A Decomposition-Based Approach for Deriving Positive Steady States of a Class of Chemical Reaction Networks with Non-Mass-Action Kinetics

Abstract

Steady states are frequently used to investigate the long-term behaviors of (bio)chemical systems. Recently, there has been a growing interest in network-based approaches due to their efficiency in deriving parametrizations of positive steady states in systems with mass-action kinetics. In this study, we extend this approach to derive positive steady states in networks under non-mass-action kinetics, specifically mixed kinetics. In a system with mixed kinetics, some reactions {may follow} mass-action kinetics, while others in the same network follow different rate laws, such as quotient rate laws. An example of such complexity is evident in a mathematical model of the insulin signaling pathway in type 2 diabetes. To compute its positive {steady states}, we adapt our existing network decomposition approach, originally designed for mass-action kinetics, to handle networks with non-mass-action kinetics. This approach involves breaking down a given network into smaller, independent subnetworks to derive the positive steady states of each subnetwork separately. These individual steady states are then combined to obtain the positive steady states of the entire network. This strategy makes computations more manageable for complex and large networks. More importantly, this method could separate reactions with purely mass-action kinetics into certain subnetworks from those that follow different rate laws. We also present an illustrative example that provides insights into methods for transforming networks with mixed kinetics into their associated mass-action systems.