Understanding signalling networks as collections of signal transduction pathways
Proceedings of the 8th International Conference on Computational Methods in Systems Biology
A language for biochemical systems: design and formal specification
Transactions on Computational Systems Biology XII
Quantitative Model Refinement as a Solution to the Combinatorial Size Explosion of Biomodels
Electronic Notes in Theoretical Computer Science (ENTCS)
The Phosphorylation of the Heat Shock Factor as a Modulator for the Heat Shock Response
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
BMA: visual tool for modeling and analyzing biological networks
CAV'12 Proceedings of the 24th international conference on Computer Aided Verification
Spatial modeling in cell biology at multiple levels
Proceedings of the Winter Simulation Conference
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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.