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, advocated by Kitano [Mol Syst Biol, 3:137, 2007].
Results: In this paper, we propose a general definition of robustness
that applies to any biological function expressible in temporal logic
LTL, 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/