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Ciencia, Innovaci\u00f3n y Universidades","award":["ACCI-02-770"],"award-info":[{"award-number":["ACCI-02-770"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["101080580"],"award-info":[{"award-number":["101080580"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuromuscular diseases (NMDs) like Duchenne muscular dystrophy (DMD), limb\u2013girdle muscular dystrophy (LGMD), and amyotrophic lateral sclerosis (ALS) are rare, progressive disorders with complex molecular mechanisms. Traditional transcriptomic analyses often struggle to capture systems-level dysregulation, especially given the small sample sizes typical of rare disease studies. Our differential expression analysis of eight public RNA-seq datasets from various cell types in DMD, LGMD, and ALS revealed not only disease-relevant pathways but also unexpected enrichments, such as renal development, suggesting systemic impacts beyond muscle tissue. To address limitations in capturing broader molecular mechanisms, we applied an integrative systems biology approach combining differential expression data, protein\u2013protein interaction (PPI) networks, and network embedding techniques. Comparative functional enrichment revealed shared pathways, including glycosaminoglycan binding in both DMD and FUS-related ALS, implicating extracellular matrix\u2013protein interactions in FUS mutation effects. Mapping DEGs onto the human PPI network and assessing their proximity to causal genes uncovered dysregulated non-coding RNAs, such as PAX8-AS1, SBF2-AS1, and NEAT1, potentially indicating common regulatory roles. We also found candidate genes within disease-proximal clusters, like HS3ST3A1, which may contribute to pathogenesis. Overall, this integrative approach reveals shared transcriptional programs and novel targets, advancing our understanding and potential treatment strategies for NMDs.<\/jats:p>","DOI":"10.3390\/ijms26199376","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:48:28Z","timestamp":1758804508000},"page":"9376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrative Transcriptomic and Network-Based Analysis of Neuromuscular Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-8348","authenticated-orcid":false,"given":"Federico","family":"Garc\u00eda-Criado","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9059-3782","authenticated-orcid":false,"given":"Lucia","family":"Hurtado-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C\/ Severo Ochoa, 35, Parque Tecnol\u00f3gico de Andaluc\u00eda (PTA), Campanillas, 29590 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-710X","authenticated-orcid":false,"given":"Elena","family":"Rojano","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C\/ Severo Ochoa, 35, Parque Tecnol\u00f3gico de Andaluc\u00eda (PTA), Campanillas, 29590 M\u00e1laga, Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-7779","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Esteban-Martos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9388-7465","authenticated-orcid":false,"given":"Jes\u00fas","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-1415","authenticated-orcid":false,"given":"Pedro","family":"Seoane","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Bulevar Louis Pasteur, 31, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C\/ Severo Ochoa, 35, Parque Tecnol\u00f3gico de Andaluc\u00eda (PTA), Campanillas, 29590 M\u00e1laga, Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER), Avda. 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Monforte de Lemos, 3-5, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"},{"name":"Instituto Nacional de Bioinform\u00e1tica (INB\/ELIXIR-ES), Instituto de Salud Carlos III (ISCIII), C\/ Sinesio Delgado, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s00018-024-05229-9","article-title":"Molecular mechanisms and therapeutic strategies for neuromuscular diseases","volume":"81","author":"Zambon","year":"2024","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/ppul.26159","article-title":"Year in review 2021: Neuromuscular diseases","volume":"58","author":"Kelchtermans","year":"2023","journal-title":"Pediatr. 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