The circuit-breaking algorithm for monotone systems (Q503861)

This paper details the use of the circuit-breaking algorithm (CBA), an approach which uses the interaction graph of a given biochemical regulatory network to output an one-dimensional circuit characteristic for which the zeroes correspond to the fixed points of the system, for the stability analysis of monotone systems. The stability of a given fixed point is expressed in terms of the slope of the circuit characteristic, being observed that a positive slope of this characteristic implies the instability of the respective fixed point provided that the open loop system (OLS) is globally asymptotically stable and has a nondegenerate input-to-state characteristic, while a negative slope implies asymptotic stability if, additionally, the original system is monotone. The stability results are specialized and commented for two concrete examples, a \(6\)-dimensional model for differentiation of hematopoietic stem cells and a \(5\)-dimensional model of the mitogen-activated protein kinase (MAPK) signalling pathway, for which the long-term behaviour of the solutions is completely characterized. Further, the authors highlight the specific differences between CBA and the approach of \textit{D. Angeli} and \textit{E. D. Sontag} [Syst. Control Lett. 51, No. 3--4, 185--202 (2004; Zbl 1157.93509)], while also stressing the importance of the nondegeneracy of the OLS and outlining several directions of further work.