Computational methods for analysis and modeling of time -course gene expression data

Genes encode proteins, some of which in turn regulate other genes. Such interactions make up gene regulatory relationships or (dynamic) gene regulatory networks. With advances in the measurement technology for gene expression and in genome sequencing, it has become possible to measure the expression level of thousands of genes simultaneously in a cell at a series of time points over a specific biological process. Such time-course gene expression data may provide a snapshot of most (if not all) of the interesting genes and may lead to a better understanding gene regulatory relationships and networks. However, inferring either gene regulatory relationships or networks puts a high demand on powerful computational methods that are capable of sufficiently mining the large quantities of time-course gene expression data, while reducing the complexity of the data to make them comprehensible. This dissertation presents several computational methods for inferring gene regulatory relationships and gene regulatory networks from time-course gene expression. These methods are the result of the author's doctoral study.;Cluster analysis plays an important role for inferring gene regulatory relationships, for example, uncovering new regulons (sets of co-regulated genes) and their putative cis-regulatory elements. Two dynamic model-based clustering methods, namely the Markov chain model (MCM)-based clustering and the autoregressive model (ARM)-based clustering, are developed for time-course gene expression data. However, gene regulatory relationships based on cluster analysis are static and thus do not describe the dynamic evolution of gene expression over an observation period. The gene regulatory network is believed to be a time-varying system. Consequently, a state-space model for dynamic gene regulatory networks from time-course gene expression data is developed. To account for the complex time-delayed relationships in gene regulatory networks, the state space model is extended to be the one with time delays. Finally, a method based on genetic algorithms is developed to infer the time-delayed relationships in gene regulatory networks. Validations of all these developed methods are based on the experimental data available from well-cited public databases.