{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:48:08Z","timestamp":1781977688963,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011381","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012948","name":"Minist\u00e8re de l\u2019Enseignement sup\u00e9rieur, de la Recherche et de l\u2019Innovation","doi-asserted-by":"publisher","award":["2020-2"],"award-info":[{"award-number":["2020-2"]}],"id":[{"id":"10.13039\/100012948","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MetaboHUB","award":["Grant 11-INBS-0010"],"award-info":[{"award-number":["Grant 11-INBS-0010"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-INBS-0010"],"award-info":[{"award-number":["ANR-INBS-0010"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-19-CE45-0021"],"award-info":[{"award-number":["ANR-19-CE45-0021"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG: 431572533"],"award-info":[{"award-number":["DFG: 431572533"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Metabolic profiling (metabolomics) aims at measuring small molecules (metabolites) in complex samples like blood or urine for human health studies. While biomarker-based assessment often relies on a single molecule, metabolic profiling combines several metabolites to create a more complex and more specific fingerprint of the disease. However, in contrast to genomics, there is no unique metabolomics setup able to measure the entire metabolome. This challenge leads to tedious and resource consuming preliminary studies to be able to design the right metabolomics experiment. In that context, computer assisted metabolic profiling can be of strong added value to design metabolomics studies more quickly and efficiently. We propose a constraint-based modelling approach which predicts\n                    <jats:italic>in silico<\/jats:italic>\n                    profiles of metabolites that are more likely to be differentially abundant under a given metabolic perturbation (e.g. due to a genetic disease), using flux simulation. In genome-scale metabolic networks, the fluxes of exchange reactions, also known as the flow of metabolites through their external transport reactions, can be simulated and compared between control and disease conditions in order to calculate changes in metabolite import and export. These import\/export flux differences would be expected to induce changes in circulating biofluid levels of those metabolites, which can then be interpreted as potential biomarkers or metabolites of interest. In this study, we present SAMBA (SAMpling Biomarker Analysis), an approach which simulates fluxes in exchange reactions following a metabolic perturbation using random sampling, compares the simulated flux distributions between the baseline and modulated conditions, and ranks predicted differentially exchanged metabolites as potential biomarkers for the perturbation. We show that there is a good fit between simulated metabolic exchange profiles and experimental differential metabolites detected in plasma, such as patient data from the disease database OMIM, and metabolic trait-SNP associations found in mGWAS studies. These biomarker recommendations can provide insight into the underlying mechanism or metabolic pathway perturbation lying behind observed metabolite differential abundances, and suggest new metabolites as potential avenues for further experimental analyses.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1011381","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T13:33:30Z","timestamp":1708608810000},"page":"e1011381","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genome scale metabolic network modelling for metabolic profile 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Frainay","year":"2018","journal-title":"Metabolites"},{"issue":"3","key":"pcbi.1011381.ref004","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.trac.2008.01.008","article-title":"LC-MS-based methodology for global metabolite profiling in metabonomics\/metabolomics","volume":"27","author":"G Theodoridis","year":"2008","journal-title":"TrAC Trends in Analytical Chemistry"},{"issue":"2","key":"pcbi.1011381.ref005","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00216-006-0687-8","article-title":"Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics","volume":"387","author":"Z Pan","year":"2007","journal-title":"Analytical and Bioanalytical Chemistry"},{"issue":"3","key":"pcbi.1011381.ref006","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"LW Sumner","year":"2007","journal-title":"Metabolomics: Official journal of the Metabolomic Society"},{"issue":"3","key":"pcbi.1011381.ref007","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance analysis?","volume":"28","author":"JD Orth","year":"2010","journal-title":"Nature Biotechnology"},{"issue":"1","key":"pcbi.1011381.ref008","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nprot.2009.203","article-title":"A protocol for generating a high-quality genome-scale metabolic reconstruction","volume":"5","author":"I Thiele","year":"2010","journal-title":"Nature Protocols"},{"key":"pcbi.1011381.ref009","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1752-0509-4-140","article-title":"A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1","volume":"4","author":"MI Sigurdsson","year":"2010","journal-title":"BMC systems 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Thiele","year":"2020","journal-title":"Molecular Systems Biology"},{"key":"pcbi.1011381.ref013","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/msb.2009.22","article-title":"Predicting metabolic biomarkers of human inborn errors of metabolism","volume":"5","author":"T Shlomi","year":"2009","journal-title":"Molecular Systems Biology"},{"issue":"5","key":"pcbi.1011381.ref014","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nbt.2488","article-title":"A community-driven global reconstruction of human metabolism","volume":"31","author":"I Thiele","year":"2013","journal-title":"Nature Biotechnology"},{"issue":"4","key":"pcbi.1011381.ref015","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ymben.2003.09.002","article-title":"The effects of alternate optimal solutions in constraint-based genome-scale metabolic models","volume":"5","author":"R Mahadevan","year":"2003","journal-title":"Metabolic Engineering"},{"key":"pcbi.1011381.ref016","doi-asserted-by":"crossref","unstructured":"Smith RL. The hit-and-run sampler: a globally reaching Markov chain sampler for generating arbitrary multivariate distributions. In: Proceedings of the 28th conference on Winter simulation. WSC\u201996. USA: IEEE Computer Society; 1996. p. 260\u2013264. Available from: https:\/\/dl.acm.org\/doi\/10.1145\/256562.256619.","DOI":"10.1145\/256562.256619"},{"issue":"4","key":"pcbi.1011381.ref017","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1529\/biophysj.104.043000","article-title":"Uniform Sampling of Steady-State Flux Spaces: Means to Design Experiments and to Interpret Enzymopathies","volume":"87","author":"ND Price","year":"2004","journal-title":"Biophysical Journal"},{"issue":"7","key":"pcbi.1011381.ref018","doi-asserted-by":"crossref","first-page":"e0235393","DOI":"10.1371\/journal.pone.0235393","article-title":"A comparison of Monte Carlo sampling methods for metabolic network models","volume":"15","author":"S Fallahi","year":"2020","journal-title":"PLOS ONE"},{"issue":"1","key":"pcbi.1011381.ref019","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1752-0509-3-37","article-title":"Connecting extracellular metabolomic measurements to intracellular flux states in yeast","volume":"3","author":"ML Mo","year":"2009","journal-title":"BMC Systems Biology"},{"issue":"6804","key":"pcbi.1011381.ref020","first-page":"182","article-title":"Xanthinuria, an inborn error (or deviation) of metabolism","volume":"266","author":"CE Dent","year":"1954","journal-title":"Lancet (London, England)"},{"issue":"2","key":"pcbi.1011381.ref021","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s00467-006-0267-3","article-title":"Xanthinuria type I: a rare cause of urolithiasis","volume":"22","author":"N Arikyants","year":"2007","journal-title":"Pediatric Nephrology"},{"issue":"Database Issue","key":"pcbi.1011381.ref022","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"A Hamosh","year":"2005","journal-title":"Nucleic Acids Research"},{"issue":"10","key":"pcbi.1011381.ref023","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1039\/c2mb25075f","article-title":"A compendium of inborn errors of metabolism mapped onto the human metabolic network","volume":"8","author":"S Sahoo","year":"2012","journal-title":"Molecular BioSystems"},{"issue":"7362","key":"pcbi.1011381.ref024","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature10354","article-title":"Human metabolic individuality in biomedical and pharmaceutical research","volume":"477","author":"K Suhre","year":"2011","journal-title":"Nature"},{"issue":"2","key":"pcbi.1011381.ref025","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/ng.507","article-title":"A genome-wide perspective of genetic variation in human metabolism","volume":"42","author":"T Illig","year":"2010","journal-title":"Nature 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Moreno","year":"2015","journal-title":"BMC Bioinformatics"},{"issue":"2","key":"pcbi.1011381.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002490","article-title":"Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations","volume":"8","author":"A Demirkan","year":"2012","journal-title":"PLoS Genetics"},{"issue":"1","key":"pcbi.1011381.ref033","doi-asserted-by":"crossref","first-page":"E28","DOI":"10.1152\/ajpendo.90897.2008","article-title":"Biochemical and physiological function of stearoyl-CoA desaturase","volume":"297","author":"CM Paton","year":"2009","journal-title":"American Journal of Physiology\u2014Endocrinology and Metabolism"},{"issue":"2","key":"pcbi.1011381.ref034","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.3390\/molecules20022425","article-title":"A Review of Odd-Chain Fatty Acid Metabolism and the Role of Pentadecanoic Acid (C15:0) and Heptadecanoic Acid (C17:0) in Health and Disease","volume":"20","author":"B Jenkins","year":"2015","journal-title":"Molecules"},{"issue":"1","key":"pcbi.1011381.ref035","doi-asserted-by":"crossref","first-page":"14567","DOI":"10.1038\/s41598-017-15231-w","article-title":"Chemical Similarity Enrichment Analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets","volume":"7","author":"DK Barupal","year":"2017","journal-title":"Scientific Reports"},{"issue":"9","key":"pcbi.1011381.ref036","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/S0022-2275(20)33401-5","article-title":"Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol","volume":"40","author":"JM Ntambi","year":"1999","journal-title":"Journal of Lipid Research"},{"issue":"3","key":"pcbi.1011381.ref037","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.3390\/ijms23031014","article-title":"The Role of Vitamin A in Retinal Diseases","volume":"23","author":"J Sajovic","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"issue":"2","key":"pcbi.1011381.ref038","first-page":"274","article-title":"MetaboRank: network-based recommendation system to interpret and enrich metabolomics results","volume":"35","author":"C Frainay","year":"2019","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"3","key":"pcbi.1011381.ref039","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification","volume":"78","author":"CA Smith","year":"2006","journal-title":"Analytical Chemistry"},{"issue":"11","key":"pcbi.1011381.ref040","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1093\/bioinformatics\/btx052","article-title":"CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models","volume":"33","author":"HS 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DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks; 2020. 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