CRITERIA: A network decomposition and elementary flux mode translation-based tool for computing equilibria of biochemical systems

Abstract

Understanding how biochemical systems settle into stable states, such as how protein concentrations reach equilibrium, is central to explaining cellular behavior and designing synthetic biological circuits. However, existing analytical tools for computing these equilibria, such as COMPILES, are limited by computational bottlenecks and can only be applied to a restricted class of reaction networks. In this work, we introduce CRITERIA (Computing paRametrized posITive EquilibRIA), a new computational framework that makes equilibrium analysis more efficient and broadly applicable. CRITERIA uses a graph-based approach built on elementary flux modes to streamline key steps in the computation. It also changes how the problem is solved by combining subnetworks into a single system before computing equilibria, which avoids complicated symbolic calculations required in previous methods. We demonstrate the usefulness of CRITERIA by studying biologically important systems, including the EnvZ-OmpR signaling pathway and a synthetic CRISPRi circuit. Our approach enables faster and more scalable analysis, allowing researchers to better understand how complex biochemical networks behave over time.