Bounded noise induced first-order phase transitions in a baseline non-spatial model of gene transcription

3In this work we consider, from a statistical mechanics point of view, the effects of bounded stochastic perturbations of the protein decay rate for a bistable biomolecular network module. Namely, we consider the perturbations of the protein decay/binding rate constant (DBRC) in a circuit modeling the positive feedback of a transcription factor (TF) on its own synthesis. The DBRC models both the spontaneous degradation of the TF and its linking to other unknown biomolecular factors or drugs. We show that bounded perturbations of the DBRC preserve the positivity of the parameter value (and also its limited variation), and induce effects of interest. First, the noise amplitude induces a first-order phase transition. This is of interest since the system in study has neither spatial components nor it is composed by multiple interacting networks. In particular, we observe that the system passes from two to a unique stochastic attractor, and vice-versa. This behavior is different from noise-induced transitions (also termed phenomenological bifurcations), where a unique stochastic attractor changes its shape depending on the values of a parameter. Moreover, we observe irreversible jumps as a consequence of the above-mentioned phase transition. We show that the illustrated mechanism holds for general models with the same deterministic hysteresis bifurcation structure. Finally, we illustrate the possible implications of our findings to the intracellular pharmacodynamics of drugs delivered in continuous infusion. (C) 2017 Elsevier B.V. All rights reserved.reservedmixedd'Onofrio A; Caravagna G; de Franciscis SD'Onofrio, A; Caravagna, G; de Franciscis, S; D'Onofrio, Albert