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Modeling of Signaling Pathways Based on Petri nets Hiroshi Matsuno Graduate School of Science and Engineering Yamaguchi University International Symposium.

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Presentation on theme: "Modeling of Signaling Pathways Based on Petri nets Hiroshi Matsuno Graduate School of Science and Engineering Yamaguchi University International Symposium."— Presentation transcript:

1 Modeling of Signaling Pathways Based on Petri nets Hiroshi Matsuno Graduate School of Science and Engineering Yamaguchi University International Symposium on Symbolic Systems Biology (ISSSB11) Shonan Village Center November, 2011

2 July 4-9, 2004

3 Petri nets process algebra π-calculus timed automata probabilistic automata finite state linear model differential equations rule based model Boolean model Feb 22-27, 2009

4 1… 2… 3 Isolated paradise with no distractions Merits of NII Shonan Meeting

5 Petri nets Symbolic representation of systems in graphical manner... In the aims of this meeting … A secondary aim is to identify ways purely symbolic methods have been or could be combined with numerical techniques and applied to emerging problems in experimental and synthetic biology.

6 Hybrid Petri Net

7 tank flow off flow on lever Example of hybrid Petri net

8 Lambda phage genetic switch feedback mechanism

9

10 Simulation on Cell Illustrator

11 Signaling pathways stimulus cell membrane enzyme 1 cell nuclei To control proliferation, differentiation, and life of cells Information transmission from cell membrane to cell nuclei by the cascade of enzymes enzyme 2 enzyme n

12 signaling pathway components

13 Petri net model inactive JNK MEK4,7... inactive Elk-1 inactive MEK4,7 a part of signaling pathway... MEK4,7 JNK MEK4,7... Elk-1 Activation Transduction Component (ATC) A set of reactions influenced by an enzyme

14 A part of signaling pathway... MEK4,7 JNK MEK4,7... Elk-1 Petri net model inactive JNK MEK4,7... inactive Elk-1 inactive MEK4,7 ATCATC Elementary T-invariant ATC = Elementary T-invariant Signaling Pathway TERM Petri net TERM

15 Algorithm to find ATC C. Li, S. Suzuki, Q.-W.Ge, M. Nakata, H. Matsuno, S. Miyano, Structural modeling and analysis of signaling pathways based on Petri nets, J. Bioinfo. Comput. Biol. 4(5), pp ,

16 An Example of signaling pathway modeling G protein signaling pathways outside of a cell inside of a cell Adenylyl cyclase pathway Ras-MAPK pathway PLC pathway

17 Petri net model of G protein signaling pathway Petri net model of signaling pathway G protein signaling pathway Ras-MAPK pathway PLC pathway Adenylyl cyclase pathway

18 ATC-based decomposition of signaling pathway G protein signaling pathway N 1 N 2 N 3

19 Result of the decomposition signal flow representation timed Petri net

20 ATC representation of pathway N 1 N 2 N 3 N 4 N 5 N 6 N 7 N 8 N 9 N 10 N 11 N 12 N 13 N 14 N 15 N 16 N 17 Subnet N 9 (MEK activation by Raf-1) is an important reaction in the pathway. More than one pathways are working for producing the same gene product. Ras-MAPK pathway PLC pathway Adenylyl cyclase pathway Easy to acquire the characteristics on the structure of signaling pathways

21 careful three structures of Petri net tItI 1 tItI 2 tOtO β 1 β m α 1 α n α 2 synchronize p tItI 1 tItI m tOtO 1 β 1 β m tOtO n α 1 α n α 2 tOtO 2 s1s1 s2s2 snsn conflict t2t2 t1t1 t3t3 t4t4 t5t5 α2α2 β1β1 β2β2 β3β3 α5α5 β5β5 α 3-1 α4α4 α 3-2 p1p1 p2p2 p3p3 p4p4 acyclic can be used for parameter estimation

22 Conclusion and future work I am very happy to be here, --- Dagstuhl style meeting in Asia. Delay time determination of transitions for representing signal flow dynamics based on the structure of the Petri net model and experimentally obtained data. Qualitative characterization of signaling pathways for biological and medical applications

23 Collaborators in Yamaguchi Univ. Petri net modeling Qi-Wei Ge Yuki Murakami Experimental data of signaling components using cell array system Tomoko Furuya This research is partially supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (B).


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