{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T12:22:57Z","timestamp":1754482977834},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cheminform"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>An important step in the reconstruction of a metabolic network is annotation of metabolites. Metabolites are generally annotated with various database or structure based identifiers. Metabolite annotations in metabolic reconstructions may be incorrect or incomplete and thus need to be updated prior to their use. Genome-scale metabolic reconstructions generally include hundreds of metabolites. Manually updating annotations is therefore highly laborious. This prompted us to look for open-source software applications that could facilitate automatic updating of annotations by mapping between available metabolite identifiers. We identified three applications developed for the metabolomics and chemical informatics communities as potential solutions. The applications were MetMask, the Chemical Translation System, and UniChem. The first implements a \u201cmetabolite masking\u201d strategy for mapping between identifiers whereas the latter two implement different versions of an InChI based strategy. Here we evaluated the suitability of these applications for the task of mapping between metabolite identifiers in genome-scale metabolic reconstructions. We applied the best suited application to updating identifiers in Recon 2, the latest reconstruction of human metabolism.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>All three applications enabled partially automatic updating of metabolite identifiers, but significant manual effort was still required to fully update identifiers. We were able to reduce this manual effort by searching for new identifiers using multiple types of information about metabolites. When multiple types of information were combined, the Chemical Translation System enabled us to update over 3,500 metabolite identifiers in Recon 2. All but approximately 200 identifiers were updated automatically.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We found that an InChI based application such as the Chemical Translation System was better suited to the task of mapping between metabolite identifiers in genome-scale metabolic reconstructions. We identified several features, however, that could be added to such an application in order to tailor it to this task.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1758-2946-6-2","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T12:02:43Z","timestamp":1390824163000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Comparative evaluation of open source software for mapping between metabolite identifiers in metabolic network reconstructions: application to Recon 2"],"prefix":"10.1186","volume":"6","author":[{"given":"Hulda S","family":"Haraldsd\u00f3ttir","sequence":"first","affiliation":[]},{"given":"Ines","family":"Thiele","sequence":"additional","affiliation":[]},{"given":"Ronan MT","family":"Fleming","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"492_CR1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511790515","volume-title":"Systems Biology: Properties of Reconstructed Networks, 1st edn","author":"B\u00d8 Palsson","year":"2006","unstructured":"Palsson B\u00d8: Systems Biology: Properties of Reconstructed Networks, 1st edn. 2006, Cambridge: Cambridge University Press"},{"issue":"1","key":"492_CR2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/nprot.2009.203","volume":"5","author":"I Thiele","year":"2010","unstructured":"Thiele I, Palsson B\u00d8: A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc. 2010, 5 (1): 93-121.","journal-title":"Nat Protoc"},{"key":"492_CR3","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1038\/msb4100074","volume":"2","author":"A K\u00fcmmel","year":"2006","unstructured":"K\u00fcmmel A, Panke S, Heinemann M: Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Mol Syst Biol. 2006, 2: 2006-2034.","journal-title":"Mol Syst Biol"},{"issue":"2","key":"492_CR4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1042\/BJ20120980","volume":"449","author":"\u00d3 Rolfsson","year":"2013","unstructured":"Rolfsson \u00d3, Paglia G, Magn\u00fasd\u00f3ttir M, Palsson B\u00d8, Thiele I: Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity. Biochem J. 2013, 449 (2): 427-435.","journal-title":"Biochem J"},{"key":"492_CR5","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/msb.2011.35","volume":"7","author":"O Folger","year":"2011","unstructured":"Folger O, Jerby L, Frezza C, Gottlieb E, Ruppin E, Shlomi T: Predicting selective drug targets in cancer through metabolic networks. Mol Syst Biol. 2011, 7: 501-","journal-title":"Mol Syst Biol"},{"issue":"10","key":"492_CR6","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1039\/c2mb25075f","volume":"8","author":"S Sahoo","year":"2012","unstructured":"Sahoo S, Franzson L, Jonsson JJ, Thiele I: A compendium of inborn errors of metabolism mapped onto the human metabolic network. Mol BioSyst. 2012, 8 (10): 2545-2558.","journal-title":"Mol BioSyst"},{"issue":"1","key":"492_CR7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.4161\/gmic.22370","volume":"4","author":"A Heinken","year":"2013","unstructured":"Heinken A, Sahoo S, Fleming RMT, Thiele I: Systems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut. Gut Microbes. 2013, 4 (1): 28-40.","journal-title":"Gut Microbes"},{"issue":"7","key":"492_CR8","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nchembio.580","volume":"7","author":"H Yim","year":"2011","unstructured":"Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick JD, Osterhout RE, Stephen R, Estadilla J, Teisan S, Schreyer HB, Andrae S, Yang TH, Lee SY, Burk MJ, Van Dien S: Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol. 2011, 7 (7): 445-452.","journal-title":"Nat Chem Biol"},{"issue":"1","key":"492_CR9","doi-asserted-by":"publisher","first-page":"54144","DOI":"10.1371\/journal.pone.0054144","volume":"8","author":"JM Otero","year":"2013","unstructured":"Otero JM, Cimini D, Patil KR, Poulsen SG, Olsson L, Nielsen J: Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory. PLoS One. 2013, 8 (1): 54144-","journal-title":"PLoS One"},{"issue":"Database issue","key":"492_CR10","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1093\/nar\/gks1146","volume":"41","author":"J Hastings","year":"2013","unstructured":"Hastings J, de Matos P, Dekker A, Ennis M, Harsha B, Kale N, Muthukrishnan V, Owen G, Turner S, Williams M, Steinbeck C: The ChEBI reference database and ontology for biologically relevant chemistry: enhancements for 2013. Nucleic Acids Res. 2013, 41 (Database issue): 456-463.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"492_CR11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M: KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 2000, 28 (1): 27-30.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"492_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/nar\/gkr988","volume":"40","author":"M Kanehisa","year":"2012","unstructured":"Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M: KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 2012, 40 (Database issue): 109-114.","journal-title":"Nucleic Acids Res"},{"key":"492_CR13","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S1574-1400(08)00012-1","volume":"4","author":"EE Bolton","year":"2008","unstructured":"Bolton EE, Wang Y, Thiessen PA, Bryant SH: PubChem: integrated platform of small molecules and biological activities. Annu Rep Comput Chem. 2008, 4: 217-241. Chap. 12.","journal-title":"Annu Rep Comput Chem"},{"issue":"Database issue","key":"492_CR14","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1093\/nar\/gkl923","volume":"35","author":"DS Wishart","year":"2007","unstructured":"Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S, Fung C, Nikolai L, Lewis M, Coutouly M-A, Forsythe I, Tang P, Shrivastava S, Jeroncic K, Stothard P, Amegbey G, Block D, Hau DD, Wagner J, Miniaci J, Clements M, Gebremedhin M, Guo N, Zhang Y, Duggan GE, Macinnis GD, et al: HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007, 35 (Database issue): 521-526.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"492_CR15","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/nar\/gks1065","volume":"41","author":"DS Wishart","year":"2013","unstructured":"Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A: HMDB 3.0\u2013The Human Metabolome Database in 2013. Nucleic Acids Res. 2013, 41 (Database issue): 801-807.","journal-title":"Nucleic Acids Res"},{"issue":"50","key":"492_CR16","doi-asserted-by":"publisher","first-page":"16487","DOI":"10.1021\/ja0466457","volume":"126","author":"M Kotera","year":"2004","unstructured":"Kotera M, Okuno Y, Hattori M, Goto S, Kanehisa M: Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions. J Am Chem Soc. 2004, 126 (50): 16487-16498.","journal-title":"J Am Chem Soc"},{"issue":"1","key":"492_CR17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ymben.2006.09.001","volume":"9","author":"MR Antoniewicz","year":"2007","unstructured":"Antoniewicz MR, Kelleher JK, Stephanopoulos G: Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions. Metab Eng. 2007, 9 (1): 68-86.","journal-title":"Metab Eng"},{"issue":"1","key":"492_CR18","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1021\/ci200351b","volume":"52","author":"EL First","year":"2012","unstructured":"First EL, Gounaris CE, Floudas CA: Stereochemically consistent reaction mapping and identification of multiple reaction mechanisms through integer linear optimization. J Chem Inf Model. 2012, 52 (1): 84-92.","journal-title":"J Chem Inf Model"},{"issue":"7","key":"492_CR19","doi-asserted-by":"publisher","first-page":"1003098","DOI":"10.1371\/journal.pcbi.1003098","volume":"9","author":"E Noor","year":"2013","unstructured":"Noor E, Haraldsd\u00f3ttir HS, Milo R, Fleming RMT: Consistent estimation of Gibbs energy using component contributions. PLoS Comput Biol. 2013, 9 (7): 1003098-","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"492_CR20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1758-2946-5-7","volume":"5","author":"S Heller","year":"2013","unstructured":"Heller S, McNaught A, Stein S, Tchekhovskoi D, Pletnev I: InChI - the worldwide chemical structure identifier standard. J Cheminf. 2013, 5 (1): 7-","journal-title":"J Cheminf"},{"key":"492_CR21","unstructured":"Chemical Identifier Resolver. http:\/\/cactus.nci.nih.gov\/chemical\/structure,"},{"key":"492_CR22","unstructured":"ChemSpider. http:\/\/www.chemspider.com\/,"},{"issue":"5","key":"492_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nbt.2488","volume":"31","author":"I Thiele","year":"2013","unstructured":"Thiele I, Swainston N, Fleming RMT, Hoppe A, Sahoo S, Aurich MK, Haraldsd\u00f3ttir HS, Mo ML, Rolfsson \u00d3, Stobbe MD, Thorleifsson SG, Agren R, B\u00f6lling C, Bordel S, Chavali AK, Dobson P, Dunn WB, Endler L, Hala D, Hucka M, Hull D, Jameson D, Jamshidi N, Jonsson JJ, Juty N, Keating S, Nookaew I, Le Nov\u00e8re N, Malys N, et al: A community-driven global reconstruction of human metabolism. Nat Biotechnol. 2013, 31 (5): 419-425.","journal-title":"Nat Biotechnol"},{"issue":"9","key":"492_CR24","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/nbt.1672","volume":"28","author":"CS Henry","year":"2010","unstructured":"Henry CS, DeJongh M, Best AA, Frybarger PM, Linsay B, Stevens RL: High-throughput generation, optimization and analysis of genome-scale metabolic models. Nat Biotechnol. 2010, 28 (9): 977-982.","journal-title":"Nat Biotechnol"},{"issue":"14","key":"492_CR25","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1093\/bioinformatics\/btr308","volume":"27","author":"SG Thorleifsson","year":"2011","unstructured":"Thorleifsson SG, Thiele I: rBioNet: A COBRA toolbox extension for reconstructing high-quality biochemical networks. Bioinformatics (Oxford, England). 2011, 27 (14): 2009-2010.","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"2","key":"492_CR26","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1515\/jib-2011-186","volume":"8","author":"N Swainston","year":"2011","unstructured":"Swainston N, Smallbone K, Mendes P, Kell D, Paton N: The SuBliMinaL Toolbox: automating steps in the reconstruction of metabolic networks. J Integr Bioinform. 2011, 8 (2): 186-","journal-title":"J Integr Bioinform"},{"issue":"17","key":"492_CR27","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1093\/bioinformatics\/btt342","volume":"29","author":"JW May","year":"2013","unstructured":"May JW, James AG, Steinbeck C: Metingear: a development environment for annotating genome-scale metabolic models. Bioinformatics (Oxford, England). 2013, 29 (17): 2213-2215.","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"13\u201314","key":"492_CR28","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.drudis.2012.02.013","volume":"17","author":"AJ Williams","year":"2012","unstructured":"Williams AJ, Ekins S, Tkachenko V: Towards a gold standard: regarding quality in public domain chemistry databases and approaches to improving the situation. Drug Discovery Today. 2012, 17 (13\u201314): 685-701.","journal-title":"Drug Discovery Today"},{"key":"492_CR29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/1471-2105-11-214","volume":"11","author":"H Redestig","year":"2010","unstructured":"Redestig H, Kusano M, Fukushima A, Matsuda F, Saito K, Arita M: Consolidating metabolite identifiers to enable contextual and multi-platform metabolomics data analysis. BMC Bioinf. 2010, 11: 214-","journal-title":"BMC Bioinf"},{"issue":"20","key":"492_CR30","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1093\/bioinformatics\/btq476","volume":"26","author":"G Wohlgemuth","year":"2010","unstructured":"Wohlgemuth G, Haldiya PK, Willighagen E, Kind T, Fiehn O: The Chemical Translation Service\u2013a web-based tool to improve standardization of metabolomic reports. Bioinformatics (Oxford, England). 2010, 26 (20): 2647-2648.","journal-title":"Bioinformatics (Oxford, England)"},{"key":"492_CR31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1758-2946-5-3","volume":"5","author":"J Chambers","year":"2013","unstructured":"Chambers J, Davies M, Gaulton A, Hersey A, Velankar S, Petryszak R, Hastings J, Bellis L, McGlinchey S, Overington JP: UniChem: a unified chemical structure cross-referencing and identifier tracking system. J Cheminf. 2013, 5: 3-","journal-title":"J Cheminf"},{"issue":"suppl 1","key":"492_CR32","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/nar\/gkl838","volume":"35","author":"M Sud","year":"2007","unstructured":"Sud M, Fahy E, Cotter D, Brown A, Dennis EA, Glass CK, Merrill AH, Murphy RC, Raetz CR, Russell DW, et al: LMSD: LIPID MAPS Structure, Database. Nucleic Acids Res. 2007, 35 (suppl 1): 527-532.","journal-title":"Nucleic Acids Res"},{"key":"492_CR33","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1758-2946-4-35","volume":"4","author":"SA Akhondi","year":"2012","unstructured":"Akhondi SA, Kors JA, Muresan S: Consistency of systematic chemical identifiers within and between small-molecule databases. J Cheminf. 2012, 4: 35-","journal-title":"J Cheminf"},{"issue":"6","key":"492_CR34","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1073\/pnas.0610772104","volume":"104","author":"NC Duarte","year":"2007","unstructured":"Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson B\u00d8: Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA. 2007, 104 (6): 1777-1782.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11\u201312","key":"492_CR35","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1002\/qsar.200810084","volume":"27","author":"D Young","year":"2008","unstructured":"Young D, Martin T, Venkatapathy R, Harten P: Are the chemical structures in your QSAR correct?. QSAR Comb Sci. 2008, 27 (11\u201312): 1337-1345.","journal-title":"QSAR Comb Sci"}],"container-title":["Journal of Cheminformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1758-2946-6-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-6-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-6-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T02:55:31Z","timestamp":1630551331000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/1758-2946-6-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,27]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["492"],"URL":"https:\/\/doi.org\/10.1186\/1758-2946-6-2","relation":{},"ISSN":["1758-2946"],"issn-type":[{"value":"1758-2946","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,27]]},"assertion":[{"value":"18 October 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"2"}}