Computational framework NetBiF predicts and classifies steady-state bifurcations in biochemical systems via reaction network structure
Dynamics of biochemical systems are dictated by the stoichiometry and kinetics of reaction networks. These systems may admit positive steady states that could undergo qualitative change in response to varying rate parameters. These changes are called steady-state bifurcations, and they correspond to biologically meaningful processes. Classical bifurcation analysis relies on exact kinetics and rate parameters, which are often unknown or difficult to measure for complex systems. To address this, structural bifurcation analysis (SBA) was introduced to predict bifurcations using only the system's associated reaction network. In this work, the computational package NetBiF (Network Bifurcation Finder) is introduced to implement SBA. NetBiF is applied across diverse biochemical systems, including fundamental metabolic pathways, signaling and gene regulatory networks, and a large-scale carbon cycle model, to predict steady-state bifurcations. Crucially, for biochemical systems governed by power law kinetics, the implementation of NetBiF also classifies the steady-state bifurcations as saddle-node, transcritical, or pitchfork via a structural analog of Sotomayor's theorem. To this end, explicit formulations for the bifurcation criteria were derived for these biochemical systems. Determining and classifying bifurcation behaviors provide insight into biochemical systems' abilities to adapt to changing and fluctuating conditions. Collectively, the study presents NetBiF as a scalable, structure-based, and consistent computational tool to implement SBA. Our findings enable researchers to systematically study dynamical behaviors of biochemical systems through their reaction network structures without requiring explicit kinetic information.