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Approximate Bayesian Computation is widely used in systems biology for inferring parameters in stochastic gene regulatory network models. Its performance hinges critically on the ability to summarize high-dimensional system responses such as time series into a few informative, low-dimensional summary statistics. The quality of those statistics acutely impacts the accuracy of the inference task. Existing methods to select the best subset out of a pool of candidate statistics do not scale well with large pools of several tens to hundreds of candidate statistics. Since high quality statistics are imperative for good performance, this becomes a serious bottleneck when performing inference on complex and high-dimensional problems.This paper proposes a convolutional neural network architecture for automatically learning informative summary statistics of temporal responses. We show that the proposed network can effectively circumvent the statistics selection problem of the preprocessing step for ABC inference. The proposed approach is demonstrated on two benchmark problem and one challenging inference problem learning parameters in a high-dimensional stochastic genetic oscillator. We also study the impact of experimental design on network performance by comparing different data richness and data acquisition strategies.

State-of-the-art neural network-based methods for learning summary statistics have delivered promising results for simulation-based likelihood-free parameter inference. Existing approaches for learning summarizing networks are mainly based on deterministic neural networks, and do not take network prediction uncertainty into account. This work proposes a robust integrated approach that learns summary statistics using Bayesian neural networks, and produces a proposal posterior density using categorical distributions. An adaptive sampling scheme selects simulation locations to efficiently and iteratively refine the predictive proposal posterior of the network conditioned on observations. This allows for more efficient and robust convergence on comparatively large prior spaces. The approximated proposal posterior can then either be processed through a correction mechanism, or be used in conjunction with a density estimator to arrive at the true posterior. We demonstrate our approach on benchmark examples.

Discrete stochastic models of gene regulatory networks are fundamental tools for in silico study of stochastic gene regulatory networks. Likelihood-free inference and model exploration are critical applications to study a system using such models. However, the massive computational cost of complex, high-dimensional and stochastic modelling currently limits systematic investigation to relatively simple systems. Recently, machine-learning-assisted methods have shown great promise to handle larger, more complex models. To support both ease-of-use of this new class of methods, as well as their further development, we have developed the scalable inference, optimization and parameter exploration (Sciope) toolbox. Sciope is designed to support new algorithms for machine-learning-assisted model exploration and likelihood-free inference. Moreover, it is built ground up to easily leverage distributed and heterogeneous computational resources for convenient parallelism across platforms from workstations to clouds.The Sciope Python3 toolbox is freely available on https://github.com/Sciope/Sciope, and has been tested on Linux, Windows and macOS platforms.Supplementary information is available at Bioinformatics online.

We present StochSS Live!, a web-based service for modeling, simulation and analysis of a wide range of mathematical, biological and biochemical systems. Using an epidemiological model of COVID-19, we demonstrate the power of StochSS Live! to enable researchers to quickly develop a deterministic or a discrete stochastic model, infer its parameters and analyze the results.StochSS Live! is freely available at https://live.stochss.org/Supplementary data are available at Bioinformatics online.