displays all the list of the components in a tree structure. DRAW AREA is the area where the model is built from the tool bar items. LIST AREA displays and edits the list of the components of the model (species, proteins, genes, RNAs, etc.) NOTES AREA displays and edits the notes of each component (reactions, protein, complex, etc.) TreeDrawing List Notes Layer

14. The menu Compartment menu Chemical species menu Reaction menu Boolean logic menu Visualization menu

16. The chemical species

17. The reactions

18. The compartments Compartments can be: - Cytoplasm - Nucleus - Nucleolus - etc.

19. Boolean gates Introduce boolean logic information into the diagram

20. Start with a simple network - Open a new document: [File] => [New] - Name your network (MichaelisMenten) - Choose the dimension of the graph (by default: 600 by 400 but can be changed later)

21. Add proteins - Choose to add a protein from the Species menu - A pop-up window opens: name your protein - Repeat the process as many times as needed

22. Add complexes - Choose to add a complex from the Species menu - Name it - Insert the proteins that compose the complexes (you must copy/paste the proteins from the diagram itself and move them inside the complex)

23. Connect species - Choose the heretodimer association to connect the proteins E, S and the complex ES (there are many reaction types to link two species) - An alternative: a macro, allows to do all these steps in just one step

24. Examples of macros

25. Small network Note: There is a possibility to include dynamics into the diagram by defining the parameters re1, re4, re3… We will not describe this process today… This biochemical reaction is translated into this diagram

26. Or more simply… You choose the level of details… This reaction is translated into this diagram

27. Some functions Drawing tips: - Choose from the [Edit] menu, Grid Snap, to help you draw your network. - You can also make the grid visible Grid Snap On or OFF indicated here

28. Search Database by Notes: PubMed: PMID: 123456 Entrez Gene: GeneID: 4015 Database Connection

29. Import model from BioModels.net Database Connection

30. Practice

31. Inventory of features Open a new model Create a reaction Add anchor point Add catalytic reaction Set active state Change color Include compartment Add residue to protein Change position of residue Create complex Include genes and RNAs Connect to databases Choose layout

32. Demo

33. First mathematical model of NFkB