{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:29:55Z","timestamp":1777660195228,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister of Economy and Competitiveness of Spain","award":["PID2022-143298OB-I00"],"award-info":[{"award-number":["PID2022-143298OB-I00"]}]},{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["PIBA_2020_01_0055"],"award-info":[{"award-number":["PIBA_2020_01_0055"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Genome-scale metabolic models lack explicit regulatory mechanisms, limiting their predictive accuracy for genetic interventions. Current methods for computing genetic Minimal Cut Sets either ignore regulatory networks entirely or use simplified acyclic representations that cannot capture regulatory feedback loops, ubiquitous features critical in cellular modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We developed gMISpy, a Python package that that enables efficient computation of genetic Minimal Intervention Sets (gMISs) in integrated genome-scale metabolic and regulatory networks. gMISpy incorporates cyclic regulatory logic into our previous computational framework using layered Boolean networks and BoNesis framework, resulting in a more accurate modeling of how regulatory interactions affect metabolic genes. Benchmarking across four different regulatory networks with Human-GEM showed consistent improvements in prediction accuracy, with Matthews correlation coefficient gains ranging from 2.50% to 14.42%. Validation against cancer data from DepMap and Project Score confirmed that cyclic integration reduces false positives and better captures biological vulnerabilities compared to acyclic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>https:\/\/github.com\/PlanesLab\/cyclic-gMISpy<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag180","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:56:39Z","timestamp":1775649399000},"source":"Crossref","is-referenced-by-count":0,"title":["gMISpy: integration of complex regulatory networks and genome scale metabolic models"],"prefix":"10.1093","volume":"42","author":[{"given":"Carlos J","family":"Rodriguez-Flores","sequence":"first","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , San Sebasti\u00e1n 20018,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4324-3371","authenticated-orcid":false,"given":"Naroa","family":"Barrena","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , San Sebasti\u00e1n 20018,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-2027","authenticated-orcid":false,"given":"Lo\u00efc","family":"Paulev\u00e9","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS, Bordeaux INP, LaBRI, UMR 5800 , Talence F-33400,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-3105","authenticated-orcid":false,"given":"Francisco J","family":"Planes","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , San Sebasti\u00e1n 20018,","place":["Spain"]},{"name":"Biomedical Engineering Center, University of Navarra, Campus Universitario , Pamplona, Navarra 31009,","place":["Spain"]},{"name":"Instituto de Ciencia de los Datos e Inteligencia Artificial (DATAI), University of Navarra, Campus Universitario , Pamplona 31080,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"2026042903213295500_btag180-B1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41467-017-00555-y","article-title":"An in-silico approach to predict 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