Systematic analysis of microarray datasets to identify Parkinson's disease‑associated pathways and genes

Mol Med Rep. 2017 Mar;15(3):1252-1262. doi: 10.3892/mmr.2017.6124. Epub 2017 Jan 16.

Abstract

In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co‑expression networks and clinical information was adopted, using weighted gene co‑expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD. Functional enrichment analysis of commonly disturbed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Co‑pathway relationships were identified with Pearson's correlation coefficient tests and a hypergeometric distribution‑based test. Common genes in pathway pairs were selected out and regarded as risk genes. A total of 17 microarray datasets from 7 platforms were retained for further analysis. Five gene coexpression modules were identified, containing 9,745, 736, 233, 101 and 93 genes, respectively. One module was significantly correlated with PD samples and thus the 736 genes it contained were considered to be candidate PD‑associated genes. Functional enrichment analysis demonstrated that these genes were implicated in oxidative phosphorylation and PD. A total of 44 pathway pairs and 52 risk genes were revealed, and a risk gene pathway relationship network was constructed. Eight modules were identified and were revealed to be associated with PD, cancers and metabolism. A number of disturbed pathways and risk genes were unveiled in PD, and these findings may help advance understanding of PD pathogenesis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Computational Biology / methods
  • Datasets as Topic
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Gene Ontology
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Signal Transduction*
  • Transcriptome