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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Danos, V., Feret, J., Fontana, W., Harmer, R., Krivine, J. (2009). Rule-Based Modelling and Model Perturbation. In: Priami, C., Back, RJ., Petre, I. (eds) Transactions on Computational Systems Biology XI. Lecture Notes in Computer Science(), vol 5750. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04186-0_6
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DOI: https://doi.org/10.1007/978-3-642-04186-0_6
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