{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:41:00Z","timestamp":1772775660505,"version":"3.50.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T00:00:00Z","timestamp":1566518400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Horizon 2020 Program of the European Commission","award":["643063"],"award-info":[{"award-number":["643063"]}]},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"crossref","award":["024.002.003"],"award-info":[{"award-number":["024.002.003"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-17-CE20-0031"],"award-info":[{"award-number":["ANR-17-CE20-0031"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2015\/13430-9"],"award-info":[{"award-number":["2015\/13430-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2017\/05986-2"],"award-info":[{"award-number":["2017\/05986-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Analysis of differential expression of genes is often performed to understand how the metabolic activity of an organism is impacted by a perturbation. However, because the system of metabolic regulation is complex and all changes are not directly reflected in the expression levels, interpreting these data can be difficult.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this work, we present a new algorithm and computational tool that uses a genome-scale metabolic reconstruction to infer metabolic changes from differential expression data. Using the framework of constraint-based analysis, our method produces a qualitative hypothesis of a change in metabolic activity. In other words, each reaction of the network is inferred to have increased, decreased, or remained unchanged in flux. In contrast to similar previous approaches, our method does not require a biological objective function and does not assign on\/off activity states to genes. An implementation is provided and it is available online. We apply the method to three published datasets to show that it successfully accomplishes its two main goals: confirming or rejecting metabolic changes suggested by differentially expressed genes based on how well they fit in as parts of a coordinated metabolic change, as well as inferring changes in reactions whose genes did not undergo differential expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>github.com\/htpusa\/moomin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz584","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T19:24:47Z","timestamp":1566242687000},"page":"514-523","source":"Crossref","is-referenced-by-count":21,"title":["MOOMIN \u2013 Mathematical explOration of \u2019Omics data on a MetabolIc Network"],"prefix":"10.1093","volume":"36","author":[{"given":"Taneli","family":"Pusa","sequence":"first","affiliation":[{"name":"INRIA Grenoble Rh\u00f4ne-Alpes , Montbonnot-Saint-Martin 38334, France"},{"name":"Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive , UMR 5558, CNRS, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Villeurbanne 69622, France"},{"name":"Department of Computer, Automatic and Management Engineering , Sapienza University of Rome, Rome 00185, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-9991","authenticated-orcid":false,"given":"Mariana Galv\u00e3o","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive , UMR 5558, CNRS, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Villeurbanne 69622, France"},{"name":"Univ Lyon, INSA-Lyon, INRA , BF2i, UMR0203, F-69621, Villeurbanne 69622, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Andrade","sequence":"additional","affiliation":[{"name":"INRIA Grenoble Rh\u00f4ne-Alpes , Montbonnot-Saint-Martin 38334, France"},{"name":"Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive , UMR 5558, CNRS, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Villeurbanne 69622, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Mary","sequence":"additional","affiliation":[{"name":"INRIA Grenoble Rh\u00f4ne-Alpes , Montbonnot-Saint-Martin 38334, France"},{"name":"Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive , UMR 5558, CNRS, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Villeurbanne 69622, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Marchetti-Spaccamela","sequence":"additional","affiliation":[{"name":"Department of Computer, Automatic and Management Engineering , Sapienza University of Rome, Rome 00185, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leen","family":"Stougie","sequence":"additional","affiliation":[{"name":"CWI , 1098XG Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-France","family":"Sagot","sequence":"additional","affiliation":[{"name":"INRIA Grenoble Rh\u00f4ne-Alpes , Montbonnot-Saint-Martin 38334, France"},{"name":"Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive , UMR 5558, CNRS, Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Villeurbanne 69622, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"2023013112082735800_btz584-B1","doi-asserted-by":"crossref","first-page":"e1002518.","DOI":"10.1371\/journal.pcbi.1002518","article-title":"Reconstruction of genome-scale active metabolic networks for 69 human cell types and 16 cancer types using INIT","volume":"8","author":"Agren","year":"2012","journal-title":"PLoS Comput. 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