| Metabolism encompasses essential processes of living organisms. Reconstruction of detailed metabolic models of several organisms provides the means to analyze functional and organizational aspects of metabolism on a system-wide scale. The presented work investigates how functional requirements of metabolism manifest themselves in topological organization of the metabolic network.; Our analysis begins by studying patterns of co-regulated genes in a metabolic network. Based on mRNA co-expression patterns and distribution of known transcription factor binding sites, we illustrate predominance of local regulation of the metabolic network. We show that strongest co-regulation is observed in specific network topologies of metabolically adjacent enzymes. At higher levels, we demonstrate localized co-regulated regions spanning increasing portions of the metabolic network. The second chapter illustrates that local topological properties of the metabolic network, such as connectivity, correlate with evolutionary and functional characteristics of the metabolic enzymes. Furthermore, we show that local property can be observed in many types of functional and evolutionary association, such as co-occurrence in phylogenetic profiles or clustering of genes on the chromosome.; Based on these observations we develop a method for identifying candidate genes encoding a specific metabolic function. We illustrate that the approach is applicable to many types of associating evidence, and develop efficient ways of combining such information. We demonstrate that the method is able to predict approximately 60% of known enzyme-encoding genes within the top ten candidates for their enzymatic function. The predictions generated by this method are complementary to traditional homology-based identification approaches. |
