1. Lecture 3: Pathway Generation Tool I: CellDesigner: A modeling tool of biochemical networks Y.Z. Chen Department of Pharmacy National University of Singapore Tel: 65-6616-6877; Email: phacyz@nus.edu.sg ; Web: http://bidd.nus.edu.sg phacyz@nus.edu.sghttp://bidd.nus.edu.sgphacyz@nus.edu.sghttp://bidd.nus.edu.sgContent CellDesigner overviewCellDesigner overview Introduction of systems biology platforms and software used by CelldesignerIntroduction of systems biology platforms and software used by Celldesigner CellDesigner versions and featuresCellDesigner versions and features

2. 2 What is Celldesigner? What is Celldesigner?

3. 3

4. What is CellDesigner? A structured diagram editor for drawing gene-regulatory and biochemical networks Networks are drawn based on the process diagram, with graphical notation system proposed by Kitano, and are stored using the Systems Biology Markup Language (SBML, a standard for representing models of biochemical and gene-regulatory networks).graphical notation system Systems Biology Markup Language (SBML Networks are able to link with simulation and other analysis packages through Systems Biology Workbench (SBW) Systems Biology Workbench (SBW)

5. What is CellDesigner? CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver (what is ODE?). SBML ODE Solver what is ODE By using CellDesigner, you can browse and modify existing SBML models with references to existing databases, simulate and view the dynamics through an intuitive graphical interface.

6. Systems Biology Graphical Notation A visual notation for network diagrams To help standardize a graphical notation for computational models in systems biology A natural complement to SBML Link to SBGN webpage online document

7. 7 Systems Biology Graphical Notation Systems Biology Graphical Notation

8. Systems Biology Graphical Notation Link to SBGN webpage, online documentSBGN webpageonline document

9. Systems Biology Graphical Notation Step 1: Block diagram

10. Systems Biology Graphical Notation Step 2: Molecular Interaction Map

11. Systems Biology Graphical Notation Step 3: Edinburgh Notation

12. Systems Biology Graphical Notation Step 3: Edinburgh Notation

13. Systems Biology Graphical Notation

15. Please read this online manual as part of your homeworkonline manual

16. Systems Biology Graphical Notation

19. 19 Systems Biology Markup Language Systems Biology Markup Language

20. Systems Biology Markup Language A computer-readable format for representing models of biochemical reaction networks. Applicable to metabolic networks, cell-signaling pathways, regulatory networks, and many others. Supported by over 120 software systems (as of Jan 2008)

21. 21 Systems Biology Markup Language Systems Biology Markup Language

22. 22 Systems Biology Markup Language Systems Biology Markup Language

23. 23 Systems Biology Markup Language Systems Biology Markup Language

24. Systems Biology Markup Language Please read SBML manualSBML

25. Systems Biology Markup Language SName

26. Systems Biology Markup Language Rules

27. Systems Biology Markup Language Definition of rule and derived types

28. Systems Biology Markup Language Mathematical functions

29. Systems Biology Markup Language Rate law functions

30. Systems Biology Markup Language Rate law functions

31. Systems Biology Markup Language Rate law functions

32. Systems Biology Markup Language Rate law functions

33. Systems Biology Markup Language Symbols

34. Systems Biology Markup Language Symbols

35. Systems Biology Markup Language Symbols

36. Systems Biology Markup Language Symbols

37. The SBML ODE Solver Library The SBML ODE Solver Library A programming library and a command-line application for symbolic and numerical analysis of a system of ordinary differential equations (ODEs) derived from a chemical reaction network encoded in the Systems Biology Markup Language (SBML).programming library Systems Biology Markup Language (SBML Written in ANSI/ISO C and distributed under the terms of the GNU Lesser General Public License (LGPL)ANSI/ISO C GNU Lesser General Public License (LGPL) The package employs libSBML's AST (Abstract Syntax Tree) for formula representation to construct ODE systems, their Jacobian matrix and other derivativeslibSBML SUNDIALS' version of CVODE is incorporated for numerical integration and sensitivity analysis of stiff and non-stiff ODE systems.SUNDIALSCVODE

38. The SBML ODE Solver Library The SBML ODE Solver Library The native API provides fine-grained interfaces to all internal data structures, symbolic operations and numerical routines, enabling the construction of powerful and efficient analytic applications, hybrid solvers or multi-scale models with interfaces to non SBML data sources.native API Optional modules based on Graphviz and XMGrace allow a quick inspection of a model's structure and dynamics.GraphvizXMGrace All functionalities are accessible directly via a command- line application and several example programs. Applications using SOSlib: CellDesigner, SBMLodeSolveR, SOSlib integration server, PyLESSCellDesigner SBMLodeSolveRSOSlib integration serverPyLESS

39. Celldesigner Versions Celldesigner Versions

41. Celldesigner Features Celldesigner Features