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Based on a recently proposed metabolite-centric approach, we here describe a set of methods that enable the analysis and interpretation of flux distributions in an integrated metabolite-centric view. We demonstrate how this framework can be used for the refinement of genome-scale metabolic models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We applied the metabolite-centric view developed here to the most recent metabolic reconstruction of <jats:italic>Escherichia coli<\/jats:italic>. By compiling the balance sheets of a small number of currency metabolites, we were able to fully characterise the energy metabolism as predicted by the model and to identify a possibility for model refinement in NADPH metabolism. Selected branch points were examined in detail in order to demonstrate how a metabolite-centric view allows identifying functional roles of metabolites. Fructose 6-phosphate aldolase and the sedoheptulose bisphosphate bypass were identified as enzymatic reactions that can carry high fluxes in the model but are unlikely to exhibit significant activity <jats:italic>in vivo<\/jats:italic>. Performing a metabolite essentiality analysis, unconstrained import and export of iron ions could be identified as potentially problematic for the quality of model predictions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The system-wide analysis of split ratios and branch points allows a much deeper insight into the metabolic network than reaction-centric analyses. Extending an earlier metabolite-centric approach, the methods introduced here establish an integrated metabolite-centric framework for the interpretation of flux distributions in genome-scale metabolic networks that can complement the classical reaction-centric framework. Analysing fluxes and their metabolic context simultaneously opens the door to systems biological interpretations that are not apparent from isolated reaction fluxes. Particularly powerful demonstrations of this are the analyses of the complete metabolic contexts of energy metabolism and the folate-dependent one-carbon pool presented in this work. Finally, a metabolite-centric view on flux distributions can guide the refinement of metabolic reconstructions for specific growth scenarios.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-7-33","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T16:14:15Z","timestamp":1365783255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A metabolite-centric view on flux distributions in genome-scale metabolic models"],"prefix":"10.1186","volume":"7","author":[{"given":"S Alexander","family":"Riemer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Rex","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Schomburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,4,12]]},"reference":[{"key":"1080_CR1","doi-asserted-by":"publisher","first-page":"17410","DOI":"10.1074\/jbc.274.25.17410","volume":"274","author":"JS Edwards","year":"1999","unstructured":"Edwards JS: Systems properties of the haemophilus influenzae Rd metabolic genotype. 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