{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:15:25Z","timestamp":1767903325355,"version":"3.49.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The metabolic network of <jats:italic>H. sapiens<\/jats:italic> and many other organisms is described in multiple pathway databases. The level of agreement between these descriptions, however, has proven to be low. We can use these different descriptions to our advantage by identifying conflicting information and combining their knowledge into a single, more accurate, and more complete description. This task is, however, far from trivial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We introduce the concept of Consensus and Conflict Cards (C<jats:sub>2<\/jats:sub>Cards) to provide concise overviews of what the databases do or do not agree on. Each card is centered at a single gene, EC number or reaction. These three complementary perspectives make it possible to distinguish disagreements on the underlying biology of a metabolic process from differences that can be explained by different decisions on how and in what detail to represent knowledge. As a proof-of-concept, we implemented C<jats:sub>2<\/jats:sub>Cards<jats:sup>Human<\/jats:sup>, as a web application <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.molgenis.org\/c2cards\" ext-link-type=\"uri\">http:\/\/www.molgenis.org\/c2cards<\/jats:ext-link>, covering five human pathway databases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>C<jats:sub>2<\/jats:sub>Cards can contribute to ongoing reconciliation efforts by simplifying the identification of consensus and conflicts between pathway databases and lowering the threshold for experts to contribute. Several case studies illustrate the potential of the C<jats:sub>2<\/jats:sub>Cards in identifying disagreements on the underlying biology of a metabolic process. The overviews may also point out controversial biological knowledge that should be subject of further research. Finally, the examples provided emphasize the importance of manual curation and the need for a broad community involvement.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-7-50","type":"journal-article","created":{"date-parts":[[2013,6,26]],"date-time":"2013-06-26T08:15:30Z","timestamp":1372234530000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Consensus and conflict cards for metabolic pathway databases"],"prefix":"10.1186","volume":"7","author":[{"given":"Miranda D","family":"Stobbe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris A","family":"Swertz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trebor","family":"Rengaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine HC","family":"van Kampen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perry D","family":"Moerland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,6,26]]},"reference":[{"key":"1102_CR1","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1007\/s00204-011-0705-2","volume":"85","author":"PD Karp","year":"2011","unstructured":"Karp PD, Caspi R: A survey of metabolic databases emphasizing the MetaCyc family. Arch Toxicol. 2011, 85: 1015-1033. 10.1007\/s00204-011-0705-2.","journal-title":"Arch Toxicol"},{"key":"1102_CR2","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/msb.2009.77","volume":"5","author":"MA Oberhardt","year":"2009","unstructured":"Oberhardt MA, Palsson B\u00d8, Papin JA: Applications of genome-scale metabolic reconstructions. Mol Syst Biol. 2009, 5: 320-","journal-title":"Mol Syst Biol"},{"key":"1102_CR3","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1038\/nbt1492","volume":"26","author":"MJ Herrg\u00e5rd","year":"2008","unstructured":"Herrg\u00e5rd MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Bl\u00fcthgen N, Borger S, Costenoble R, Heinemann M: A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nature Biotechnol. 2008, 26: 1155-1160. 10.1038\/nbt1492.","journal-title":"Nature Biotechnol"},{"key":"1102_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/1752-0509-5-165","volume":"5","author":"MD Stobbe","year":"2011","unstructured":"Stobbe MD, Houten SM, Jansen GA, van Kampen AHC, Moerland PD: Critical assessment of human metabolic pathway databases: a stepping stone for future integration. BMC Syst Biol. 2011, 5: 165-10.1186\/1752-0509-5-165.","journal-title":"BMC Syst Biol"},{"key":"1102_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.tibtech.2008.09.007","volume":"27","author":"ML Mo","year":"2009","unstructured":"Mo ML, Palsson B\u00d8: Understanding human metabolic physiology: a genome-to-systems approach. Trends Biotechnol. 2009, 27: 37-44. 10.1016\/j.tibtech.2008.09.007.","journal-title":"Trends Biotechnol"},{"key":"1102_CR6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/msb.2010.15","volume":"6","author":"I Thiele","year":"2010","unstructured":"Thiele I, Palsson B\u00d8: Reconstruction annotation jamborees: a community approach to systems biology. Mol Syst Biol. 2010, 6: 361-","journal-title":"Mol Syst Biol"},{"key":"1102_CR7","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1752-0509-5-8","volume":"5","author":"I Thiele","year":"2011","unstructured":"Thiele I, Hyduke DR, Steeb B, Fankam G, Allen DK, Bazzani S, Charusanti P, Chen FC, Fleming RM, Hsiung CA: A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2. BMC Syst Biol. 2011, 5: 8-10.1186\/1752-0509-5-8.","journal-title":"BMC Syst Biol"},{"key":"1102_CR8","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1093\/bib\/2.2.126","volume":"2","author":"U Wittig","year":"2001","unstructured":"Wittig U, De Beuckelaer A: Analysis and comparison of metabolic pathway databases. Brief Bioinform. 2001, 2: 126-142. 10.1093\/bib\/2.2.126.","journal-title":"Brief Bioinform"},{"key":"1102_CR9","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/1752-0509-4-114","volume":"4","author":"K Radrich","year":"2010","unstructured":"Radrich K, Tsuruoka Y, Dobson P, Gevorgyan A, Swainston N, Baart G, Schwartz JM: Integration of metabolic databases for the reconstruction of genome-scale metabolic networks. BMC Syst Biol. 2010, 4: 114-10.1186\/1752-0509-4-114.","journal-title":"BMC Syst Biol"},{"key":"1102_CR10","doi-asserted-by":"publisher","first-page":"R6","DOI":"10.1186\/gb-2012-13-1-r6","volume":"13","author":"L Chindelevitch","year":"2012","unstructured":"Chindelevitch L, Stanley S, Hung D, Regev A, Berger B: MetaMerge: scaling up genome-scale metabolic reconstructions, with application to Mycobacterium tuberculosis. Genome Biol. 2012, 13: R6-10.1186\/gb-2012-13-1-r6.","journal-title":"Genome Biol"},{"key":"1102_CR11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/1471-2105-11-213","volume":"11","author":"J Schellenberger","year":"2010","unstructured":"Schellenberger J, Park JO, Conrad TM, Palsson B\u00d8: BiGG: a Biochemical Genetic and Genomic knowledgebase of large scale metabolic reconstructions. BMC Bioinforma. 2010, 11: 213-10.1186\/1471-2105-11-213.","journal-title":"BMC Bioinforma"},{"key":"1102_CR12","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: 1777-1782. 10.1073\/pnas.0610772104.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1102_CR13","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1186\/1471-2105-11-393","volume":"11","author":"T Hao","year":"2010","unstructured":"Hao T, Ma HW, Zhao XM, Goryanin I: Compartmentalization of the Edinburgh Human Metabolic Network. BMC Bioinforma. 2010, 11: 393-10.1186\/1471-2105-11-393.","journal-title":"BMC Bioinforma"},{"key":"1102_CR14","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1186\/gb-2004-6-1-r2","volume":"6","author":"P Romero","year":"2004","unstructured":"Romero P, Wagg J, Green ML, Kaiser D, Krummenacker M, Karp PD: Computational prediction of human metabolic pathways from the complete human genome. Genome Biol. 2004, 6: R2-10.1186\/gb-2004-6-1-r2.","journal-title":"Genome Biol"},{"key":"1102_CR15","doi-asserted-by":"publisher","first-page":"D109","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. Nucl Acids Res. 2012, 40: D109-D114. 10.1093\/nar\/gkr988.","journal-title":"Nucl Acids Res"},{"key":"1102_CR16","doi-asserted-by":"publisher","first-page":"D691","DOI":"10.1093\/nar\/gkq1018","volume":"39","author":"D Croft","year":"2011","unstructured":"Croft D, O\u2019Kelly G, Wu G, Haw R, Gillespie M, Matthews L, Caudy M, Garapati P, Gopinath G, Jassal B: Reactome: a database of reactions, pathways and biological processes. Nucl Acids Res. 2011, 39: D691-D697. 10.1093\/nar\/gkq1018.","journal-title":"Nucl Acids Res"},{"key":"1102_CR17","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/bit.22844","volume":"107","author":"JD Orth","year":"2010","unstructured":"Orth JD, Palsson B\u00d8: Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng. 2010, 107: 403-412. 10.1002\/bit.22844.","journal-title":"Biotechnol Bioeng"},{"key":"1102_CR18","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/gepi.20395","volume":"33","author":"CC Elbers","year":"2009","unstructured":"Elbers CC, van Eijk KR, Franke L, Mulder F, van der Schouw YT, Wijmenga C, Onland-Moret NC: Using genome-wide pathway analysis to unravel the etiology of complex diseases. Genet Epidemiol. 2009, 33: 419-431. 10.1002\/gepi.20395.","journal-title":"Genet Epidemiol"},{"key":"1102_CR19","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.abb.2004.01.018","volume":"424","author":"M Willemo\u00ebs","year":"2004","unstructured":"Willemo\u00ebs M: Competition between ammonia derived from internal glutamine hydrolysis and hydroxylamine present in the solution for incorporation into UTP as catalysed by Lactococcus lactis CTP synthase. Arch Biochem Biophys. 2004, 424: 105-111. 10.1016\/j.abb.2004.01.018.","journal-title":"Arch Biochem Biophys"},{"key":"1102_CR20","doi-asserted-by":"publisher","first-page":"33727","DOI":"10.1074\/jbc.M110.178566","volume":"285","author":"KM Kassel","year":"2010","unstructured":"Kassel KM, Au DR, Higgins MJ, Hines M, Graves LM: Regulation of Human Cytidine Triphosphate Synthetase 2 by Phosphorylation. J Biol Chem. 2010, 285: 33727-33736. 10.1074\/jbc.M110.178566.","journal-title":"J Biol Chem"},{"key":"1102_CR21","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.2217\/14622416.8.9.1221","volume":"8","author":"J Bierau","year":"2007","unstructured":"Bierau J, Lindhout M, Bakker JA: Pharmacogenetic significance of inosine triphosphatase. Pharmacogenomics. 2007, 8: 1221-1228. 10.2217\/14622416.8.9.1221.","journal-title":"Pharmacogenomics"},{"key":"1102_CR22","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/S0006-291X(03)01062-3","volume":"307","author":"M Johansson","year":"2003","unstructured":"Johansson M: Identification of a novel human uridine phosphorylase. Biochem Biophys Res Commun. 2003, 307: 41-46. 10.1016\/S0006-291X(03)01062-3.","journal-title":"Biochem Biophys Res Commun"},{"key":"1102_CR23","first-page":"3687","volume":"53","author":"MH el Kouni","year":"1993","unstructured":"el Kouni MH, el Kouni MM, Naguib FNM: Differences in Activities and Substrate Specificity of Human and Murine Pyrimidine Nucleoside Phosphorylases: Implications for Chemotherapy with 5-Fluoropyrimidines. Cancer Res. 1993, 53: 3687-3693.","journal-title":"Cancer Res"},{"key":"1102_CR24","doi-asserted-by":"publisher","first-page":"D712","DOI":"10.1093\/nar\/gkq1156","volume":"39","author":"A Kamburov","year":"2011","unstructured":"Kamburov A, Pentchev K, Galicka H, Wierling C, Lehrach H, Herwig R: ConsensusPathDB: toward a more complete picture of cell biology. Nucl Acids Res. 2011, 39: D712-D717. 10.1093\/nar\/gkq1156.","journal-title":"Nucl Acids Res"},{"key":"1102_CR25","doi-asserted-by":"publisher","first-page":"D685","DOI":"10.1093\/nar\/gkq1039","volume":"39","author":"EG Cerami","year":"2011","unstructured":"Cerami EG, Gross BE, Demir E, Rodchenkov I, Babur O, Anwar N, Schultz N, Bader GD, Sander C: Pathway commons, a web resource for biological pathway data. Nucl Acids Res. 2011, 39: D685-D690. 10.1093\/nar\/gkq1039.","journal-title":"Nucl Acids Res"},{"key":"1102_CR26","doi-asserted-by":"publisher","first-page":"D196","DOI":"10.1093\/nar\/gkp931","volume":"38","author":"G \u00d6stlund","year":"2010","unstructured":"\u00d6stlund G, Schmitt T, Forslund K, K\u00f6stler T, Messina DN, Roopra S, Frings O, Sonnhammer ELL: InParanoid 7: new algorithms and tools for eukaryotic orthology analysis. Nucl Acids Res. 2010, 38: D196-D203. 10.1093\/nar\/gkp931.","journal-title":"Nucl Acids Res"},{"key":"1102_CR27","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, Haraldsdottir H, Mo ML, Rolfsson O, Stobbe MD: A community-driven global reconstruction of human metabolism. Nat Biotech. 2013, 31: 419-425. 10.1038\/nbt.2488.","journal-title":"Nat Biotech"},{"key":"1102_CR28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/ISU-2010-0613","volume":"30","author":"P Groth","year":"2010","unstructured":"Groth P, Gibson A, Velterop J: The anatomy of a nanopublication. Information Services and Use. 2010, 30: 51-56.","journal-title":"Information Services and Use"},{"key":"1102_CR29","doi-asserted-by":"publisher","first-page":"e184","DOI":"10.1371\/journal.pbio.0060184","volume":"6","author":"AR Pico","year":"2008","unstructured":"Pico AR, Kelder T, van Iersel MP, Hanspers K, Conklin BR, Evelo C: WikiPathways: pathway editing for the people. PLoS Biol. 2008, 6: e184-10.1371\/journal.pbio.0060184.","journal-title":"PLoS Biol"},{"key":"1102_CR30","doi-asserted-by":"publisher","first-page":"4035","DOI":"10.1093\/nar\/gki711","volume":"33","author":"ML Green","year":"2005","unstructured":"Green ML, Karp PD: Genome annotation errors in pathway databases due to semantic ambiguity in partial EC numbers. Nucleic Acids Res. 2005, 33: 4035-4039. 10.1093\/nar\/gki711.","journal-title":"Nucleic Acids Res"},{"key":"1102_CR31","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1186\/1471-2105-11-S12-S12","volume":"11","author":"MA Swertz","year":"2010","unstructured":"Swertz MA, Dijkstra M, Adamusiak T, van der Velde JK, Kanterakis A, Roos TE, Lops J, Thorisson GA, Arends D, Byelas G: The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button. BMC Bioinforma. 2010, 11: S12-","journal-title":"BMC Bioinforma"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-7-50.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:51:05Z","timestamp":1630543865000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-7-50"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,26]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1102"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-7-50","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,26]]},"assertion":[{"value":"23 October 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"50"}}