Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy

PLoS One. 2018 Mar 12;13(3):e0194225. doi: 10.1371/journal.pone.0194225. eCollection 2018.

Abstract

Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism*
  • Protein Interaction Mapping*
  • Protein Interaction Maps*
  • Proteome*
  • Proteomics* / methods
  • Signal Transduction
  • Workflow

Substances

  • Proteome

Grants and funding

This project was partially funded by Provincia Autonoma di Trento - Zoomer project. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.