{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:22:43Z","timestamp":1773368563552,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["FI17\/00297"],"award-info":[{"award-number":["FI17\/00297"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Economy and Competitiveness of Spain","award":["BIO2013-48933"],"award-info":[{"award-number":["BIO2013-48933"]}]},{"name":"Ministry of Economy and Competitiveness of Spain","award":["BIO2016-77998-R"],"award-info":[{"award-number":["BIO2016-77998-R"]}]},{"name":"ELKARTEK Programme of the Basque Government","award":["KK-2016\/00026"],"award-info":[{"award-number":["KK-2016\/00026"]}]},{"name":"ELKARTEK Programme of the Basque Government","award":["KK-2017\/00084"],"award-info":[{"award-number":["KK-2017\/00084"]}]},{"name":"Fundaci\u00f3n Vasca de Innovaci\u00f3n e Investigaci\u00f3n Sanitarias, BIOEF","award":["BIO15\/CA\/052"],"award-info":[{"award-number":["BIO15\/CA\/052"]}]},{"name":"Basque Department of Health","award":["2016111109"],"award-info":[{"award-number":["2016111109"]}]},{"name":"Basque Department of Industry, Tourism and Trade","award":["IT1106-16"],"award-info":[{"award-number":["IT1106-16"]}]},{"DOI":"10.13039\/100007406","name":"BBVA foundation","doi-asserted-by":"publisher","award":["SAF2016-79381-R"],"award-info":[{"award-number":["SAF2016-79381-R"]}],"id":[{"id":"10.13039\/100007406","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Severo Ochoa Excellence Accreditation","award":["SEV-2016-0644"],"award-info":[{"award-number":["SEV-2016-0644"]}]},{"name":"Excellence Networks","award":["SAF2016-81975-REDT"],"award-info":[{"award-number":["SAF2016-81975-REDT"]}]},{"name":"European Training Networks Project","award":["H2020-MSCA-ITN-308 2016 721532"],"award-info":[{"award-number":["H2020-MSCA-ITN-308 2016 721532"]}]},{"name":"European Training Networks Project","award":["IDEAS175CARR; GCTRA18006CARR"],"award-info":[{"award-number":["IDEAS175CARR; GCTRA18006CARR"]}]},{"name":"the European Research Council","award":["336343, PoC 754627"],"award-info":[{"award-number":["336343, PoC 754627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The development of computational tools exploiting -omics data and high-quality genome-scale metabolic networks for the identification of novel drug targets is a relevant topic in Systems Medicine. Metabolic Transformation Algorithm (MTA) is one of these tools, which aims to identify targets that transform a disease metabolic state back into a healthy state, with potential application in any disease where a clear metabolic alteration is observed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we present a robust extension to MTA (rMTA), which additionally incorporates a worst-case scenario analysis and minimization of metabolic adjustment to evaluate the beneficial effect of gene knockouts. We show that rMTA complements MTA in the different datasets analyzed (gene knockout perturbations in different organisms, Alzheimer\u2019s disease and prostate cancer), bringing a more accurate tool for predicting therapeutic targets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>rMTA is freely available on The Cobra Toolbox: https:\/\/opencobra.github.io\/cobratoolbox\/latest\/.<\/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\/btz231","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T22:22:37Z","timestamp":1553725357000},"page":"4350-4355","source":"Crossref","is-referenced-by-count":21,"title":["rMTA: robust metabolic transformation analysis"],"prefix":"10.1093","volume":"35","author":[{"given":"Luis V","family":"Valc\u00e1rcel","sequence":"first","affiliation":[{"name":"Tecnun, University of Navarra , San Sebasti\u00e1n 20018, Spain"},{"name":"Area de Hemato-Oncolog\u00eda, IDISNA, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), University of Navarra , Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Faculty of Medicine, Joint Research Centre for Computational Biomedicine, RWTH Aachen University , Aachen D-52074, Germany"}]},{"given":"Ver\u00f3nica","family":"Torrano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Faculty of Medicine, Joint Research Centre for Computational Biomedicine, RWTH Aachen University , Aachen D-52074, Germany"},{"name":"CIC bioGUNE, Bizkaia Technology Park , Derio, Spain"}]},{"given":"Luis","family":"Tobalina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Joint Research Centre for Computational Biomedicine, RWTH Aachen University , Aachen D-52074, Germany"}]},{"given":"Arkaitz","family":"Carracedo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Faculty of Medicine, Joint Research Centre for Computational Biomedicine, RWTH Aachen University , Aachen D-52074, Germany"},{"name":"CIC bioGUNE, Bizkaia Technology Park , Derio, Spain"},{"name":"Ikerbasque, Basque foundation for science , Bilbao, Spain"},{"name":"Biochemistry and Molecular Biology Department, University of the Basque Country (UPV\/EHU) , Bilbao E-48080, Spain"}]},{"given":"Francisco J","family":"Planes","sequence":"additional","affiliation":[{"name":"Tecnun, University of Navarra , San Sebasti\u00e1n 20018, Spain"}]}],"member":"286","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2023062712531012700_btz231-B1","doi-asserted-by":"crossref","first-page":"459.","DOI":"10.1038\/s41467-017-00555-y","article-title":"An in-silico approach to predict and exploit synthetic lethality in cancer metabolism","volume":"8","author":"Apaolaza","year":"2017","journal-title":"Nat. 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