{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T15:33:50Z","timestamp":1774366430598,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1007424","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011735","name":"Bioenergy Technologies Office","doi-asserted-by":"publisher","award":["DE-AC36-08GO28308"],"award-info":[{"award-number":["DE-AC36-08GO28308"]}],"id":[{"id":"10.13039\/100011735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007424","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T13:35:10Z","timestamp":1572874510000},"page":"e1007424","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Bayesian inference of metabolic kinetics from genome-scale multiomics data"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7928-3722","authenticated-orcid":true,"given":"Peter C.","family":"St. John","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Strutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda J.","family":"Broadbelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-0687","authenticated-orcid":true,"given":"Keith E. J.","family":"Tyo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7624-8000","authenticated-orcid":true,"given":"Yannick J.","family":"Bomble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"pcbi.1007424.ref001","doi-asserted-by":"crossref","DOI":"10.2172\/1107470","volume-title":"Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbons: Dilute-Acid and Enzymatic Deconstruction of Biomassto Sugars and Biological Conversion of Sugars to Hydrocarbons","author":"R Davis","year":"2013"},{"issue":"6","key":"pcbi.1007424.ref002","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.cell.2016.02.004","article-title":"Engineering Cellular Metabolism","volume":"164","author":"J Nielsen","year":"2016","journal-title":"Cell"},{"issue":"2","key":"pcbi.1007424.ref003","first-page":"287","article-title":"Integrating multiple \u2018omics\u2019 analysis for microbial biology: application and methodologies","volume":"156","author":"W Zhang","year":"2009","journal-title":"Microbiology+"},{"issue":"6311","key":"pcbi.1007424.ref004","doi-asserted-by":"crossref","first-page":"aaf2786","DOI":"10.1126\/science.aaf2786","article-title":"Systems-level analysis of mechanisms regulating yeast metabolic flux","volume":"354","author":"SR Hackett","year":"2016","journal-title":"Science"},{"key":"pcbi.1007424.ref005","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.copbio.2018.01.027","article-title":"Advances in analytical tools for high throughput strain engineering","volume":"54","author":"E Marcellin","year":"2018","journal-title":"Current Opinion in Biotechnology"},{"key":"pcbi.1007424.ref006","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2019.00597","article-title":"Approaches to Computational Strain Design in the Multiomics Era","volume":"10","author":"PC St John","year":"2019","journal-title":"Frontiers in Microbiology"},{"issue":"3","key":"pcbi.1007424.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":"Nat Biotechnol"},{"issue":"5","key":"pcbi.1007424.ref008","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1529\/biophysj.106.093138","article-title":"Thermodynamics-Based Metabolic Flux Analysis","volume":"92","author":"CS Henry","year":"2007","journal-title":"Biophys J"},{"issue":"8","key":"pcbi.1007424.ref009","doi-asserted-by":"crossref","first-page":"935","DOI":"10.15252\/msb.20167411","article-title":"Improving the phenotype predictions of a yeast genome-scale metabolicmodel by incorporating enzymatic constraints","volume":"13","author":"BJ S\u00e1nchez","year":"2017","journal-title":"Molecular Systems Biology"},{"key":"pcbi.1007424.ref010","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.copbio.2014.02.011","article-title":"Recent advances in the reconstruction of metabolic models andintegration of omics data","volume":"29","author":"R Saha","year":"2014","journal-title":"Curr Opin Biotech"},{"key":"pcbi.1007424.ref011","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.copbio.2015.08.011","article-title":"Improving prediction fidelity of cellular metabolism with kinetic descriptions","volume":"36","author":"A Chowdhury","year":"2015","journal-title":"Curr Opin Biotech"},{"issue":"6","key":"pcbi.1007424.ref012","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.cels.2017.11.013","article-title":"Metabolic Models of Protein Allocation Call for the Kinetome","volume":"5","author":"A Nilsson","year":"2017","journal-title":"Cell Systems"},{"issue":"12","key":"pcbi.1007424.ref013","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1529\/biophysj.108.135442","article-title":"Ensemble Modeling of Metabolic Networks","volume":"95","author":"LM Tran","year":"2008","journal-title":"Biophys J"},{"issue":"1","key":"pcbi.1007424.ref014","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1073\/pnas.1716056115","article-title":"Dissecting the genetic and metabolic mechanisms of adaptation to the knockout of a major metabolic enzyme in Escherichia coli","volume":"115","author":"CP Long","year":"2017","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1007424.ref015","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ymben.2014.05.014","article-title":"A kinetic model of Escherichia coli core metabolism satisfying multiple sets of mutant flux data","volume":"25","author":"A Khodayari","year":"2014","journal-title":"Metab Eng"},{"issue":"8","key":"pcbi.1007424.ref016","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.biotechadv.2017.09.005","article-title":"Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks","volume":"35","author":"PA Saa","year":"2017","journal-title":"Biotechnology Advances"},{"issue":"8","key":"pcbi.1007424.ref017","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.tibtech.2010.05.003","article-title":"Production of biofuels and biochemicals: in need of an ORACLE","volume":"28","author":"L Miskovic","year":"2010","journal-title":"Trends Biotechnol"},{"issue":"6","key":"pcbi.1007424.ref018","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1529\/biophysj.104.048090","article-title":"Metabolic Control Analysis under Uncertainty: Framework Developmentand Case Studies","volume":"87","author":"L Wang","year":"2004","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1007424.ref019","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ymben.2005.11.003","article-title":"Metabolic engineering under uncertainty. I: Framework development","volume":"8","author":"L Wang","year":"2006","journal-title":"Metabolic Engineering"},{"issue":"2","key":"pcbi.1007424.ref020","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ymben.2005.11.002","article-title":"Metabolic engineering under uncertainty\u2014II: Analysis of yeastmetabolism","volume":"8","author":"L Wang","year":"2006","journal-title":"Metabolic Engineering"},{"issue":"1","key":"pcbi.1007424.ref021","article-title":"Construction of feasible and accurate kinetic models of metabolism: A Bayesian approach","volume":"6","author":"PA Saa","year":"2016","journal-title":"Scientific Reports"},{"issue":"5","key":"pcbi.1007424.ref022","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.bpj.2017.07.018","article-title":"Acceleration Strategies to Enhance Metabolic Ensemble Modeling Performance","volume":"113","author":"JL Greene","year":"2017","journal-title":"Biophysical Journal"},{"issue":"9","key":"pcbi.1007424.ref023","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/biot.201200270","article-title":"Optimization-driven identification of genetic perturbations accelerates the convergence of model parameters in ensemble modeling of metabolic networks","volume":"8","author":"AR Zomorrodi","year":"2013","journal-title":"Biotechnology Journal"},{"issue":"3","key":"pcbi.1007424.ref024","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S1096-7176(03)00025-9","article-title":"Dynamic simulation and metabolic re-design of a branched pathway using linlog kinetics","volume":"5","author":"D Visser","year":"2003","journal-title":"Metab Eng"},{"issue":"4","key":"pcbi.1007424.ref025","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ymben.2004.07.001","article-title":"Optimal re-design of primary metabolism in Escherichiacoli using linlog kinetics","volume":"6","author":"D Visser","year":"2004","journal-title":"Metab Eng"},{"issue":"15","key":"pcbi.1007424.ref026","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1016\/S0009-2509(97)00076-6","article-title":"A general formalism for Metabolic Control Analysis","volume":"52","author":"M Ehlde","year":"1997","journal-title":"Chem Eng Sci"},{"issue":"2","key":"pcbi.1007424.ref027","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1006\/mben.2001.0216","article-title":"The Mathematics of Metabolic Control Analysis Revisited","volume":"4","author":"D Visser","year":"2002","journal-title":"Metab Eng"},{"issue":"1","key":"pcbi.1007424.ref028","first-page":"1593","article-title":"The No-U-turn sampler: adaptively setting path lengths in Hamiltonian Monte Carlo","volume":"15","author":"MD Hoffman","year":"2014","journal-title":"Journal of Machine Learning Research"},{"key":"pcbi.1007424.ref029","first-page":"14:1","article-title":"Automatic Differentiation Variational Inference","volume":"18","author":"A Kucukelbir","year":"2017","journal-title":"Journal of Machine Learning Research"},{"issue":"16","key":"pcbi.1007424.ref030","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1111\/j.0014-2956.2004.04269.x","article-title":"A new framework for the estimation of control parameters in metabolicpathways using lin-log kinetics","volume":"271","author":"L Wu","year":"2004","journal-title":"Eur J Biochem"},{"issue":"1-2","key":"pcbi.1007424.ref031","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1432-1033.1995.tb20376.x","article-title":"Determining Elasticities from Multiple Measurements of Flux Rates and Metabolite Concentrations. Application of the Multiple Modulation Method to a Reconstituted Pathway","volume":"227","author":"C Giersch","year":"1995","journal-title":"Eur J Biochem"},{"key":"pcbi.1007424.ref032","unstructured":"Blundell C, Cornebise J, Kavukcuoglu K, Wierstra D. Weight Uncertainty in Neural Networks. In: Proceedings of the 32Nd International Conference on International Conference on Machine Learning\u2014Volume 37. ICML\u201915; 2015. p. 1613\u20131622."},{"issue":"3-4","key":"pcbi.1007424.ref033","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0025-5564(70)90132-X","article-title":"On structural identifiability","volume":"7","author":"R Bellman","year":"1970","journal-title":"Mathematical Biosciences"},{"issue":"4-5","key":"pcbi.1007424.ref034","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ymben.2009.04.002","article-title":"Ensemble modeling for strain development of l-lysine-producing Escherichia coli","volume":"11","author":"CA Contador","year":"2009","journal-title":"Metab Eng"},{"key":"pcbi.1007424.ref035","unstructured":"Kojima H, Ogawa Y, Kawamura K, Sano K. Method of producing L-lysine by fermentation; 1993. US Patent US6040160A."},{"issue":"3","key":"pcbi.1007424.ref036","doi-asserted-by":"crossref","first-page":"e1002415","DOI":"10.1371\/journal.pcbi.1002415","article-title":"System-Level Insights into Yeast Metabolism by Thermodynamic Analysis of Elementary Flux Modes","volume":"8","author":"SJ Jol","year":"2012","journal-title":"PLoS Computational Biology"},{"key":"pcbi.1007424.ref037","unstructured":"Rezende D, Mohamed S. Variational Inference with Normalizing Flows. In: Bach F, Blei D, editors. Proceedings of the 32nd International Conference on Machine Learning. vol. 37 of Proceedings of Machine Learning Research. Lille, France: PMLR; 2015. p. 1530\u20131538."},{"key":"pcbi.1007424.ref038","unstructured":"Knollm\u00fcller J, En\u00dflin TA. Metric Gaussian Variational Inference. arXiv. 2019; p. arXiv:1901.11033."},{"issue":"1","key":"pcbi.1007424.ref039","first-page":"1303","article-title":"Stochastic variational inference","volume":"14","author":"MD Hoffman","year":"2013","journal-title":"The Journal of Machine Learning Research"},{"key":"pcbi.1007424.ref040","first-page":"543","article-title":"Firefly Monte Carlo: exact MCMC with subsets of data","author":"D Maclaurin","year":"2014","journal-title":"Proceedings of the Thirtieth Conference on Uncertainty in Artificial Intelligence"},{"issue":"4","key":"pcbi.1007424.ref041","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1103\/PhysRev.37.405","article-title":"Reciprocal Relations in Irreversible Processes. I","volume":"37","author":"L Onsager","year":"1931","journal-title":"Physical Review"},{"issue":"6","key":"pcbi.1007424.ref042","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0006-3495(73)86004-7","article-title":"The Thermodynamic Description of Enzyme-Catalyzed Reactions","volume":"13","author":"H Rottenberg","year":"1973","journal-title":"Biophysical Journal"},{"issue":"2","key":"pcbi.1007424.ref043","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/0005-2728(80)90179-6","article-title":"Linear relation between rate and thermodynamic force inenzyme-catalyzed reactions","volume":"591","author":"R van der Meer","year":"1980","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Bioenergetics"},{"issue":"1","key":"pcbi.1007424.ref044","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ymben.2008.07.004","article-title":"Model reduction and a priori kinetic parameteridentifiability analysis using metabolome time series for metabolic reaction networks with linlog kinetics","volume":"11","author":"IE Nikerel","year":"2009","journal-title":"Metabolic Engineering"},{"issue":"1","key":"pcbi.1007424.ref045","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1186\/1471-2105-7-540","article-title":"A method for estimation of elasticities in metabolic networks using steady state and dynamic metabolomics data and linlog kinetics","volume":"7","author":"IE Nikerel","year":"2006","journal-title":"BMC Bioinformatics"},{"issue":"2","key":"pcbi.1007424.ref046","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ymben.2004.12.002","article-title":"Determination of elasticities, concentration and flux control coefficients from transient metabolite data using linlog kinetics","volume":"7","author":"MTAP Kresnowati","year":"2005","journal-title":"Metabolic Engineering"},{"issue":"4","key":"pcbi.1007424.ref047","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ymben.2004.07.002","article-title":"Metabolic flux control analysis of branch points: an improved approach to obtain flux control coefficients from large perturbation data","volume":"6","author":"JJ Heijnen","year":"2004","journal-title":"Metabolic Engineering"},{"issue":"9","key":"pcbi.1007424.ref048","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1021\/acssynbio.6b00377","article-title":"In Vitro Metabolic Engineering of Amorpha-4,11-diene Biosynthesis at Enhanced Rate and Specific Yield of Production","volume":"6","author":"X Chen","year":"2017","journal-title":"ACS Synthetic Biology"},{"issue":"5824","key":"pcbi.1007424.ref049","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1132067","article-title":"Multiple High-Throughput Analyses Monitor the Response of E. coli to Perturbations","volume":"316","author":"N Ishii","year":"2007","journal-title":"Science"},{"key":"pcbi.1007424.ref050","volume-title":"The Matrix Cookbook","author":"KB Petersen","year":"2012"},{"issue":"21","key":"pcbi.1007424.ref051","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1111\/j.1742-4658.2007.06076.x","article-title":"Something from nothing\u2014bridging the gap between constraint-basedand kinetic modelling","volume":"274","author":"K Smallbone","year":"2007","journal-title":"FEBS Journal"},{"issue":"5","key":"pcbi.1007424.ref052","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/bies.200900167","article-title":"The biological significance of substrate inhibition: A mechanism with diverse functions","volume":"32","author":"MC Reed","year":"2010","journal-title":"BioEssays"},{"issue":"1","key":"pcbi.1007424.ref053","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1091\/mbc.e09-07-0597","article-title":"Growth-limiting Intracellular Metabolites in Yeast Growing under Diverse Nutrient Limitations","volume":"21","author":"VM Boer","year":"2010","journal-title":"Molecular Biology of the Cell"},{"key":"pcbi.1007424.ref054","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.7717\/peerj-cs.55","article-title":"Probabilistic programming in Python using PyMC3","volume":"2","author":"J Salvatier","year":"2016","journal-title":"PeerJ Computer Science"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1007424","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007424","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T13:59:34Z","timestamp":1573739974000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007424"}},"subtitle":[],"editor":[{"given":"Costas D.","family":"Maranas","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,11,4]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007424","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/450163","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.736855200.793593529","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,4]]}}}