TY - JOUR T1 - A general computational method for robustness analysis with applications to synthetic gene networks AU - Rizk, Aurélien AU - Batt, Gregory AU - Fages, François AU - Soliman, Sylvain Y1 - 2009/06/15 N1 - 10.1093/bioinformatics/btp200 JO - Bioinformatics SP - i169 EP - i178 VL - 25 IS - 12 N2 - 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 SN - 1367-4803 M3 - doi: 10.1093/bioinformatics/btp200 UR - http://dx.doi.org/10.1093/bioinformatics/btp200 ER -