Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes
Year: 2024
Type: article
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.
Source: Nature Communications
Authors: 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
Institutions: Barcelona Supercomputing Center, Hammersmith Hospital, MRC London Institute of Medical Sciences, Imperial College London, University of Ottawa, Children's Hospital of Eastern Ontario, uOttawa Brain and Mind Research Institute, Aichi Medical University, Yokohama City University, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle University, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Alexandrovska Hospital, Medical University of Sofia, New Bulgarian University, Sofia University "St. Kliment Ohridski", Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Centro Nacional de Análisis Genómico, Universitat Pompeu Fabra, Universitat de Barcelona, University of Freiburg, Ottawa Hospital, University Medical Center Freiburg, Institució Catalana de Recerca i Estudis Avançats
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: G1443089283, RD-CONNECT: An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research, Robust Learning and Reasoning for Complex Event Forecasting, G4466902010, G4785284928, G5097141464, individualizedPaediatricCure: Cloud-based virtual-patient models for precision paediatric oncology, G675428038, G7076316076, Integrated European –omics research project for diagnosis and therapy in rare neuromuscular and neurodegenerative diseases
OpenAlex ID: W4392238947