Background: We address the problem of determining the controllability and accessibility of nonlinear biosystems. We consider models described by affine-in-inputs ordinary differential equations, which are adequate for a wide array of biological processes. Roughly speaking, the controllability of a dynamical system determines the possibility of steering it from an initial state to any point in its neighbourhood; accessibility is a weaker form of controllability.
Methods: While the methodology for analysing the controllability of linear systems is well established, its generalization to the nonlinear case has proven elusive. Thus, a number of related but different properties - including different versions of accessibility, reachability or weak local controllability - have been defined to approach its study, and several partial results exist in lieu of a general test. Here, leveraging the applicable results from differential geometric control theory, we source sufficient conditions to assess nonlinear controllability, as well as a necessary and sufficient condition for accessibility.
Results: We develop an algorithmic procedure to evaluate these conditions efficiently, and we provide its open source implementation. Using this software tool, we analyse the accessibility and controllability of a number of models of biomedical interest. While some of them are fully controllable, we find others that are not, as is the case of some models of EGF and NFκB signalling networks.
Conclusions: The contributions in this paper facilitate the accessibility and controllability analysis of nonlinear models, not only in biomedicine but also in other areas in which they have been rarely performed to date.
Keywords: Accessibility; Computational methods; Controllability; Modeling; Signalling pathways.
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.