Bayesian regularization of hidden Markov models with an application to bioinformatics

This paper discusses a Bayesian approach to regularizing hidden Markov models and demonstrates an application of this scheme to Bioinformatics

Reverse engineering of genetic networks with Bayesian networks

This paper provides a brief introduction to learning Bayesian networks from gene-expression data. The method is contrasted with other approaches to the reverse engineering of biochemical networks, and the Bayesian learning paradigm is briefly described. The article demonstrates an application to a simple synthetic toy problem and evaluates the inference performance in terms of ROC (receiver operator characteristic) curves

Bayesian regularization of non-homogeneous dynamic Bayesian networks by globally coupling interaction parameters

To relax the homogeneity assumption of classical dynamic Bayesian networks (DBNs), various recent studies have combined DBNs with multiple changepoint processes. The underlying assumption is that the parameters associated with time series segments delimited by multiple changepoints are a priori independent. Under weak regularity conditions, the parameters can be integrated out in the likelihood, leading to a closed-form expression of the marginal likelihood. However, the assumption of prior independence is unrealistic in many real-world applications, where the segment-specific regulatory relationships among the interdependent quantities tend to undergo gradual evolutionary adaptations. We therefore propose a Bayesian coupling scheme to introduce systematic information sharing among the segment-specific interaction parameters. We investigate the effect this model improvement has on the network reconstruction accuracy in a reverse engineering context, where the objective is to learn the structure of a gene regulatory network from temporal gene expression profiles

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

Assessing the impact of non-additive noise on modelling transcriptional regulation with Gaussian processes

In transcriptional regulation, transcription factors (TFs) are often unobservable at mRNA level or may be controlled outside of the system being modelled. Gaussian processes are a promising approach for dealing with these difficulties as a prior distribution can be defined over the latent TF activity profiles and the posterior distribution inferred from the observed expression levels of potential target genes. However previous approaches have been based on the assumption of additive Gaussian noise to maintain analytical tractability. We investigate the influence of a more realistic form of noise on a biologically accurate system based on Michaelis-Menten kinetics

Dynamic Bayesian networks in molecular plant science: inferring gene regulatory networks from multiple gene expression time series

To understand the processes of growth and biomass production in plants, we ultimately need to elucidate the structure of the underlying regulatory networks at the molecular level. The advent of high-throughput postgenomic technologies has spurred substantial interest in reverse engineering these networks from data, and several techniques from machine learning and multivariate statistics have recently been proposed. The present article discusses the problem of inferring gene regulatory networks from gene expression time series, and we focus our exposition on the methodology of Bayesian networks. We describe dynamic Bayesian networks and explain their advantages over other statistical methods. We introduce a novel information sharing scheme, which allows us to infer gene regulatory networks from multiple sources of gene expression data more accurately. We illustrate and test this method on a set of synthetic data, using three different measures to quantify the network reconstruction accuracy. The main application of our method is related to the problem of circadian regulation in plants, where we aim to reconstruct the regulatory networks of nine circadian genes in Arabidopsis thaliana from four gene expression time series obtained under different experimental conditions

Inference in complex biological systems with Gaussian processes and parallel tempering

Parameter inference in mathematical models of complex biological systems, expressed as coupled ordinary differential equations (ODEs), is a challenging problem. These depend on kinetic parameters, which cannot all be measured and have to be ascertained a different way. However, the computational costs associated with repeatedly solving the ODEs are often staggering, making many techniques impractical. Therefore, aimed at reducing this cost, new concepts using gradient matching have been proposed. This paper combines current adaptive gradient matching approaches, using Gaussian processes, with a parallel tempering scheme, in order to compare 2 different paradigms using the same nonlinear regression method. We use 2 ODE systems to assess our technique, showing an improvement over the recent method in Calderhead et al. (2008)

Heterogeneous continuous dynamic Bayesian networks with flexible structure and inter-time segment information sharing

Classical dynamic Bayesian networks (DBNs) are based on the homogeneous Markov assumption and cannot deal with heterogeneity and non-stationarity in temporal processes. Various approaches to relax the homogeneity assumption have recently been proposed. The present paper aims to improve the shortcomings of three recent versions of heterogeneous DBNs along the following lines: (i) avoiding the need for data discretization, (ii) increasing the flexibility over a time-invariant network structure, (iii) avoiding over-flexibility and overfitting by introducing a regularization scheme based in inter-time segment information sharing. The improved method is evaluated on synthetic data and compared with alternative published methods on gene expression time series from Drosophila melanogaster. 1

Detecting mosaic structures in DNA sequence alignments

This article first provides a concise introduction to the statistical approach to phyloge- netics. It then describes a new method for detecting mosaic structures in DNA sequence alignments, which is based on combining two probabilistic graphical models: (1) a taxon graph (phylogenetic tree) representing the relationships among the taxa, and (2) a site graph (hidden Markov model) representing spatial correlations between nucleotides