ABSTRACT: mRNA-Seq expression and MS3 proteomics profiling of human post-mortem BA9 brain tissue for Parkinson Disease and neurologically normal individuals
Project description:Parkinson disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein (SNCA) and other proteins in aggregates termed âLewy Bodiesâ 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. After appropriate filters, proteomics identified 3,558 unique proteins and 283 of these (7.9%) were significantly different between PD and controls (q-value<0.05). RNA-sequencing identified 17,580 protein-coding genes and 1,095 of these (6.2%) were significantly different (FDR p-value<0.05), but only 166 of the FDR significant protein-coding genes (0.94%) were present among the 3,558 proteins characterized. Of these 166, eight genes (4.8%) were significant in both studies, with the same direction of effect. Functional enrichment analysis of the proteomics results strongly supports mitochondrial-related pathways, while comparable analysis of the RNA-sequencing results implicates protein folding pathways and metallothioneins. Ten of the implicated genes or proteins co-localized to GWAS loci. Evidence implicating SNCA was stronger in proteomics than in RNA-sequencing analyses. Notably, differentially expressed protein-coding genes were more likely to not be characterized in the proteomics analysis, which lessens the ability to compare across platforms. Combining multiple genome-wide platforms offers novel insights into the pathological processes responsible for this disease by identifying pathways implicated across methodologies. The study consists of mRNA-Seq (29 PD, 44 neurologically normal controls) and three-stage Mass Spectrometry Tandem Mass Tag Proteomics (12 PD, 12 neurologically normal controls) performed in post-mortem BA9 brain tissue. The proteomics samples are a subset of the RNA-Seq samples.
Project description:This data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain.
Project description:This data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain.
Project description:This data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain. This SuperSeries is composed of the SubSeries listed below.
Project description:This data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain. 1231 samples are analysed in total and these samples originate from 134 Caucasian individuals. From each individual, up to ten brain regions were sampled and analysed.
Project description:This data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain. 1231 samples are analysed in total and these samples originate from 134 Caucasian individuals. From each individual, up to ten brain regions were sampled and analysed.
Project description:miRNA-seq expression profiling of Huntington's Disease and neurologically normal human post-mortem prefrontal cortex (BA9) brain samples
Project description:Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum, frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite. Keywords: disease state analysis
Project description:Expression data generated from post-mortem human brain tissue originating from neurologically and neuropathologically control individuals
