An integrative network approach for longitudinal stratification in Parkinson's disease

PLoS Comput Biol. 2025 Mar 28;21(3):e1012857. doi: 10.1371/journal.pcbi.1012857. eCollection 2025.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms resulting from the loss of dopamine-producing neurons in the brain. Currently, there is no cure for the disease which is in part due to the heterogeneity in patient symptoms, trajectories and manifestations. There is a known genetic component of PD and genomic datasets have helped to uncover some aspects of the disease. Understanding the longitudinal variability of PD is essential as it has been theorised that there are different triggers and underlying disease mechanisms at different points during disease progression. In this paper, we perform longitudinal and cross-sectional experiments to identify which data modalities or combinations of modalities are informative at different time points. We use clinical, genomic, and proteomic data from the Parkinson's Progression Markers Initiative. We validate the importance of flexible data integration by highlighting the varying combinations of data modalities for optimal stratification at different disease stages in idiopathic PD. We show there is a shared signal in the DNAm signatures of participants with a mutation in a causal gene of PD and participants with idiopathic PD. We also show that integration of SNPs and DNAm data modalities has potential for use as an early diagnostic tool for individuals with a genetic cause of PD.

MeSH terms

  • Biomarkers
  • Computational Biology
  • Cross-Sectional Studies
  • Disease Progression
  • Genomics
  • Humans
  • Longitudinal Studies
  • Mutation
  • Parkinson Disease* / diagnosis
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Polymorphism, Single Nucleotide
  • Proteomics

Substances

  • Biomarkers