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Exploiting the Pathway Structure of Metabolism to Reveal High-Order Epistasis

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dc.contributor.author Imielinski, Marcin en_US
dc.contributor.author Belta, Calin en_US
dc.date.accessioned 2012-01-11T21:09:34Z
dc.date.available 2012-01-11T21:09:34Z
dc.date.copyright 2008 en_US
dc.date.issued 2008-4-30 en_US
dc.identifier.citation Imielinski, Marcin, Calin Belta. "Exploiting the pathway structure of metabolism to reveal high-order epistasis" BMC Systems Biology 2:40. (2008) en_US
dc.identifier.issn 1752-0509 en_US
dc.identifier.uri http://hdl.handle.net/2144/3197
dc.description.abstract BACKGROUND. Biological robustness results from redundant pathways that achieve an essential objective, e.g. the production of biomass. As a consequence, the biological roles of many genes can only be revealed through multiple knockouts that identify a set of genes as essential for a given function. The identification of such "epistatic" essential relationships between network components is critical for the understanding and eventual manipulation of robust systems-level phenotypes. RESULTS. We introduce and apply a network-based approach for genome-scale metabolic knockout design. We apply this method to uncover over 11,000 minimal knockouts for biomass production in an in silico genome-scale model of E. coli. A large majority of these "essential sets" contain 5 or more reactions, and thus represent complex epistatic relationships between components of the E. coli metabolic network. CONCLUSION. The complex minimal biomass knockouts discovered with our approach illuminate robust essential systems-level roles for reactions in the E. coli metabolic network. Unlike previous approaches, our method yields results regarding high-order epistatic relationships and is applicable at the genome-scale. en_US
dc.description.sponsorship National Institutes of Health National Institute of General Medical Sciences (NIH 5T32GM007 170-32) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2008 Imielinski and Belta; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Exploiting the Pathway Structure of Metabolism to Reveal High-Order Epistasis en_US
dc.type article en_US
dc.identifier.doi 10.1186/1752-0509-2-40 en_US
dc.identifier.pubmedid 18447928 en_US
dc.identifier.pmcid 2390508 en_US


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Copyright 2008 Imielinski and Belta; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as Copyright 2008 Imielinski and Belta; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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