{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T16:25:42Z","timestamp":1757780742667},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,10,6]],"date-time":"2016-10-06T00:00:00Z","timestamp":1475712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Skeletal muscle dysfunction is a systemic effect in one-third of patients with chronic obstructive pulmonary disease (COPD), characterized by high reactive-oxygen-species (ROS) production and abnormal endurance training-induced adaptive changes. However, the role of ROS in COPD remains unclear, not least because of the lack of appropriate tools to study multifactorial diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We describe a discrete model-driven method combining mechanistic and probabilistic approaches to decipher the role of ROS on the activity state of skeletal muscle regulatory network, assessed before and after an 8-week endurance training program in COPD patients and healthy subjects. In COPD, our computational analysis indicates abnormal training-induced regulatory responses leading to defective tissue remodeling and abnormal energy metabolism. Moreover, we identified tnf, insr, inha and myc as key regulators of abnormal training-induced adaptations in COPD. The tnf-insr pair was identified as a promising target for therapeutic interventions. Our work sheds new light on skeletal muscle dysfunction in COPD, opening new avenues for cost-effective therapies. It overcomes limitations of previous computational approaches showing high potential for the study of other multi-factorial diseases such as diabetes or cancer.<\/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\/btw566","type":"journal-article","created":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T03:06:21Z","timestamp":1475291181000},"page":"95-103","source":"Crossref","is-referenced-by-count":11,"title":["Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach"],"prefix":"10.1093","volume":"33","author":[{"given":"Igor","family":"Mar\u00edn de Mas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, Institute of Biomedicine of University of Barcelona (IBUB) and IDIBAPS, Diagonal 645, Barcelona, Spain"},{"name":"Institut d\u2019 Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Temesv\u00e1ri krt. 62, Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Fanchon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes-CNRS, TIMC-IMAG UMR 5525, Facult\u00e9 de M\u00e9decine, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Papp","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Temesv\u00e1ri krt. 62, Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Kalko","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Cl\u00ednic, University de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Roca","sequence":"additional","affiliation":[{"name":"Institut d\u2019 Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"Department of Pulmonary Medicine, Hospital Cl\u00ednic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Cascante","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, Institute of Biomedicine of University of Barcelona (IBUB) and IDIBAPS, Diagonal 645, Barcelona, Spain"},{"name":"Institut d\u2019 Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,10,6]]},"reference":[{"key":"2023020204313728000_btw566-B1","doi-asserted-by":"crossref","first-page":"D191","DOI":"10.1093\/nar\/gkt1140","article-title":"Activities at the Universal Protein Resource (UniProt)","volume":"42","author":"Apweiler","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023020204313728000_btw566-B2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrg1272","article-title":"Network biology: understanding the cells' functional organization","volume":"5","author":"Barabasi","year":"2004","journal-title":"Nat. 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