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

Constructing non-stationary Dynamic Bayesian Networks with a flexible lag choosing mechanism

Background Dynamic Bayesian Networks (DBNs) are widely used in regulatory network structure inference with gene expression data. Current methods assumed that the underlying stochastic processes that generate the gene expression data are stationary. The assumption is not realistic in certain applications where the intrinsic regulatory networks are subject to changes for adapting to internal or external stimuli. Results In this paper we investigate a novel non-stationary DBNs method with a potential regulator detection technique and a flexible lag choosing mechanism. We apply the approach for the gene regulatory network inference on three non-stationary time series data. For the Macrophages and Arabidopsis data sets with the reference networks, our method shows better network structure prediction accuracy. For the Drosophila data set, our approach converges faster and shows a better prediction accuracy on transition times. In addition, our reconstructed regulatory networks on the Drosophila data not only share a lot of similarities with the predictions of the work of other researchers but also provide many new structural information for further investigation. Conclusions Compared with recent proposed non-stationary DBNs methods, our approach has better structure prediction accuracy By detecting potential regulators, our method reduces the size of the search space, hence may speed up the convergence of MCMC sampling

Constructing non-stationary Dynamic Bayesian Networks with a flexible lag choosing mechanism

Background: Dynamic Bayesian Networks (DBNs) are widely used in regulatory network structure inference with gene expression data. Current methods assumed that the underlying stochastic processes that generate the gene expression data are stationary. The assumption is not realistic in certain applications where the intrinsic regulatory networks are subject to changes for adapting to internal or external stimuli. Results: In this paper we investigate a novel non-stationary DBNs method with a potential regulator detection technique and a flexible lag choosing mechanism. We apply the approach for the gene regulatory network inference on three non-stationary time series data. For the Macrophages and Arabidopsis data sets with the reference networks, our method shows better network structure prediction accuracy. For the Drosophila data set, our approach converges faster and shows a better prediction accuracy on transition times. In addition, our reconstructed regulatory networks on the Drosophila data not only share a lot of similarities with the predictions of the work of other researchers but also provide many new structural information for further investigation. Conclusions: Compared with recent proposed non-stationary DBNs methods, our approach has better structure prediction accuracy By detecting potential regulators, our method reduces the size of the search space, hence may speed up the convergence of MCMC sampling

Constructing non-stationary Dynamic Bayesian Networks with a flexible lag choosing mechanism

<p>Abstract</p> <p>Background</p> <p>Dynamic Bayesian Networks (DBNs) are widely used in regulatory network structure inference with gene expression data. Current methods assumed that the underlying stochastic processes that generate the gene expression data are stationary. The assumption is not realistic in certain applications where the intrinsic regulatory networks are subject to changes for adapting to internal or external stimuli.</p> <p>Results</p> <p>In this paper we investigate a novel non-stationary DBNs method with a potential regulator detection technique and a flexible lag choosing mechanism. We apply the approach for the gene regulatory network inference on three non-stationary time series data. For the Macrophages and Arabidopsis data sets with the reference networks, our method shows better network structure prediction accuracy. For the Drosophila data set, our approach converges faster and shows a better prediction accuracy on transition times. In addition, our reconstructed regulatory networks on the Drosophila data not only share a lot of similarities with the predictions of the work of other researchers but also provide many new structural information for further investigation.</p> <p>Conclusions</p> <p>Compared with recent proposed non-stationary DBNs methods, our approach has better structure prediction accuracy By detecting potential regulators, our method reduces the size of the search space, hence may speed up the convergence of MCMC sampling.</p

Learning from Neighbors about a Changing State

Agents learn about a changing state using private signals and past actions of neighbors in a network. We characterize equilibrium learning and social influence in this setting. We then examine when agents can aggregate information well, responding quickly to recent changes. A key sufficient condition for good aggregation is that each individual's neighbors have sufficiently different types of private information. In contrast, when signals are homogeneous, aggregation is suboptimal on any network. We also examine behavioral versions of the model, and show that achieving good aggregation requires a sophisticated understanding of correlations in neighbors' actions. The model provides a Bayesian foundation for a tractable learning dynamic in networks, closely related to the DeGroot model, and offers new tools for counterfactual and welfare analyses.Comment: minor revision tweaking exposition relative to v5 - which added new Section 3.2.2, new Theorem 2, new Section 7.1, many local revision

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