Multiomic characterization of disease progression in mice lacking dystrophin

PLoS One. 2023 Mar 31;18(3):e0283869. doi: 10.1371/journal.pone.0283869. eCollection 2023.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Dystrophin* / genetics
  • Dystrophin* / metabolism
  • Mice
  • Mice, Inbred mdx
  • Multiomics
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne* / pathology

Substances

  • Dystrophin

Grants and funding

PS: Duchenne Parent Project NL. Website: https://duchenne.nl/. Project number 16.006. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.