Simulation of Kohn’s Molecular Interaction Maps through Translation into Stochastic CLS+

  • Roberto Barbuti
  • Daniela Lepri
  • Andrea Maggiolo-Schettini
  • Paolo Milazzo
  • Giovanni Pardini
  • Aureliano Rama
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5947)


Kohn’s Molecular Interaction Maps (MIMs) are a graphical notation for describing bioregulatory networks at the molecular level. Even if the meaning of Kohn’s diagrams can be often easily understood, in many cases, due to the lack of a precise mathematical semantics, the notation can be ambiguous. By this paper we achieve two goals. Firstly, we give a precise meaning to MIMs by their translation into a formalism, the Stochastic Calculus of Looping Sequences (SCLS+), with a mathematical semantics. Further, by this translation we provide MIMs with all the tools developed for SCLS+, namely analysers and simulators. The ability of SCLS+ to specify compartments allows us to easily translate MIMs descriptions also when membranes are involved in the interactions.


Parallel Composition Loop Sequence Continuous Time Markov Chain Biochemical Network Graphical Notation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aladjem, M.I., Pasa, S., Parodi, S., Weinstein, J.N., Pommier, Y., Kohn, K.W.: Molecular Interaction Maps–A Diagrammatic Graphical Language for Bioregulatory Networks. Sci. STKE 2004 (222), 8 (2004)Google Scholar
  2. 2.
    Kohn, K.W.: Molecular Interaction Maps as Information Organizers and Simulation Guides. CHAOS 11(1), 84–97 (2001)zbMATHCrossRefGoogle Scholar
  3. 3.
    Kohn, K.W., Aladjem, M.I., Weinstein, J.N., Pommier, Y.: Molecular Interaction Maps of Bioregulatory Networks: A General Rubric for Systems Biology. Molecular Biology of the Cell 17, 1–13 (2006)CrossRefGoogle Scholar
  4. 4.
    Barbuti, R., Maggiolo-Schettini, A., Milazzo, P., Tiberi, P., Troina, A.: Stochastic CLS for the Modeling and Simulation of Biological Systems. Trans. on Comput. Syst. Biol. IX 5121, 86–113 (2008)CrossRefGoogle Scholar
  5. 5.
    Milazzo, P.: Qualitative and Quantitative Formal Modeling of Biological Systems. PhD thesis, Computer Science Department - University of Pisa (2007)Google Scholar
  6. 6.
    Milazzo, P.: Formal Modeling in Systems Biology. An approach from Theoretical Computer Science. VDM - Verlag Dr. Muller, Saarbrucken (2008)Google Scholar
  7. 7.
    Ciocchetta, F., Priami, C., Quaglia, P.: Modeling Kohn Interaction Maps with Beta-Binders: An Example. Trans. on Comput. Syst. Biol. III 3737, 33–48 (2005)CrossRefMathSciNetGoogle Scholar
  8. 8.
    Priami, C., Quaglia, P.: Beta Binders for Biological Interactions. In: Danos, V., Schachter, V. (eds.) CMSB 2004. LNCS (LNBI), vol. 3082, pp. 20–33. Springer, Heidelberg (2005)CrossRefGoogle Scholar
  9. 9.
    Bortolussi, L., Fonda, S., Policriti, A.: Constraint-Based Simulation of Biological Systems Described by Molecular Interaction Maps. In: IEEE International Conference on Bioinformatics and Biomedicine, vol. 0, pp. 288–293 (2007)Google Scholar
  10. 10.
    Kitano, H.: A Graphical Notation for Biochemical Networks. BIOSILICO 1(5), 169–176 (2003)CrossRefGoogle Scholar
  11. 11.
    Pirson, I., Fortemaison, N., Jacobs, C., Dremier, S., Dumont, J.E., Maenhaut, C.: The Visual Display of Regulatory Information and Networks. Trends in Cell Biology 10, 404–408 (2000)CrossRefGoogle Scholar
  12. 12.
    Systems Biology Graphical Notation,
  13. 13.
    Kohn, K.W., Aladjem, M.I.: Circuit Diagrams for Biological Networks. Molecular Systems Biology 2 (2006)Google Scholar
  14. 14.
    Oda, K., Matsuoka, Y., Funahashi, A., Kitano, H.: A Comprensive Pathway Map of Epidermal Growth Factor Receptor Signaling. Molecular Systems Biology 1 (2005)Google Scholar
  15. 15.
    Funahashi, A., Morohashi, M., Kitano, H.: CellDesigner: a Process Diagram Editor for Gene–Regulatory and Biochemical Networks. BIOSILICO 1(5), 159–162 (2003)CrossRefGoogle Scholar
  16. 16.
    Danos, V., Laneve, C.: Formal molecular biology. Theor. Comp. Sci. 325(1), 69–110 (2004)zbMATHCrossRefMathSciNetGoogle Scholar
  17. 17.
    Faeder, J.R., Blinov, M.L., Hlavacek, W.S.: Graphical rule-based representation of signal-transduction networks. In: Symposium on Applied Computing (SAC), pp. 133–140 (2005)Google Scholar
  18. 18.
    Lepri, D.: A formal semantics for Molecular Interaction Maps. Master Thesis in Computer Science, University of Pisa (2008)Google Scholar
  19. 19.
    Gillespie, D.T.: Exact stochastic simulation of coupled chemical reactions. Journal of Physical Chemistry 81(25), 2340–2361 (1977)CrossRefGoogle Scholar
  20. 20.

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Roberto Barbuti
    • 1
  • Daniela Lepri
    • 2
  • Andrea Maggiolo-Schettini
    • 1
  • Paolo Milazzo
    • 1
  • Giovanni Pardini
    • 1
  • Aureliano Rama
    • 1
  1. 1.Dipartimento di InformaticaUniversità di Pisa 
  2. 2.Institutt for InformatikkUniversitetet i Oslo 

Personalised recommendations