{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:42:52Z","timestamp":1783993372480,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classifying and predicting enzymatic reactions. However, numerous reactions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified enzymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified.<\/jats:p>\n               <jats:p>Results: We propose a new method to assign EC numbers using a maximum common substructure algorithm, mutual information and a support vector machine, termed the Enzyme COmmission numbers Handler (ECOH). A jack-knife test shows that the sensitivity, precision and accuracy of the method in predicting the first three digits of the official EC number (i.e. the EC sub-subclass) are 86.1%, 87.4% and 99.8%, respectively. We furthermore demonstrate that, by examining the ranking in the candidate lists of EC sub-subclasses generated by the algorithm, the method can successfully predict the classification of 85 enzymatic reactions that fall into multiple EC sub-subclasses. The better performance of the ECOH as compared with existing methods and its flexibility in predicting EC numbers make it useful for predicting enzyme function.<\/jats:p>\n               <jats:p>Availability: ECOH is freely available via the Internet at http:\/\/www.bioinfo.sk.ritsumei.ac.jp\/apps\/ecoh\/. This program only works on 32-bit Windows.<\/jats:p>\n               <jats:p>Contact: \u00a0yukako@sk.ritsumei.ac.jp<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts700","type":"journal-article","created":{"date-parts":[[2012,12,8]],"date-time":"2012-12-08T08:17:38Z","timestamp":1354954658000},"page":"365-372","source":"Crossref","is-referenced-by-count":34,"title":["ECOH: An Enzyme Commission number predictor using mutual information and a support vector machine"],"prefix":"10.1093","volume":"29","author":[{"given":"Yoshihiko","family":"Matsuta","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Tohsato","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,5]]},"reference":[{"key":"2023012810221987500_bts700-B1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cbpa.2011.03.008","article-title":"Toward mechanistic classification of enzyme functions","volume":"15","author":"Almonacid","year":"2011","journal-title":"Curr. Opin. Chem. Biol."},{"key":"2023012810221987500_bts700-B2","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkm993","article-title":"Data growth and its impact on the SCOP database: new developments","volume":"36","author":"Andreeva","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023012810221987500_bts700-B3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"2023012810221987500_bts700-B4","doi-asserted-by":"crossref","first-page":"30591","DOI":"10.1074\/jbc.272.49.30591","article-title":"Understanding enzyme superfamilies. Chemistry as the fundamental determinant in the evolution of new catalytic activities","volume":"272","author":"Babbitt","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023012810221987500_bts700-B5","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.jmb.2008.11.057","article-title":"Sequence and structural features of enzymes and their active sites by EC Class","volume":"386","author":"Bray","year":"2009","journal-title":"J. Mol. Biol."},{"key":"2023012810221987500_bts700-B6","doi-asserted-by":"crossref","first-page":"i366","DOI":"10.1093\/bioinformatics\/btn186","article-title":"A maximum common substructure-based algorithm for searching and predicting drug-like compounds","volume":"24","author":"Cao","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012810221987500_bts700-B7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1145\/1961189.1961199","article-title":"LIBSVM: a library for support vector machines","volume":"2","author":"Chang","year":"2011","journal-title":"ACM Trans. Intell. Syst. Technol."},{"key":"2023012810221987500_bts700-B8","doi-asserted-by":"crossref","first-page":"D420","DOI":"10.1093\/nar\/gkq1001","article-title":"Extending CATH: increasing coverage of the protein structure universe and linking structure with function","volume":"39","author":"Cuff","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023012810221987500_bts700-B11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1471-2105-13-61","article-title":"EnzML: Multi-label prediction of enzyme classes using InterPro signatures","volume":"13","author":"De Ferrari","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2023012810221987500_bts700-B9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jmb.2004.10.024","article-title":"Predicting enzyme class from protein structure without alignments","volume":"345","author":"Dobson","year":"2005","journal-title":"J. Mol. Biol."},{"key":"2023012810221987500_bts700-B10","doi-asserted-by":"crossref","first-page":"e1000661","DOI":"10.1371\/journal.pcbi.1000661","article-title":"Automatic assignment of EC numbers","volume":"6","author":"Egelhofer","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"2023012810221987500_bts700-B12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nchembio0809-521","article-title":"Missing in action: Enzyme functional annotations in biological databases","volume":"5","author":"Furnham","year":"2009","journal-title":"Nature Chemical Biology"},{"key":"2023012810221987500_bts700-B13","first-page":"1157","article-title":"An introduction to variable and feature selection","volume":"3","author":"Guyon","year":"2003","journal-title":"J. Mach. Learn. Res."},{"key":"2023012810221987500_bts700-B14","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1109\/TKDE.2008.239","article-title":"Learning from imbalanced data","volume":"21","author":"He","year":"2009","journal-title":"IEEE Trans. Knowl. Data Eng."},{"key":"2023012810221987500_bts700-B15","doi-asserted-by":"crossref","first-page":"D783","DOI":"10.1093\/nar\/gkr799","article-title":"MACiE: Exploring the diversity of biochemical reactions","volume":"40","author":"Holliday","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012810221987500_bts700-B16","first-page":"1","article-title":"A practical guide to support vector classification","volume":"1","author":"Hsu","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012810221987500_bts700-B17","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1021\/ci9004833","article-title":"Similarity perception of reactions catalyzed by oxidoreductases and hydrolases using different classification methods","volume":"50","author":"Hu","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"2023012810221987500_bts700-B18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1046\/j.1432-1327.1999.news99.x","article-title":"IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB), Newsletter 1999","volume":"264","author":"IUPAC-IUBMB","year":"1999","journal-title":"Eur. J Biochem."},{"key":"2023012810221987500_bts700-B19","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3233\/IDA-2002-6504","article-title":"The class imbalance problem: a systematic study","volume":"6","author":"Japkowicz","year":"2002","journal-title":"Intel. Data Anal."},{"key":"2023012810221987500_bts700-B20","doi-asserted-by":"crossref","first-page":"D109","DOI":"10.1093\/nar\/gkr988","article-title":"KEGG for integration and interpretation of large-scale molecular data sets","volume":"40","author":"Kanehisa","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023012810221987500_bts700-B21","first-page":"P062","article-title":"RPAIR: a reactant-pair database representing chemical changes in enzymatic reactions","volume":"15","author":"Kotera","year":"2004","journal-title":"Genome Informatics"},{"key":"2023012810221987500_bts700-B22","doi-asserted-by":"crossref","first-page":"16487","DOI":"10.1021\/ja0466457","article-title":"Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions","volume":"126","author":"Kotera","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"2023012810221987500_bts700-B23","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1021\/ci900104b","article-title":"Assignment of EC numbers to enzymatic reactions with MOLMAP reaction descriptors and random forests","volume":"49","author":"Latino","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"2023012810221987500_bts700-B24","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1093\/bioinformatics\/btp549","article-title":"Automatic assignment of reaction operators to enzymatic reactions","volume":"25","author":"Leber","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810221987500_bts700-B25","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.compbiolchem.2007.03.008","article-title":"ECS: an automatic enzyme classifier based on functional domain composition","volume":"31","author":"Lu","year":"2007","journal-title":"Comput. Biol. Chem."},{"key":"2023012810221987500_bts700-B26","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511809071","volume-title":"Introduction to Information Retrieval","author":"Manning","year":"2008"},{"key":"2023012810221987500_bts700-B27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1021\/ci960151e","article-title":"Clustering of large databases of compounds: using MDL \"keys\" as structural descriptors","volume":"37","author":"McGregor","year":"1997","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"2023012810221987500_bts700-B28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1471-2105-13-60","article-title":"Is EC class predictable from reaction mechanism?","volume":"13","author":"Nath","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2023012810221987500_bts700-B29","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1021\/ci800277f","article-title":"Investigations of enzyme-catalyzed reactions based on physicochemical descriptors applied to hydrolases","volume":"49","author":"Sacher","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"2023012810221987500_bts700-B30","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1186\/1471-2105-11-S1-S31","article-title":"Reaction graph kernels predict EC numbers of unknown enzymatic reactions in plant secondary metabolism","volume":"11","author":"Saigo","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023012810221987500_bts700-B31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1021\/ci025584y","article-title":"The Chemistry Development Kit (CDK): an open-source Java library for chemo- and bioinformatics","volume":"43","author":"Steinbeck","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"2023012810221987500_bts700-B32","first-page":"376","article-title":"A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchy","volume":"2000","author":"Tohsato","year":"2000","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol."},{"key":"2023012810221987500_bts700-B33","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0898-5529(90)90061-C","article-title":"Machine learning of generic reactions: 3. An efficient algorithm for maximal common substructure determination","volume":"3","author":"Tonnelier","year":"1991","journal-title":"Tetrahedron Comput. Methodol."},{"key":"2023012810221987500_bts700-B34","volume-title":"Statistical Learning Theory","author":"Vapnik","year":"1998"},{"key":"2023012810221987500_bts700-B35","first-page":"4275","article-title":"Prediction of silicon content in hot metal based on SVM and mutual information for feature selection","volume":"8","author":"Wang","year":"2011","journal-title":"J. Inf. Comput. Sci."},{"key":"2023012810221987500_bts700-B36","doi-asserted-by":"crossref","first-page":"i179","DOI":"10.1093\/bioinformatics\/btp223","article-title":"E-zyme: Predicting potential EC numbers from the chemical transformation pattern of substrate-product pairs","volume":"25","author":"Yamanishi","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810221987500_bts700-B37","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1504\/IJDMB.2011.041555","article-title":"MAPLSC: A novel multi-class classifier for medical diagnosis","volume":"5","author":"You","year":"2011","journal-title":"Int. J. Data Min. Bioinf."},{"key":"2023012810221987500_bts700-B38","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/prot.22167","article-title":"Genome-wide enzyme annotation with precision control: Catalytic families (CatFam) databases","volume":"74","author":"Yu","year":"2009","journal-title":"Proteins"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/3\/365\/48894320\/bioinformatics_29_3_365.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/3\/365\/48894320\/bioinformatics_29_3_365.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T11:48:51Z","timestamp":1674906531000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/29\/3\/365\/257645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,5]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts700","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,2,1]]},"published":{"date-parts":[[2012,12,5]]}}}