Combining heterogeneous sources of data for the reverse-engineering of gene regulatory networks

Abstract

Gene Regulatory Networks (GRNs) represent how genes interact in various cellular processes by describing how the expression level, or activity, of genes can affect the expression of the other genes. Reverse-engineering GRN models can help biologists understand and gain insight into genetic conditions and diseases. Recently, the increasingly widespread use of DNA microarrays, a high-throughput technology that allows the expression of thousands of genes to be measured simultaneously in biological experiments, has led to many datasets of gene expression measurements becoming publicly available and a subsequent explosion of research in the reverse-engineering of GRN models. However, microarray technology has a number of limitations as a data source for the modelling of GRNs, due to concerns over its reliability and the reproducibility of experimental results. The underlying theme of the research presented in this thesis is the incorporation of multiple sources and different types of data into techniques for reverse-engineering or learning GRNs from data. By drawing on many data sources, the resulting network models should be more robust, accurate and reliable than models that have been learnt using a single data source. This is achieved by focusing on two main strands of research. First, the thesis presents some of the earliest work in the incorporation of prior knowledge that has been generated from a large body of scientific papers, for Bayesian network based GRN models. Second, novel methods for the use of multiple microarray datasets to produce Bayesian network based GRN models are introduced. Empirical evaluations are used to show that the incorporation of literature-based prior knowledge and combining multiple microarray datasets can provide an improvement, when compared to the use of a single microarray dataset, for the reverse-engineering of Bayesian network based GRN models.