Generating Stochastic Gene Regulatory Networks Consistent With Pathway Information and Steady-State Behavior

Abstract

We present a procedure to generate a stochastic genetic regulatory network model consistent with pathway information. Using the stochastic dynamics of Markov chains, we produce a model constrained by the prior knowledge despite the sometimes incomplete, time independent, and often conflicting nature of these pathways. We apply the Markov theory to study the model's long run behavior and introduce a biologically important transformation to aid in comparison with real biological outcome prediction in the steady-state domain. Our technique produces biologically faithful models without the need for rate kinetics, detailed timing information, or complex inference procedures. To demonstrate the method, we produce a model using 28 pathways from the biological literature pertaining to the transcription factor family nuclear factor-κB. Predictions from this model in the steady-state domain are then validated against nine mice knockout experiments.