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Multiomic characterization of disease progression in mice lacking dystrophin

Duchenne muscular dystrophy (DMD) is caused by genetic mutations leading to lack of dystrophin in skeletal muscle. A better understanding of how objective biomarkers for DMD vary across subjects and over time is needed to model disease progression and response to therapy more effectively, both in pr...

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Autores principales: Signorelli, Mirko, Tsonaka, Roula, Aartsma-Rus, Annemieke, Spitali, Pietro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065259/
https://www.ncbi.nlm.nih.gov/pubmed/37000843
http://dx.doi.org/10.1371/journal.pone.0283869
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author Signorelli, Mirko
Tsonaka, Roula
Aartsma-Rus, Annemieke
Spitali, Pietro
author_facet Signorelli, Mirko
Tsonaka, Roula
Aartsma-Rus, Annemieke
Spitali, Pietro
author_sort Signorelli, Mirko
collection PubMed
description Duchenne muscular dystrophy (DMD) is caused by genetic mutations leading to lack of dystrophin in skeletal muscle. A better understanding of how objective biomarkers for DMD vary across subjects and over time is needed to model disease progression and response to therapy more effectively, both in pre-clinical and clinical research. We present an in-depth characterization of disease progression in 3 murine models of DMD by multiomic analysis of longitudinal trajectories between 6 and 30 weeks of age. Integration of RNA-seq, mass spectrometry-based metabolomic and lipidomic data obtained in muscle and blood samples by Multi-Omics Factor Analysis (MOFA) led to the identification of 8 latent factors that explained 78.8% of the variance in the multiomic dataset. Latent factors could discriminate dystrophic and healthy mice, as well as different time-points. MOFA enabled to connect the gene expression signature in dystrophic muscles, characterized by pro-fibrotic and energy metabolism alterations, to inflammation and lipid signatures in blood. Our results show that omic observations in blood can be directly related to skeletal muscle pathology in dystrophic muscle.
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spelling pubmed-100652592023-04-01 Multiomic characterization of disease progression in mice lacking dystrophin Signorelli, Mirko Tsonaka, Roula Aartsma-Rus, Annemieke Spitali, Pietro PLoS One Research Article Duchenne muscular dystrophy (DMD) is caused by genetic mutations leading to lack of dystrophin in skeletal muscle. A better understanding of how objective biomarkers for DMD vary across subjects and over time is needed to model disease progression and response to therapy more effectively, both in pre-clinical and clinical research. We present an in-depth characterization of disease progression in 3 murine models of DMD by multiomic analysis of longitudinal trajectories between 6 and 30 weeks of age. Integration of RNA-seq, mass spectrometry-based metabolomic and lipidomic data obtained in muscle and blood samples by Multi-Omics Factor Analysis (MOFA) led to the identification of 8 latent factors that explained 78.8% of the variance in the multiomic dataset. Latent factors could discriminate dystrophic and healthy mice, as well as different time-points. MOFA enabled to connect the gene expression signature in dystrophic muscles, characterized by pro-fibrotic and energy metabolism alterations, to inflammation and lipid signatures in blood. Our results show that omic observations in blood can be directly related to skeletal muscle pathology in dystrophic muscle. Public Library of Science 2023-03-31 /pmc/articles/PMC10065259/ /pubmed/37000843 http://dx.doi.org/10.1371/journal.pone.0283869 Text en © 2023 Signorelli et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Signorelli, Mirko
Tsonaka, Roula
Aartsma-Rus, Annemieke
Spitali, Pietro
Multiomic characterization of disease progression in mice lacking dystrophin
title Multiomic characterization of disease progression in mice lacking dystrophin
title_full Multiomic characterization of disease progression in mice lacking dystrophin
title_fullStr Multiomic characterization of disease progression in mice lacking dystrophin
title_full_unstemmed Multiomic characterization of disease progression in mice lacking dystrophin
title_short Multiomic characterization of disease progression in mice lacking dystrophin
title_sort multiomic characterization of disease progression in mice lacking dystrophin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065259/
https://www.ncbi.nlm.nih.gov/pubmed/37000843
http://dx.doi.org/10.1371/journal.pone.0283869
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