Scalable Simulation of Cellular Signaling Networks

Abstract : Given the combinatorial nature of cellular signalling pathways, where biological agents can bind and modify each other in a large number of ways, concurrent or agent-based languages seem particularly suitable for their representation and simulation. Graphical modelling languages such as K, or the closely related BNG language, seem to afford particular ease of expression. It is unclear however how such models can be implemented. Even a simple model of the EGF receptor signalling network can generate more than 10^23 non-isomorphic species, and therefore no approach to simulation based on enumerating species (beforehand, or even on-the-fly) can handle such models without sampling down the number of potential generated species. We present in this paper a radically different method which does not attempt to count species. The proposed algorithm uses a representation of the system together with a super-approximation of its 'events horizon' (all events that may happen next), and a specific correction scheme to obtain exact timings. Being completely local and not based on any kind of enumeration, this algorithm has a per event time cost which is independent of (i) the size of the set of generable species (which can even be infinite), and (ii) independent of the size of the system (i.e. the number of agent instances). We show how to refine this algorithm, using concepts derived from the classical notion of causality, so that in addition to the above one also has that the event cost is depending (iii) only logarithmically on the size of the model (i.e. the number of rules). Such complexity properties reflect in our implementation which, on a current computer, generateste about 106 events per minute in the case of the simple EGF receptor model mentioned above, using a system with 105 agents.
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Communication dans un congrès
Shao, Z. the 5th Asian Symposium on Programming Languages and Systems - APLAS'07, Nov 2007, Singapore, Singapore. Springer, 4807, pp.139-157, 2007, Lecture Notes in Computer Science. 〈10.1.1.139.5120〉
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https://hal.inria.fr/inria-00528409
Contributeur : Jérôme Feret <>
Soumis le : jeudi 21 octobre 2010 - 16:33:30
Dernière modification le : jeudi 10 mai 2018 - 02:06:52

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Vincent Danos, Jérôme Feret, Walter Fontana, Jean Krivine. Scalable Simulation of Cellular Signaling Networks. Shao, Z. the 5th Asian Symposium on Programming Languages and Systems - APLAS'07, Nov 2007, Singapore, Singapore. Springer, 4807, pp.139-157, 2007, Lecture Notes in Computer Science. 〈10.1.1.139.5120〉. 〈inria-00528409〉

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