{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:09:31Z","timestamp":1762506571295},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":500,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Systems biology models can be used to test new hypotheses formulated on the basis of previous knowledge or new experimental data, contradictory with a previously existing model. New hypotheses often come in the shape of a set of possible regulatory mechanisms. This search is usually not limited to finding a single regulation link, but rather a combination of links subject to great uncertainty or no information about the kinetic parameters.<\/jats:p>\n               <jats:p>Results: In this work, we combine a logic-based formalism, to describe all the possible regulatory structures for a given dynamic model of a pathway, with mixed-integer dynamic optimization (MIDO). This framework aims to simultaneously identify the regulatory structure (represented by binary parameters) and the real-valued parameters that are consistent with the available experimental data, resulting in a logic-based differential equation model. The alternative to this would be to perform real-valued parameter estimation for each possible model structure, which is not tractable for models of the size presented in this work. The performance of the method presented here is illustrated with several case studies: a synthetic pathway problem of signaling regulation, a two-component signal transduction pathway in bacterial homeostasis, and a signaling network in liver cancer cells.<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <jats:p>Contact: \u00a0julio@iim.csic.es or saezrodriguez@ebi.ac.uk<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv314","type":"journal-article","created":{"date-parts":[[2015,5,23]],"date-time":"2015-05-23T00:50:24Z","timestamp":1432342224000},"page":"2999-3007","source":"Crossref","is-referenced-by-count":23,"title":["Reverse engineering of logic-based differential equation models using a mixed-integer dynamic optimization approach"],"prefix":"10.1093","volume":"31","author":[{"given":"David","family":"Henriques","sequence":"first","affiliation":[{"name":"1 Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C\/Eduardo Cabello 6, 36208 Vigo, Spain, 2Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and 3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK"},{"name":"1 Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C\/Eduardo Cabello 6, 36208 Vigo, Spain, 2Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and 3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK"}]},{"given":"Miguel","family":"Rocha","sequence":"additional","affiliation":[{"name":"1 Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C\/Eduardo Cabello 6, 36208 Vigo, Spain, 2Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and 3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK"}]},{"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[{"name":"1 Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C\/Eduardo Cabello 6, 36208 Vigo, Spain, 2Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and 3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK"}]},{"given":"Julio R.","family":"Banga","sequence":"additional","affiliation":[{"name":"1 Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C\/Eduardo Cabello 6, 36208 Vigo, Spain, 2Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal and 3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK"}]}],"member":"286","published-online":{"date-parts":[[2015,5,21]]},"reference":[{"key":"2023020202232174700_btv314-B1","first-page":"17","article-title":"Identification of genetic networks from a small number of gene expression patterns under the Boolean network model","volume":"5","author":"Akutsu","year":"1999","journal-title":"Pac. 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