CIS-REGULATORY MODULE ANALYSIS: INFERRING REGULATORY NETWORKS AND UNDERLYING MECHANISMS BY

ii A major challenge in understanding metazoan genomes is to find and annotate the regions that control the precise spatial and temporal expression of the genes. Cis-regulatory modules (CRMs/enhancers), main players of this regulatory process, are typically short (<1kb) sequences that are embedded in non-coding regions of the genome. They harbor cis-elements (binding sites/motifs) for one or more related transcription factors (TFs) and mediate a discrete aspect of the expression pattern of their nearby gene. Although decades of research in biology have provided scientists with hundreds of such sequences, we are far from completing the search and understanding the underlying mechanisms of these regulatory regions. The goal of this thesis is to utilize computational and statistical methods to guide the search for novel CRMs, reveal the mechanisms of this regulatory action, and elucidate specific biological networks using the developed methodology. The first part of my thesis develops several statistical methods to find nove