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Lookup NU author(s): Dr Ana TopfORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.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.
Author(s): Nunez-Carpintero I, Rigau M, Bosio M, O'Connor E, Spendiff S, Azuma Y, Topf A, Thompson R, 't Hoen PAC, Chamova T, Tournev I, Guergueltcheva V, Laurie S, Beltran S, Capella-Gutierrez S, Cirillo D, Lochmuller H, Valencia A
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2024
Volume: 15
Issue: 1
Online publication date: 28/02/2024
Acceptance date: 15/01/2024
Date deposited: 11/03/2024
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-024-45099-0
DOI: 10.1038/s41467-024-45099-0
Data Access Statement: WGS metadata and variant data, and patient phenotypic descriptions have been deposited in the RD-Connect GPAP: https://platform.rd-connect.eu/#/. This data is available under controlled access for registered users of the GPAP. Details on access to GPAP can be found in: https://platform.rd-connect.eu/userregistration. [See remainder of Data availability statement at https://www.nature.com/articles/s41467-024-45099-0#data-availability https://www.nature.com/articles/s41467-024-45099-0#code-availability ]
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