A new strategy for global uncertainty analysis of bistability in biomolecular systems

Nonlinear dynamical systems theory is a suited framework to describe and analyse, rigorously, cellular state transitions. The basic idea is to represent cellular states as attractors of dynamical systems. However, due to the inherent complexity of biological networks, there is a lack of general methods for the characterisation of the parameters and state spaces of these mathematical models. This work presents a novel approach, based on the combination of several nonlinear analysis techniques, for the investigation of biological bistable switches. A crucial feature of the proposed approach is the capability to perform a robust analysis, i.e. it can take into account the uncertainty of biochemical parameters (deriving from interindividual variability) and the intrinsic environmental noise (which causes fluctuations of the species concentrations).