Neural network aided approximation and parameterinference of stochastic models of gene expression

Abstract

Non-Markov models of stochastic biochemical kinetics often incorporate explicit time delays to effectively model large numbers of intermediate biochemical processes. Analysis and simulation of these models, as well as the inference of their parameters from data, are fraught with difficulties because the dynamics depends on the systems history. Here we use an artificial neural network to approximate the time-dependent distributions of non-Markov models by the solutions of much simpler time-inhomogeneous Markov models; the approximation does not increase the dimensionality of the model and simultaneously leads to inference of the kinetic parameters. The training of the neural network uses a relatively small set of noisy measurements generated by experimental data or stochastic simulations of the non-Markov model. We show using a variety of models, where the delays stem from transcriptional processes and feedback control, that the Markov models learnt by the neural network accurately reflect the stochastic dynamics across parameter space.