A general computational method for robustness analysis with applications to synthetic gene networks.
BACKGROUND
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.


BACKGROUND
Version 2.8 of BIOCHAM and the transcriptional cascade model are available at http://contraintes.inria.fr/BIOCHAM/.
Rizk
Aurélien
A
INRIA Paris-Rocquencourt, 78153 Le Chesnay Cedex, France.
Batt
Gregory
G
Fages
François
F
Soliman
Sylvain
S
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics*; D012984:Software