DNA hybridization arrays simultaneously measure the expression level for thousands of genes. These measurements provide a “snapshot ” of transcription levels within the cell. A major challenge in computational biology is to uncover, from such measurements, gene/protein interactions and key biological features of cellular systems. In this paper, we propose a new framework for discovering interactions between genes based on multiple expression measurements. This framework builds on the use of Bayesian networks for representing statistical dependencies. A Bayesian network is a graph-based model of joint multivariate probability distributions that captures properties of conditional independence between variables. Such models are attractive for their ability to describe complex stochastic processes and because they provide a clear methodology for learning from (noisy) observations. We start by showing how Bayesian networks can describe interactions between genes. We then describe a method for recovering gene interactions from microarray data using tools for learning Bayesian networks. Finally, we demonstrate this method on the S. cerevisiae cell-cycle measurements of Spellman et al. (1998). Key words: gene expression, microarrays, Bayesian methods. 1.

Modelling sequential data is important in many areas of science and engineering. Hidden Markov models (HMMs) and Kalman filter models (KFMs) are popular for this because they are simple and flexible. For example, HMMs have been used for speech recognition and bio-sequence analysis, and KFMs have been used for problems ranging from tracking planes and missiles to predicting the economy. However, HMMs and KFMs are limited in their “expressive power”. Dynamic Bayesian Networks (DBNs) generalize HMMs by allowing the state space to be represented in factored form, instead of as a single discrete random variable. DBNs generalize KFMs by allowing arbitrary probability distributions, not just (unimodal) linear-Gaussian. In this thesis, I will discuss how to represent many different kinds of models as DBNs, how to perform exact and approximate inference in DBNs, and how to learn DBN models from sequential data. In particular, the main novel technical contributions of this thesis are as follows: a way of representing Hierarchical HMMs as DBNs, which enables inference to be done in O(T) time instead of O(T 3), where T is the length of the sequence; an exact smoothing algorithm that takes O(log T) space instead of O(T); a simple way of using the junction tree algorithm for online inference in DBNs; new complexity bounds on exact online inference in DBNs; a new deterministic approximate inference algorithm called factored frontier; an analysis of the relationship between the BK algorithm and loopy belief propagation; a way of applying Rao-Blackwellised particle filtering to DBNs in general, and the SLAM (simultaneous localization and mapping) problem in particular; a way of extending the structural EM algorithm to DBNs; and a variety of different applications of DBNs. However, perhaps the main value of the thesis is its catholic presentation of the field of sequential data modelling.

Recently, there has been much interest in reverse engineering genetic networks from time series data. In this paper, we show that most of the proposed discrete time models — including the boolean network model [Kau93, SS96], the linear model of D’haeseleer et al. [DWFS99], and the nonlinear model of Weaver et al. [WWS99] — are all special cases of a general class of models called Dynamic Bayesian Networks (DBNs). The advantages of DBNs include the ability to model stochasticity, to incorporate prior knowledge, and to handle hidden variables and missing data in a principled way. This paper provides a review of techniques for learning DBNs. Keywords: Genetic networks, boolean networks, Bayesian networks, neural networks, reverse engineering, machine learning. 1

Motivation: Bayesian networks have been applied to infer genetic regulatory interactions from microarray gene expression data. This inference problem is particularly hard in that interactions between hundreds of genes have to be learned from very small data sets, typically containing only a few dozen time points during a cell cycle. Most previous studies have assessed the inference results on real gene expression data by comparing predicted genetic regulatory interactions with those known from the biological literature. This approach is controversial due to the absence of known gold standards, which renders the estimation of the sensitivity and specificity, that is, the true and (complementary) false detection rate, unreliable and difficult. The objective of the present study is to test the viability of the Bayesian network paradigm in a realistic simulation study. First, gene expression data are simulated from a realistic biological network involving DNAs, mRNAs, inactive protein monomers and active protein dimers. Then, interaction networks are inferred from these data in a reverse engineering approach, using Bayesian networks and Bayesian learning with Markov chain Monte Carlo. Results: The simulation results are presented as receiver operator characteristics curves. This allows estimating the proportion of spurious gene interactions incurred for a specified target proportion of recovered true interactions. The findings demonstrate how the network inference performance varies with the training set size, the degree of inadequacy of prior assumptions, the experimental sampling strategy and the inclusion of further, sequence-based information.

Dynamic Probabilistic Networks (DPNs) are exploited for modelling the temporal relationships among a set of different object temporal events in the scene for a coherent and robust scene-level behaviour interpretation. In particular, we develop a Dynamically Multi-Linked Hidden Markov Model (DML-HMM) to interpret group activities involving multiple objects captured in an outdoor scene. The model is based on the discovery of salient dynamic interlinks among multiple temporal events using DPNs. Object temporal events are detected and labelled using Gaussian Mixture Models with automatic model order selection. A DML-HMM is built using Schwarz’s Bayesian Information Criterion based factorisation resulting in its topology being intrinsically determined by the underlying causality and temporal order among different object events. Our experiments demonstrate that its performance on modelling group activities in a noisy outdoor scene is superior compared to that of a Multi-Observation Hidden Markov Model (MOHMM), a Parallel Hidden Markov Model (PaHMM) and a Coupled

In this work, dynamic Bayesian multinets are introduced where a Markov chain state at time t determines conditional independence patterns between random variables lying within a local time window surrounding t. It is shown how information-theoretic criterion functions can be used to induce sparse, discriminative, and classconditional network structures that yield an optimal approximation to the class posterior probability, and therefore are useful for the classification task. Using a new structure learning heuristic, the resulting models are tested on a medium-vocabulary isolated-word speech recognition task. It is demonstrated that these discriminatively structured dynamic Bayesian multinets, when trained in a maximum likelihood setting using EM, can outperform both HMMs and other dynamic Bayesian networks with a similar number of parameters. 1 Introduction While Markov chains are sometimes a useful model for sequences, such simple independence assumptions can lead...

Graphical models provide a promising paradigm to study both existing and novel techniques for automatic speech recognition. This paper first provides a brief overview of graphical models and their uses as statistical models. It is then shown that the statistical assumptions behind many pattern recognition techniques commonly used as part of a speech recognition system can be described by a graph – this includes Gaussian distributions, mixture models, decision trees, factor analysis, principle component analysis, linear discriminant analysis, and hidden Markov models. Moreover, this paper shows that many advanced models for speech recognition and language processing can also be simply described by a graph, including many at the acoustic-, pronunciation-, and language-modeling levels. A number of speech recognition techniques born directly out of the graphical-models paradigm are also surveyed. Additionally, this paper includes a novel graphical analysis regarding why derivative (or delta) features improve hidden Markov model-based speech recognition by improving structural discriminability. It also includes an example where a graph can be used to represent language model smoothing constraints. As will be seen, the space of models describable by a graph is quite large. A thorough exploration of this space should yield techniques that ultimately will supersede the hidden Markov model.

Supervised classification is one of the most active areas of machine learning research. Most work has focused on classification in static domains, where an instantaneous snapshot of attributes is meaningful. In many domains, attributes are not static; in fact, it is the way they vary temporally that can make classification possible. Examples of such domains include speech recognition, gesture recognition and electrocardiograph classification. While it is possible to use ad hoc, domain-specific techniques for "flattening " the time series to a learner-friendly representation, this fails to take into account both the special problems and special heuristics applicable to temporal data and often results in unreadable concept descriptions. Though traditional time series techniques can sometimes produce accurate classifiers, few can provide comprehensible descriptions. We propose a general architecture for classification and description of multivariate time series. It employs event primitive...

Abstract. We propose a dynamic Bayesian network and nonparametric regression model for constructing a gene network from time series microarray gene expression data. The proposed method can overcome a shortcoming of the Bayesian network model in the sense of the construction of cyclic regulations. The proposed method can analyze the microarray data as continuous data and can capture even nonlinear relations among genes. It can be expected that this model will give a deeper insight into the complicated biological systems. We also derive a new criterion for evaluating an estimated network from Bayes approach. We demonstrate the effectiveness of our method by analyzing Saccharomyces cerevisiae gene expression data. 1

Motivation: Cells continuously reprogram their gene expression network as they move through the cell cycle or sense changes in their environment. In order to understand the regulation of cells, time series expression profiles provide a more complete picture than single time point expression profiles. Few analysis techniques, however, are well suited to modelling such time series data.