{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T10:55:29Z","timestamp":1759056929031},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T00:00:00Z","timestamp":1358380800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002859","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T16:46:51Z","timestamp":1358441211000},"page":"e1002859","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["ADEMA: An Algorithm to Determine Expected Metabolite Level Alterations Using Mutual Information"],"prefix":"10.1371","volume":"9","author":[{"given":"A. Ercument","family":"Cicek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Bederman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell L.","family":"Drumm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gultekin","family":"Ozsoyoglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2013,1,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1021\/pr9008783","article-title":"Multivariate modeling and prediction of breast cancer prognostic factors using MR metabolomics","volume":"9","author":"GF Giske\u00f8deg\u00e5rd","year":"2010","journal-title":"J Proteome Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.3748\/wjg.v16.i46.5874","article-title":"Metabolomics of gastric cancer metastasis detected by gas chromatography and mass spectrometry","volume":"16","author":"JL Chen","year":"2010","journal-title":"World J Gastroenterol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrc1390","article-title":"Metabolic profiles of cancer cells","volume":"4","author":"JL Griffin","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s00216-009-3317-4","article-title":"Metabolomic investigation of gastric cancer tissue using gas chromatography\/mass spectrometry","volume":"396","author":"H Wu","year":"2010","journal-title":"Anal Bioanal Chem"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"6837","DOI":"10.1016\/j.febslet.2006.11.043","article-title":"Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC\/MS and PLS-LDA","volume":"580","author":"L Yi","year":"2006","journal-title":"FEBS Lett"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"30516","DOI":"10.1074\/jbc.M110.140806","article-title":"Metabolomic profiling beveals biochemical pathways and biomarkers associated with pathogenesis in cystic fibrosis cells","volume":"285","author":"DR Wetmore","year":"2011","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0022-3476(99)70101-0","article-title":"Decreased levels of nitrosothiols in the lower airways of the patients with cystic fibrosis and normal pulmanory function","volume":"135","author":"H Grasemann","year":"1999","journal-title":"J Pediatr"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.toxlet.2007.05.021","article-title":"The use of metabolomics for the discovery of new biomarkers of effect","volume":"172","author":"B van Ravenzwaay","year":"2007","journal-title":"Toxicol Lett"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/0192623309332992","article-title":"Discovery of metabolomics biomarkers for early detection of nephrotoxicity","volume":"37","author":"KJ Boudonck","year":"2009","journal-title":"Toxicol Pathol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"16768","DOI":"10.1074\/jbc.M601876200","article-title":"Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption","volume":"281","author":"T Soga","year":"2006","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11306-008-0153-z","article-title":"Validation of metabolomics for toxic mechanism of action screening with the earthworm Lumbricus rubellus","volume":"5","author":"Q Guo","year":"2009","journal-title":"Metabolomics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1105\/tpc.13.1.11","article-title":"Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems","volume":"13","author":"U Roessner","year":"2001","journal-title":"Plant Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/mp\/ssr114","article-title":"Drought responses of leaf tissues from wheat cultivars of differing drought tolerance at the metabolite level","volume":"5","author":"JB Bowne","year":"2011","journal-title":"Mol Plant"},{"key":"ref14","article-title":"Comparative methods for association studies: a case study on metabolite variation in a brassica rapa core collection","author":"D Pino Del Carpio","year":"2011","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"7809","DOI":"10.1073\/pnas.0303415101","article-title":"Differential metabolic networks unravel the effects of silent plant phenotypes","volume":"101","author":"W Weckwerth","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1093\/bioinformatics\/17.12.1198","article-title":"Visualizing plant metabolomic correlation networks using clique-metabolite matrices","volume":"17","author":"F Kose","year":"2001","journal-title":"Bioinformatics"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1126\/science.277.5330.1275","article-title":"A test case of correlation metric construction of a reaction pathway from measurements","volume":"277","author":"A Arkin","year":"1997","journal-title":"Science"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/bib\/bbl009","article-title":"On the analysis and interpretation of correlations in metabolomic data","volume":"7","author":"R Steuer","year":"2006","journal-title":"Brief Bioinform"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11306-005-1107-3","article-title":"The origin of correlations in metabolomics data","volume":"1","author":"D Camacho","year":"2005","journal-title":"Metabolomics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0031-9422(02)00705-7","article-title":"Assessment of 1H NMR spectroscopy and multivariate analysis as a technique for metabolite fingerprinting of Arabidopsis thaliana","volume":"62","author":"JL Ward","year":"2003","journal-title":"Phytochemistry"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/toxsci\/kfq004","article-title":"Discovery of metabolic signatures for predicting whole organism toxicology","volume":"115","author":"A Hines","year":"2010","journal-title":"Toxicol Sci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/bioinformatics\/bth270","article-title":"Metabolite fingerprinting: detecting biological features by independent component analysis","volume":"20","author":"M Scholz","year":"2004","journal-title":"Bioinformatics"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1399-3054.2007.01006.x","article-title":"Metabolite profile analysis: from raw data to regression and classification","volume":"132","author":"M Steinfath","year":"2008","journal-title":"Physiol Plant"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/aic.690370209","article-title":"Nonlinear principal component analysis using autoassociative neural networks","volume":"37","author":"MA Kramer","year":"1991","journal-title":"AIChE J"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1093\/bioinformatics\/bti634","article-title":"Non-linear PCA: a missing data approach","volume":"21","author":"M Scholz","year":"2005","journal-title":"Bioinformatics"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ki.1991.159","article-title":"Additive and synergistic effects of cyclosporine metabolites on glomerular mesangial cells","volume":"39","author":"HH Radeke","year":"1991","journal-title":"Kidney Int"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1203\/PDR.0b013e3181b4e8d3","article-title":"Persistence of essential fatty acid deficiency in cystic fibrosis despite nutritional therapy","volume":"66","author":"L Ald\u00e1miz-Echevarr\u00eda","year":"2009","journal-title":"Pediatr Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1373\/clinchem.2006.077008","article-title":"Potential utility of plasma fatty acid analysis in the diagnosis of cystic fibrosis","volume":"53","author":"I Batal","year":"2006","journal-title":"Clin Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nprot.2011.319","article-title":"Web-based inference of biological patterns, functions and pathways from metabolomic data using MetaboAnalyst","volume":"6","author":"J Xia","year":"2011","journal-title":"Nat Protoc"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1101\/gr.6202607","article-title":"A systems biology approach for pathway level analysis","volume":"17","author":"S Draghici","year":"2007","journal-title":"Genome Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1089\/cmb.2010.0269","article-title":"Subnetwork State Functions Define Dysregulated Subnetworks in Cancer","volume":"18","author":"SA Chowdhury","year":"2010","journal-title":"J Comput Biol"},{"key":"ref33","article-title":"MIClique: An Algorithm to Identify Differentially Coexpressed Disease Gene Subset from Microarray Data","author":"H Zhang","year":"2009","journal-title":"J Biomed Biotechnol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1016\/j.patcog.2010.03.002","article-title":"MIB: Using mutual information for biclustering gene expression data","volume":"43","author":"N Gupta","year":"2010","journal-title":"Pattern Recognit"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"S231","DOI":"10.1093\/bioinformatics\/18.suppl_2.S231","article-title":"The mutual information: Detecting and evaluating dependencies between variables","volume":"18","author":"R Steuer","year":"2002","journal-title":"Bioinformatics"},{"key":"ref36","first-page":"415","article-title":"Mutual information relevance networks: Functional genomic clustering using pairwise entropy measurements","volume":"5","author":"AJ Butte","year":"2000","journal-title":"Pac Symp Biocomput"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s11306-009-0156-4","article-title":"Metabolic network discovery through reverse engineering of metabolome data","volume":"5","author":"T Cak\u0131r","year":"2009","journal-title":"Metabolomics"},{"key":"ref38","first-page":"112","article-title":"Measuring correlations in the metabolic network with mutual information","volume":"20","author":"J Numata","year":"2008","journal-title":"Genome Inform"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1103\/PhysRevE.52.2318","article-title":"Estimation of mutual information using kernel density estimators","volume":"52","author":"YI Moon","year":"1995","journal-title":"Phys Rev E"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Silwerman BW (1986) Density estimation for statistics and data analysis. London: Chapman and Hall.","DOI":"10.1007\/978-1-4899-3324-9"},{"key":"ref41","article-title":"A New Metabolomics Analysis Technique: Steady State Metabolic Network Dynamics Analysis","author":"A Cakmak","year":"2012","journal-title":"J Bioinform Comput Biol"},{"key":"ref42","article-title":"Observation Conflict Resolution in Steady State Metabolic Network Dynamics Analysis","author":"AE Cicek","year":"2012","journal-title":"J Bioinform Comput Biol"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"DeBoor C (1978) A practical guide to splines. New York: Springer.","DOI":"10.1007\/978-1-4612-6333-3"},{"key":"ref44","article-title":"Estimating mutual information using B-spline functions \u2013 an improved similarity measure for analysing gene expression data","author":"CO Daub","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-642-12368-9_2","article-title":"Efficient entropy estimation for mutual information analysis using B-splines","volume":"6033","author":"A Venelli","year":"2010","journal-title":"Lect Notes Comput Sc"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1142\/S0218339094000131","article-title":"On elementary flux modes in biochemical reaction systems at steady state","volume":"2","author":"S Schuster","year":"1994","journal-title":"J Biol Syst"},{"key":"ref47","article-title":"Altered de novo lipogenesis contributes to low adipose stores in cystic fibrosis mice","author":"I Bederman","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref48","article-title":"YANA \u2013 a software tool for analyzing flux modes, gene-expression and enzyme activities","author":"R Schwarz","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"ref49","unstructured":"Selway JG (2004) Metabolism at A Glance. Wiley-Blackwell."},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.2772657","article-title":"Identification of cystic fibrosis gene: Chromosome walking and jumping","volume":"245","author":"JM Rommens","year":"1989","journal-title":"Science"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1126\/science.257.5073.1083","article-title":"An animal model for cystic fibrosis made by gene targeting","volume":"257","author":"JN Snouwaert","year":"1992","journal-title":"Science"},{"key":"ref52","unstructured":"Guyton A, Hall J (1991) Medical Physiology. Philadelphia: Elsevier Saunders. pp. 771\u2013774."},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nbt.1487","article-title":"Network-based prediction of human tissue-specific metabolism","volume":"26","author":"T Shlomi","year":"2008","journal-title":"Nat Biotechnol"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Dubitzky W, Granzow M, Berrar DP (2007) Fundamentals of data mining in genomics and proteomics. New York: Springer.","DOI":"10.1007\/978-0-387-47509-7"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA data mining software: An update","volume":"11","author":"M Hall","year":"2009","journal-title":"ACM SIGKDD Explorations Newsletter"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"9177","DOI":"10.1021\/ac101216e","article-title":"Evaluation of peak picking in LC-MS metabolomics data","volume":"82","author":"L Brodsky","year":"2010","journal-title":"Anal Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S0006-3495(00)76672-0","article-title":"Transduction of intracellular and intercellular dynamics in yeast glycolytic oscillations","volume":"78","author":"J Wolf","year":"2000","journal-title":"Biophys J"},{"key":"ref58","article-title":"BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models","author":"C Li","year":"2010","journal-title":"BMC Syst Biol"},{"key":"ref59","article-title":"PathCase-SB architecture and database design","author":"A Cakmak","year":"2011","journal-title":"BMC Syst Biol"},{"key":"ref60","article-title":"PathCase-SB: integrating data sources and providing tools for systems biology research","author":"SA Coskun","year":"2012","journal-title":"BMC Systems Biology"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/imammb\/20.1.105","article-title":"A mathematical model of lipid-mediated thrombin generation","volume":"20","author":"SD Bungay","year":"2003","journal-title":"Math Med Biol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1016\/j.febslet.2008.05.026","article-title":"Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk","volume":"582","author":"CY Ung","year":"2008","journal-title":"FEBS Lett"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1006\/mgme.2001.3170","article-title":"Quantitative determination of plasma c8\u2013c26 total fatty acids for the biochemical diagnosis of nutritional and metabolic disorders","volume":"73","author":"SA Lagerstedt","year":"2001","journal-title":"Mol Genet Metab"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A CFTR potentiator in patients with cystic fibrosis and the G551D mutation","volume":"365","author":"BW Ramsey","year":"2011","journal-title":"N Engl J Med"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.clinbiochem.2007.01.002","article-title":"An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis","volume":"40","author":"TC Coste","year":"2007","journal-title":"Clin Biochem"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T14:54:06Z","timestamp":1539960846000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002859"}},"subtitle":[],"editor":[{"given":"Jason A.","family":"Papin","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,1,17]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,1,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002859","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,17]]}}}