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Rule-Based Modelling and Model Perturbation

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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https://hal.inria.fr/inria-00528364
Contributor : Jérôme Feret Connect in order to contact the contributor
Submitted on : Thursday, October 21, 2010 - 4:23:28 PM
Last modification on : Thursday, March 17, 2022 - 10:08:35 AM

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Vincent Danos, Jérôme Feret, Walter Fontana, Russ Harmer, Jean Krivine. Rule-Based Modelling and Model Perturbation. Transactions on Computational Systems Biology, Springer, 2009, Transactions on Computational Systems Biology XI, 5750, pp.116-137. ⟨10.1007/978-3-642-04186-0_6⟩. ⟨inria-00528364⟩

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