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

Bioinformatics. 2009 Jun 15;25(12):i169-78. doi: 10.1093/bioinformatics/btp200.


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/.

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks / genetics*
  • Software