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Previous studies in this area mainly focused on Pearson correlation coefficients, which however are generally incapable of distinguishing between direct and indirect metabolic interactions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In our new approach we propose the application of a Gaussian graphical model (GGM), an undirected probabilistic graphical model estimating the conditional dependence between variables. GGMs are based on partial correlation coefficients, that is pairwise Pearson correlation coefficients conditioned against the correlation with all other metabolites. We first demonstrate the general validity of the method and its advantages over regular correlation networks with computer-simulated reaction systems. Then we estimate a GGM on data from a large human population cohort, covering 1020 fasting blood serum samples with 151 quantified metabolites. The GGM is much sparser than the correlation network, shows a modular structure with respect to metabolite classes, and is stable to the choice of samples in the data set. On the example of human fatty acid metabolism, we demonstrate for the first time that high partial correlation coefficients generally correspond to known metabolic reactions. This feature is evaluated both manually by investigating specific pairs of high-scoring metabolites, and then systematically on a literature-curated model of fatty acid synthesis and degradation. Our method detects many known reactions along with possibly novel pathway interactions, representing candidates for further experimental examination.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In summary, we demonstrate strong signatures of intracellular pathways in blood serum data, and provide a valuable tool for the unbiased reconstruction of metabolic reactions from large-scale metabolomics data sets.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-21","type":"journal-article","created":{"date-parts":[[2011,2,8]],"date-time":"2011-02-08T14:55:38Z","timestamp":1297176938000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":277,"title":["Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data"],"prefix":"10.1186","volume":"5","author":[{"given":"Jan","family":"Krumsiek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Suhre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Illig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian J","family":"Theis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,1,31]]},"reference":[{"issue":"19","key":"608_CR1","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1128\/JB.180.19.5109-5116.1998","volume":"180","author":"H Tweeddale","year":"1998","unstructured":"Tweeddale H, Notley-McRobb L, Ferenci T: Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool (\"metabolome\") analysis. 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