Transactions on Computational Systems Biology XI pp 116-137

Part of the Lecture Notes in Computer Science book series (LNCS, volume 5750) | Cite as

Rule-Based Modelling and Model Perturbation

  • Vincent Danos
  • Jérôme Feret
  • Walter Fontana
  • Russ Harmer
  • Jean Krivine

Abstract

Rule-based modelling has already proved to be successful for taming the combinatorial complexity, typical of cellular signalling networks, caused by the combination of physical protein-protein interactions and modifications that generate astronomical numbers of distinct molecular species. However, traditional rule-based approaches, based on an unstructured space of agents and rules, remain susceptible to other combinatorial explosions caused by mutated and/or splice variant agents, that share most but not all of their rules with their wild-type counterparts; and by drugs, which must be clearly distinguished from physiological ligands.

In this paper, we define a syntactic extension of Kappa, an established rule-based modelling platform, that enables the expression of a structured space of agents and rules that allows us to express mutated agents, splice variants, families of related proteins and ligand/drug interventions uniformly. This also enables a mode of model construction where, starting from the current consensus model, we attempt to reproduce in numero the mutational—and more generally the ligand/drug perturbational—analyses that were used in the process of inferring those pathways in the first place.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Vincent Danos
    • 1
  • Jérôme Feret
    • 2
  • Walter Fontana
    • 3
  • Russ Harmer
    • 4
  • Jean Krivine
    • 3
    • 5
  1. 1.University of EdinburghUK
  2. 2.INRIA–ENS–CNRSFrance
  3. 3.Harvard Medical SchoolUSA
  4. 4.CNRS–Université Paris DiderotFrance
  5. 5.Institut des Hautes Etudes ScientifiquesFrance

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