1. XML Documentation of Biopathways and Their Simulations in Genomic Object Net Speaker : Hungwei chen

2. Biopathway Modeling & Simulation

3. A Software Toward Biopathway Modeling & Simulation

4. Genomic Object Net

5. What is Genomic Object Net Genomic Object Net is a software tools for Modeling and Simulation Biopathways Employing the notion of HFPN as its basic Architecture Using XML Documents for representation simulations and visualization for Biopathway

6. About Genomic Object Net Genomic Object Net Assembler Genomic Object Net Describing tool. Genomic Object Net Visualizer

7. Biopathway Describing Tool –helps to describe a biopathway according to the traditional description methods in biology –releasing users from the mathematical knowledge Genomic Object Net Assembler 1.Designs HFPN which represents and simulates a system of genomic objects. 2.Produces Biopathway Representation Source File as an XML document. 3.Produces Simulation Results Files (CSV format) each of which contains a time-series of the numerical values representing the behavior of places in HFPN.

8. In order for biosimulation tools to be accepted by users in (1)Remove issues which are irrelevant to biological importance, (2)Allow users to represent biopathways intuitively and understand/manage easily the details of representation and simulation mechanism From these criteria, software tools currently developed might not be enough satisfactory.

9. Metabolic Pathways Signaling Pathways Gene Regulatory Networks Pathway Types for Modeling

10. Metabolic Pathway

11. Apoptosis induced by Fas Cytoplasm cascade caspase Signal Fas ligand Fas receptor complex Signaling Pathway

12. Switching Mechanism of Lambda Phage

13. Petri net place transition arc inhibitory arc token

14. What is the Petri Net ?? A Petri Net is a collection of directed arcs connecting places and transitions. Arcs have capacity 1 by default. Places may hold tokens transitions have no capacity, and cannot store tokens.

15. Simple Example of Petri Net

16. How to enable token through transition A transition is enabled when the number of tokens in each of its input places is at least equal to the arc weight going from the place to the transition. An enabled transition may fire at any time. When fired, the tokens in the input places are moved to output place

17. Example of Petri Net Graph

18. When arcs have different weights

19. The inhibitor arc This transition cannot fire, because the token in P2 inhibits it.

20. Petri Net Topology

21. Example-the control of a vending machine

22. A coin is ready to drop

23. An accepted coin leads to dispensing

24. After inserting several coins

25. 2H2 + O2 -> 2H2O

26. Hybrid Petri Net Easy to describe biological facts and biological phenomenon on computers and Acceptable technical expression of the tool to biologists. Extension to Hybrid Dynamic Net © Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo

27. Elements Michaelis - Menten Equation Hybrid Dynamic Net © Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo

28. Hybrid functional Petri net Assign any function to each arc Transition T fires as long as m i > 0 for all 1 < i < p © Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo

29. dimermonomers 12 discrete Petri net 11 1 1 hybrid dynamic net 12 hybrid functional Petri net describe naturally explosion of tokens Not intuitive nor natural © Copyright 2002 Satoru Miyano, Human Genome Center, University of Tokyo

30. Lambda phage genetic switch feedback mecnanism

31. 1. Identify main events in the biopathway of concern. places 2. places : Continuous places (doubled circles) ： contain real numbers which represent concentrations of mRNA and Proteins. Discrete places (single circles) ： are corresponded to the promoter or operator sites for expressing the binding situation of transcription factor Design of hybrid functional Petri net

32. transitions3. transitions: interactions between objects –hidden interaction should also be identified functions4. functions assigned to transitions : –based on the logical structure in events and biological/biochemical knowledge about objects 5. Simulate, evaluate, and tune up the designed HFPN transition 3. transition : Continuous transitions (white rectangles) ： are used for expressing the production/degradation speed of mRNAs or proteins. Discrete transitions (black rectangles) ： are used for expressing the required time for RNA polymerase which moves between two genes. Design of hybrid functional Petri net

35. XML Integration of Biopathway in Genomic Object Net in Genomic Object Net

36. m1m2 T1 1m1/2 P1P2 m1/2.5 XML representation of HFPN

38. XML Biopathway Visualization (Upper left) Lambda phage chromosome –brightness or color of gene is changed according to the protein concentration level (upper right) Concentrations of proteins N and CI –Direct display of csv file in Simulation Result Files (bottom) CI and Cro binding to O R 1, O R 2, O R 3

39. Conclusion The HFPN model for representing and simulating biopathways. XML documents for description and visualization of HFPN together with simulation results. The future plan of Genomic Object Net is to construct a knowledge database of biopathways which allow computer simulation and visualization.

40. Result For all biochemical passways are hard to modeling in a good mathematical Knowledge

41. http://www.GenomicObject.Net

42. Thank you for your attention Thank you for your attention