Integrative analyses of proteomics and RNA transcriptomics implicate mitochondrial processes, protein folding pathways and GWAS loci in Parkinson disease

BMC Medical Genomics
Alexandra DumitriuJeanne C Latourelle

Abstract

Parkinson disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein (SNCA) and other proteins in aggregates termed "Lewy Bodies" within neurons. PD has both genetic and environmental risk factors, and while processes leading to aberrant protein aggregation are unknown, past work points to abnormal levels of SNCA and other proteins. Although several genome-wide studies have been performed for PD, these have focused on DNA sequence variants by genome-wide association studies (GWAS) and on RNA levels (microarray transcriptomics), while genome-wide proteomics analysis has been lacking. This study employed two state-of-the-art technologies, three-stage Mass Spectrometry Tandem Mass Tag Proteomics (12 PD, 12 controls) and RNA-sequencing transcriptomics (29 PD, 44 controls), evaluated in the context of PD GWAS implicated loci and microarray transcriptomics (19 PD, 24 controls). The technologies applied for this study were performed in a set of overlapping prefrontal cortex (Brodmann area 9) samples obtained from PD patients and sex and age similar neurologically healthy controls. After appropriate filters, proteomics robustly identified 3558 unique proteins, with 283 of these (7.9 %) significantl...Continue Reading

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Datasets Mentioned

BETA
GSE68719
E-MTAB-812

Methods Mentioned

BETA
RNA-Seq
genotyping
PCR
protein folding

Software Mentioned

sva R
ipython notebook
RSeQC
pandas
matplotlib
R
custom R scripts
geneBody
Illumina Assessment of Sequence and Variation ( CASAVA )
TopHat

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