Derivation of stationary distributions of biochemical reaction networks via structure transformation

• DOI: 10.1038/s42003-021-02117-x
• Publication Date: 2021-05-24T10:03:09Z
• Authors: Hyukpyo Hong; Jinsu Kim; M. Ali Al-Radhawi; Eduardo D. Sontag; Jae Kyoung Kim
• Keywords: 0301 basic medicine; QH301-705.5; 612; Models, Biological; Article; Cell Physiological Phenomena; 03 medical and health sciences; SYSTEMS; Aurora Kinase B; Humans; Biology (General); KINETICS; Stochastic Processes; 0303 health sciences; COMPLEX; 9. Industry and infrastructure; Computational Biology; DEGRADATION; MODEL; ErbB Receptors; p21-Activated Kinases; PAK1; Algorithms; Metabolic Networks and Pathways

AbstractLong-term behaviors of biochemical reaction networks (BRNs) are described by steady states in deterministic models and stationary distributions in stochastic models. Unlike deterministic steady states, stationary distributions capturing inherent fluctuations of reactions are extremely difficult to derive analytically due to the curse of dimensionality. Here, we develop a method to derive analytic stationary distributions from deterministic steady states by transforming BRNs to have a special dynamic property, called complex balancing. Specifically, we merge nodes and edges of BRNs to match in- and out-flows of each node. This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity, and multi-modality. Importantly, we provide a user-friendly computational package, CASTANET, that automatically derives symbolic expressions of the stationary distributions of BRNs to understand their long-term stochasticity.