{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:29:45Z","timestamp":1764653385624,"version":"3.46.0"},"reference-count":44,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"Association Francaise contre les Myopathies","doi-asserted-by":"publisher","award":["23933"],"award-info":[{"award-number":["23933"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["576154"],"award-info":[{"award-number":["576154"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ecole Inserm Pfizer Innovation","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Myologie","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"IdEx Unistra","award":["ANR-10-IDEX-0002"],"award-info":[{"award-number":["ANR-10-IDEX-0002"]}]},{"name":"SFRI-STRAT\u2019US","award":["ANR-20-SFRI-0012"],"award-info":[{"award-number":["ANR-20-SFRI-0012"]}]},{"name":"EUR IMCBio","award":["ANR-17-EURE-0023"],"award-info":[{"award-number":["ANR-17-EURE-0023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Centronuclear and myotubular myopathies (CNMs) are rare, inherited muscle disorders characterized by muscle atrophy, weakness, and altered muscle fiber structure, primarily caused by mutations in MTM1, DNM2, or BIN1. The molecular mechanisms driving CNM are only partially understood, and no curative therapies are available. To elucidate molecular pathways involved in CNMs, we present an integrative multi-omics analysis across several CNM mouse models untreated or treated with pre-clinical strategies, combining transcriptomic, proteomic, and metabolomic datasets with curated interaction, metabolic, tissue, and phenotype knowledge using network-based approaches. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules commonly altered in three CNM genetic forms. Modules correlated with improved muscle function were enriched for processes such as muscle contraction, RNA metabolism, and oxidative phosphorylation, whereas modules linked to disease severity were enriched for immune response, innervation, vascularization, and fatty acid oxidation. We further integrated transcriptomic, proteomic, and metabolomic data from the Mtm1\u2212\/y mouse model with public knowledge bases into a multilayer network, and explored it using a random walk with restart approach. These analyses highlighted metabolites closely connected to CNM phenotypes, some of which may represent candidates for nutritional or pharmacological modulation. Our findings illustrate how integrative multi-omics and network analyses reveal both pathogenic and protective pathways in CNM and provide a foundation for identifying novel therapeutic opportunities.<\/jats:p>","DOI":"10.3390\/ijms262311572","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi-Omics and Network Analyses Reveal Pathogenic and Protective Pathways in Centronuclear Myopathies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-1951","authenticated-orcid":false,"given":"Alix","family":"Simon","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM UMRS 1258, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Gineste","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM UMRS 1258, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Reiss","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM UMRS 1258, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-3478","authenticated-orcid":false,"given":"Julie D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Complex Systems and Translational Bioinformatics (CSTB), ICube Laboratory\u2014CNRS, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg (FMTS), Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8256-5862","authenticated-orcid":false,"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM UMRS 1258, Universit\u00e9 de Strasbourg, 67404 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Oca, R., Cowling, B.S., and Laporte, J. 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