Identifying dynamical bottlenecks of stochastic transitions in biochemical networks

In biochemical networks, identifying key proteins and protein-protein reactions that regulate fluctuation-driven transitions leading to pathological cellular function is an important challenge. Using large deviation theory, we develop a semianalytical method to determine how changes in protein expression and rate parameters of protein-protein reactions influence the rate of such transitions. Our formulas agree well with computationally costly direct simulations and are consistent with experiments. Our approach reveals qualitative features of key reactions that regulate stochastic transitions.