A cross-study transcriptional analysis of Parkinson's disease

Sutherland, Greg T., Matigian, Nicholas A., Chalk, Alistair M., Anderson, Matthew J., Silburn, Peter A., Mackay-Sim, Alan, Wells, Christine A. and Mellick, George D. (2009) A cross-study transcriptional analysis of Parkinson's disease. PLoS One, 4 3: e4944-1-e4944-8. doi:10.1371/journal.pone.0004955

Author Sutherland, Greg T.
Matigian, Nicholas A.
Chalk, Alistair M.
Anderson, Matthew J.
Silburn, Peter A.
Mackay-Sim, Alan
Wells, Christine A.
Mellick, George D.
Title A cross-study transcriptional analysis of Parkinson's disease
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2009-03-23
Sub-type Article (original research)
DOI 10.1371/journal.pone.0004955
Open Access Status DOI
Volume 4
Issue 3
Start page e4944-1
End page e4944-8
Total pages 8
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract The study of Parkinson's disease (PD), like other complex neurodegenerative disorders, is limited by access to brain tissue from patients with a confirmed diagnosis. Alternatively the study of peripheral tissues may offer some insight into the molecular basis of disease susceptibility and progression, but this approach still relies on brain tissue to benchmark relevant molecular changes against. Several studies have reported whole-genome expression profiling in post-mortem brain but reported concordance between these analyses is lacking. Here we apply a standardised pathway analysis to seven independent case-control studies, and demonstrate increased concordance between data sets. Moreover data convergence increased when the analysis was limited to the five substantia nigra (SN) data sets; this highlighted the down regulation of dopamine receptor signaling and insulin-like growth factor 1 (IGF1) signaling pathways. We also show that case-control comparisons of affected post mortem brain tissue are more likely to reflect terminal cytoarchitectural differences rather than primary pathogenic mechanisms. The implementation of a correction factor for dopaminergic neuronal loss predictably resulted in the loss of significance of the dopamine signaling pathway while axon guidance pathways increased in significance. Interestingly the IGF1 signaling pathway was also over-represented when data from non-SN areas, unaffected or only terminally affected in PD, were considered. Our findings suggest that there is greater concordance in PD whole-genome expression profiling when standardised pathway membership rather than ranked gene list is used for comparison.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 50 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 09 Mar 2011, 14:35:01 EST