{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:37:53Z","timestamp":1771000673291,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,28]],"date-time":"2016-10-28T00:00:00Z","timestamp":1477612800000},"content-version":"vor","delay-in-days":139,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation : Metabolic pathways are an important class of molecular networks consisting of compounds, enzymes and their interactions. The understanding of global metabolic pathways is extremely important for various applications in ecology and pharmacology. However, large parts of metabolic pathways remain unknown, and most organism-specific pathways contain many missing enzymes. Results: In this study we propose a novel method to predict the enzyme orthologs that catalyze the putative reactions to facilitate the de novo reconstruction of metabolic pathways from metabolome-scale compound sets. The algorithm detects the chemical transformation patterns of substrate\u2013product pairs using chemical graph alignments, and constructs a set of enzyme-specific classifiers to simultaneously predict all the enzyme orthologs that could catalyze the putative reactions of the substrate\u2013product pairs in the joint learning framework. The originality of the method lies in its ability to make predictions for thousands of enzyme orthologs simultaneously, as well as its extraction of enzyme-specific chemical transformation patterns of substrate\u2013product pairs. We demonstrate the usefulness of the proposed method by applying it to some ten thousands of metabolic compounds, and analyze the extracted chemical transformation patterns that provide insights into the characteristics and specificities of enzymes. The proposed method will open the door to both primary (central) and secondary metabolism in genomics research, increasing research productivity to tackle a wide variety of environmental and public health matters.<\/jats:p>\n               <jats:p>Availability and Implementation :<\/jats:p>\n               <jats:p>Contact : maskot@bio.titech.ac.jp<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw260","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T15:43:52Z","timestamp":1466005432000},"page":"i278-i287","source":"Crossref","is-referenced-by-count":16,"title":["Simultaneous prediction of enzyme orthologs from chemical transformation patterns for \n            <i>de novo<\/i>\n             metabolic pathway reconstruction"],"prefix":"10.1093","volume":"32","author":[{"given":"Yasuo","family":"Tabei","sequence":"first","affiliation":[{"name":"1 PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan"},{"name":"\u2020 The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Yamanishi","sequence":"additional","affiliation":[{"name":"2 Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, Fukuoka, 812-8582, Japan"},{"name":"3 Institute for Advanced Study, Kyushu University, 6-10-1, Hakozaki, Higashi-Ku, Fukuoka, Fukuoka, 812-8581, Japan"},{"name":"\u2020 The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Kotera","sequence":"additional","affiliation":[{"name":"4 School of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-Ku, Tokyo, 152-8550, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,6,11]]},"reference":[{"key":"2023020112322729300_btw260-B1","doi-asserted-by":"crossref","first-page":"e1.","DOI":"10.1093\/pcp\/pcr165","article-title":"KNApSAcK family databases: integrated metabolite-plant species databases for multifaceted plant research","volume":"53","author":"Afendi","year":"2012","journal-title":"Plant Cell Physiol"},{"key":"2023020112322729300_btw260-B2","doi-asserted-by":"crossref","first-page":"10008.","DOI":"10.1038\/ncomms10008","article-title":"Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics","volume":"6","author":"Colin","year":"2015","journal-title":"Nat. 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