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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