CMSB '09 Proceedings of the 7th International Conference on Computational Methods in Systems Biology
From model-checking to temporal logic constraint solving
CP'09 Proceedings of the 15th international conference on Principles and practice of constraint programming
On the use of temporal formal logic to model gene regulatory networks
CIBB'09 Proceedings of the 6th international conference on Computational intelligence methods for bioinformatics and biostatistics
On Parameter Synthesis by Parallel Model Checking
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
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Motivation: Robustness is the capacity of a system to maintain a function in the face of perturbations. It is essential for the correct functioning of natural and engineered biological systems. Robustness is generally defined in an ad hoc, problem-dependent manner, thus hampering the fruitful development of a theory of biological robustness, recently advocated by Kitano. Results: In this article, we propose a general definition of robustness that applies to any biological function expressible in temporal logic LTL (linear temporal logic), and to broad model classes and perturbation types. Moreover, we propose a computational approach and an implementation in BIOCHAM 2.8 for the automated estimation of the robustness of a given behavior with respect to a given set of perturbations. The applicability and biological relevance of our approach is demonstrated by testing and improving the robustness of the timed behavior of a synthetic transcriptional cascade that could be used as a biological timer for synthetic biology applications. Availability: Version 2.8 of BIOCHAM and the transcriptional cascade model are available at http://contraintes.inria.fr/BIOCHAM/ Contact: gregory.batt@inria.fr