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Home | DTI | 2006–07 funded proposals | Friedrich Srienc, Daniel Boley, Arkady Khodursky

Initiatives in Digital Technology: 2006–07 Funded Proposals

Friedrich Srienc, Daniel Boley, Arkady Khodursky

Computation, Organization and Analysis of Metabolic Pathway Data in the Context of Global Transcription Profiles

A metabolic network can be decomposed into a set of unique Elementary Modes. Each Elementary Mode represents a minimal set of enzymes that can operate at steady state with all irreversible reactions used in the appropriate direction. Knowledge of all elementary modes is of significant value as it provides a rigorous basis for rationally designing cells with precisely defined metabolic capabilities. Several different algorithms have been developed to identify the complete set of Elementary Modes inherent in a metabolic network. But all methods are restricted to relatively simple networks that contain only a limited number of elementary modes. Our ongoing work based on these algorithms has recently shown that even for a simple bacterium such as Escherichia coli, described with a simplified metabolic network, the number of elementary modes can exceed 105. It is clear that faster, more efficient algorithms to solve this problem need to be designed and implemented, particularly if the complexity of the metabolic network is increased. Furthermore, the interpretation of the multitude of elementary modes becomes biologically even more meaningful if the metabolic pathways defined in elementary modes can be related to expression data obtained in microarray experiments. To support such effort the data has to be organized in efficient databases that enable the analysis, identification and visualization of relationships that connect the two levels of biological complexity. Success depends on the development and application of scalable algorithms to compute and analyze ever larger metabolic networks. We propose to address this problem with a joint effort between experts in metabolic engineering, computer science and global expression profiling. While this proposal is to initiate such effort and is mainly directed towards the development of algorithms for rapid and efficient computation of elementary modes, it is anticipated that the effort can be expanded as soon as the initial task of elementary mode computation is accomplished. A solution to this problem would be of significant value for biotechnology.