A non-homogeneous dynamic Bayesian network with sequentially coupled interaction parameters for applications in systems and synthetic biology

An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional homogeneous DBNs fail to model the non-stationarity and time-varying nature of the gene regulatory processes. Various authors have therefore recently proposed combining DBNs with multiple changepoint processes to obtain time varying dynamic Bayesian networks (TV-DBNs). However, TV-DBNs are not without problems. Gene expression time series are typically short, which leaves the model over-flexible, leading to over-fitting or inflated inference uncertainty. In the present paper, we introduce a Bayesian regularization scheme that addresses this difficulty. Our approach is based on the rationale that changes in gene regulatory processes appear gradually during an organism's life cycle or in response to a changing environment, and we have integrated this notion in the prior distribution of the TV-DBN parameters. We have extensively tested our regularized TV-DBN model on synthetic data, in which we have simulated short non-homogeneous time series produced from a system subject to gradual change. We have then applied our method to real-world gene expression time series, measured during the life cycle of Drosophila melanogaster, under artificially generated constant light condition in Arabidopsis thaliana, and from a synthetically designed strain of Saccharomyces cerevisiae exposed to a changing environment

Fast MCMC sampling for Markov jump processes and extensions

Markov jump processes (or continuous-time Markov chains) are a simple and important class of continuous-time dynamical systems. In this paper, we tackle the problem of simulating from the posterior distribution over paths in these models, given partial and noisy observations. Our approach is an auxiliary variable Gibbs sampler, and is based on the idea of uniformization. This sets up a Markov chain over paths by alternately sampling a finite set of virtual jump times given the current path and then sampling a new path given the set of extant and virtual jump times using a standard hidden Markov model forward filtering-backward sampling algorithm. Our method is exact and does not involve approximations like time-discretization. We demonstrate how our sampler extends naturally to MJP-based models like Markov-modulated Poisson processes and continuous-time Bayesian networks and show significant computational benefits over state-of-the-art MCMC samplers for these models.Comment: Accepted at the Journal of Machine Learning Research (JMLR

Exact ICL maximization in a non-stationary temporal extension of the stochastic block model for dynamic networks

The stochastic block model (SBM) is a flexible probabilistic tool that can be used to model interactions between clusters of nodes in a network. However, it does not account for interactions of time varying intensity between clusters. The extension of the SBM developed in this paper addresses this shortcoming through a temporal partition: assuming interactions between nodes are recorded on fixed-length time intervals, the inference procedure associated with the model we propose allows to cluster simultaneously the nodes of the network and the time intervals. The number of clusters of nodes and of time intervals, as well as the memberships to clusters, are obtained by maximizing an exact integrated complete-data likelihood, relying on a greedy search approach. Experiments on simulated and real data are carried out in order to assess the proposed methodology