Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes
Abstract Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders;...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45099-0 |
| _version_ | 1797273916644786176 |
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| author | Iker Núñez-Carpintero Maria Rigau Mattia Bosio Emily O’Connor Sally Spendiff Yoshiteru Azuma Ana Topf Rachel Thompson Peter A. C. ’t Hoen Teodora Chamova Ivailo Tournev Velina Guergueltcheva Steven Laurie Sergi Beltran Salvador Capella-Gutiérrez Davide Cirillo Hanns Lochmüller Alfonso Valencia |
| author_facet | Iker Núñez-Carpintero Maria Rigau Mattia Bosio Emily O’Connor Sally Spendiff Yoshiteru Azuma Ana Topf Rachel Thompson Peter A. C. ’t Hoen Teodora Chamova Ivailo Tournev Velina Guergueltcheva Steven Laurie Sergi Beltran Salvador Capella-Gutiérrez Davide Cirillo Hanns Lochmüller Alfonso Valencia |
| author_sort | Iker Núñez-Carpintero |
| collection | DOAJ |
| description | Abstract Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases. |
| first_indexed | 2024-03-07T14:50:58Z |
| format | Article |
| id | doaj.art-da340b3b30af42679f99a2df69ba8241 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:50:58Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-da340b3b30af42679f99a2df69ba82412024-03-05T19:42:56ZengNature PortfolioNature Communications2041-17232024-02-0115111510.1038/s41467-024-45099-0Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic SyndromesIker Núñez-Carpintero0Maria Rigau1Mattia Bosio2Emily O’Connor3Sally Spendiff4Yoshiteru Azuma5Ana Topf6Rachel Thompson7Peter A. C. ’t Hoen8Teodora Chamova9Ivailo Tournev10Velina Guergueltcheva11Steven Laurie12Sergi Beltran13Salvador Capella-Gutiérrez14Davide Cirillo15Hanns Lochmüller16Alfonso Valencia17Barcelona Supercomputing Center (BSC)Barcelona Supercomputing Center (BSC)Barcelona Supercomputing Center (BSC)Children’s Hospital of Eastern Ontario Research InstituteChildren’s Hospital of Eastern Ontario Research InstituteDepartment of Human Genetics, Yokohama City University Graduate School of MedicineJohn Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle UniversityChildren’s Hospital of Eastern Ontario Research InstituteCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical centerDepartment of Neurology, Expert Centre for Hereditary Neurologic and Metabolic Disorders, Alexandrovska University Hospital, Medical University-SofiaDepartment of Neurology, Expert Centre for Hereditary Neurologic and Metabolic Disorders, Alexandrovska University Hospital, Medical University-SofiaClinic of Neurology, University Hospital Sofiamed, Sofia University St. Kliment OhridskiCentro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST)Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST)Barcelona Supercomputing Center (BSC)Barcelona Supercomputing Center (BSC)Children’s Hospital of Eastern Ontario Research InstituteBarcelona Supercomputing Center (BSC)Abstract Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases.https://doi.org/10.1038/s41467-024-45099-0 |
| spellingShingle | Iker Núñez-Carpintero Maria Rigau Mattia Bosio Emily O’Connor Sally Spendiff Yoshiteru Azuma Ana Topf Rachel Thompson Peter A. C. ’t Hoen Teodora Chamova Ivailo Tournev Velina Guergueltcheva Steven Laurie Sergi Beltran Salvador Capella-Gutiérrez Davide Cirillo Hanns Lochmüller Alfonso Valencia Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes Nature Communications |
| title | Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes |
| title_full | Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes |
| title_fullStr | Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes |
| title_full_unstemmed | Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes |
| title_short | Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes |
| title_sort | rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in congenital myasthenic syndromes |
| url | https://doi.org/10.1038/s41467-024-45099-0 |
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