2026-06-14T03:33:39Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/183152024-11-28T14:59:31Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Díaz-Santiago, Elena author Claros, M. Gonzalo author Yahyaoui, Raquel author de Diego-Otero, Yolanda author Calvo, Rocío author Hoenicka, Janet author Palau, Francesc author Ranea, Juan A. G. author Perkins, James R. authoraffiliation [Díaz-Santiago,E; Claros,MG; Ranea,JAG; Perkins,JR] Department of Molecular Biology and Biochemistry, Universidad de Málaga, Málaga, Spain. [Claros,MG; Ranea,JAG; Hoenicka,J; Palau,F; Ranea,JAG; Perkins,JR] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. [Claros,MG; Yahyaoui,R; de Diego-Otero,Y; Calvo,R; Ranea,JAG; Perkins,JR] Institute of Biomedical Research in Malaga (IBIMA), IBIMA-RARE, Málaga, Spain. [Claros,MG] Institute for Mediterranean and Subtropical Horticulture "La Mayora" (IHSM-UMA-CSIC), Málaga, Spain, [Yahyaoui,R; Calvo,R] Laboratory of Metabolopathies and Neonatal Screening, Málaga Regional University Hospital, Málaga, Spain. [Hoenicka,J; Palau,F] Sant Joan de Déu Hospital and Research Institute, Barcelona, Spain. [Palau,F] Hospital Clínic and University of Barcelona School of Medicine and Health Sciences, Barcelona, Spain. 2024-02-19T15:26:55Z 2024-02-19T15:26:55Z 2021-04-19 10.3389/fmolb.2021.635074 2296-889X Frontiers in Molecular Biosciences https://hdl.handle.net/10668/3667 34046427 http://hdl.handle.net/20.500.12105/18315 Neuromuscular disorders (NMDs) represent an important subset of rare diseases associated with elevated morbidity and mortality whose diagnosis can take years. Here we present a novel approach using systems biology to produce functionally-coherent phenotype clusters that provide insight into the cellular functions and phenotypic patterns underlying NMDs, using the Human Phenotype Ontology as a common framework. Gene and phenotype information was obtained for 424 NMDs in OMIM and 126 NMDs in Orphanet, and 335 and 216 phenotypes were identified as typical for NMDs, respectively. Elevated serum creatine kinase was the most specific to NMDs, in agreement with the clinical test of elevated serum creatinine kinase that is conducted on NMD patients. The approach to obtain co-occurring NMD phenotypes was validated based on co-mention in PubMed abstracts. A total of 231 (OMIM) and 150 (Orphanet) clusters of highly connected co-occurrent NMD phenotypes were obtained. In parallel, a tripartite network based on phenotypes, diseases and genes was used to associate NMD phenotypes with functions, an approach also validated by literature co-mention, with KEGG pathways showing proportionally higher overlap than Gene Ontology and Reactome. Phenotype-function pairs were crossed with the co-occurrent NMD phenotype clusters to obtain 40 (OMIM) and 72 (Orphanet) functionally coherent phenotype clusters. As expected, many of these overlapped with known diseases and confirmed existing knowledge. Other clusters revealed interesting new findings, indicating informative phenotypes for differential diagnosis, providing deeper knowledge of NMDs, and pointing towards specific cell dysfunction caused by pleiotropic genes. This work is an example of reproducible research that i) can help better understand NMDs and support their diagnosis by providing a new tool that exploits existing information to obtain novel clusters of functionally-related phenotypes, and ii) takes us another step towards personalised medicine for NMDs. eng Cluster Co-occurrence analysis Network analysis Neuromuscular disorders Phenotype Rare disease Fenotipo Enfermedades raras Decoding Neuromuscular Disorders Using Phenotypic Clusters Obtained From Co-Occurrence Networks research article