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B. Thuringiensis Metabolic Network Reconstruction And Its Analysis

Posted on:2009-10-01Degree:MasterType:Thesis
Country:ChinaCandidate:D W DingFull Text:PDF
GTID:2120360272957362Subject:Computer application technology
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B. thuringiensis is applied and researched worldwide as an insecticidal bacterium nowadays, however current research have focused on traditional experimentation which is supervised by reductionism. To describe, interpret and predict the functional capabilities of B. thuringiensis from a system-oriented perspective, deeply understand the organization of fundamental, and with the purpose of selection of stains, optimization of fermentation process etc., the dissertation reconstructed the metabolic network of B. thuringiensis from its genome, and analyzed its global topological properties, modularity and correlative metabolic pathways from a systems biologic perspective.The basis of structural and functional analysis of metabolic network is its reconstruction, we first obtained all metabolic reactions involved in metabolic network of B. thuringiensis from KEGG and correlative database, and all of the reactions are revised based a KEGG-based database developed by Ma and Zeng and correlative literatures. Then, the metabolic network reconstructed is represented by so-called metabolite graph in which the nodes are metabolites and the links are reactions.Subsequently, we simplified reconstructed network based on its "bow tie", by investigating the giant strong component (GSC) of "bow tie", we found that it contains the most important modules and its hubs are functional significant. Then, we investigated the GSC from the following aspects: 1) average path length, i.e. the steps of conversion between two metabolites, 2) degree distribution, i.e. the probability of a node with degree k, and 3) robustness, which focused on error and attack tolerance. The results have shown that the GSC of B. thuringiensis metabolic network is also a small-world and scale-free network. Furthermore, it is suggested that metabolic networks should have modularity which is similar to social networks, to explore underlying functional capabilities, we used simulated annealing algorithm for decomposition of GSC, and found that these divisions are functional significant. At last, we employed extreme pathways to investigate poly-beta-hydroxybutyrate (PHB) metabolism, the results suggested that there are some novel pathways which will provide a potential mechanism to optimize the accumulation of PHB.
Keywords/Search Tags:metabolic network, modularity, pathway analysis, systems biology, topological structure
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