Genome-wide epigenetic analysis of Japanese immigrant plantation workers with Parkinson’s Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151355 | GEO | 2020/05/29
REPOSITORIES: GEO
Similar Datasets
Project description:The given data set is the first deep sequencing transcriptome-wide data set of human Parkinson's disease (PD) patients RNA. The data set was produced from blood leukocytes of PD patients, from the same patients following deep brain stimulation (DBS), and from matched healthy control volunteers. Post-DBS samples were taken from the patients while being on electrical stimulation (ON-Stim), and following one hour off of electrical stimulation (OFF-Stim state). We have previously shown that gene expression changes, and in particular, alternative splicing changes, are observed in blood leukocytes and may contribute to PD and being subjected to regulation following DBS. Here, SOLiD RNA-Seq was applied to study the transcriptome of PD patients. Exon- and junction-level analyses revealed deep insight into both differential expression and alternative splicing regulation in PD blood leukocytes prior to and following DBS both on and off electrical stimulation. This transcriptome genome-wide data obtained through high-throughput sequencing of RNA produced from human Parkinson's disease (PD) patients blood leukocytes prior to treatment and following deep brain stimulation (DBS) neurosurgical treatment may yield insights into the molecular mechanisms that underlie the pathogenesis of PD and treatment efficacy. It may further enable the development of future diagnostics and therapeutics for PD. Blood leukocyte RNA was analyzed from 3 healthy control volunteers, and from 3 PD patients pre-DBS, ON-Stim, and OFF-Stim.
2014-07-16 | E-GEOD-42608 | biostudies-arrayexpress
Project description:The ability to use blood to predict the outcomes of Parkinson’s disease (PD), including disease progression and development of cognitive and motor complications, would be of enormous clinical value. We undertook deep RNA sequencing from the caudate and putamen of postmortem PD (n=35) and control (n=40) striatum, and compared molecular profiles with clinical features, and samples obtained from antemortem peripheral blood from an independent cohort. Cognitive and motor complications of PD were associated with molecular changes in the caudate (e.g., stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset PD were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence) respectively. Molecular signatures in the postmortem PD brain were also evident in antemortem peripheral blood, and correlated with clinical disease features. Together, these findings identify molecular signatures in PD patients' brain and blood of potential pathophysiologic and prognostic importance
2023-07-05 | PXD042154 | Pride
Project description:Patients with Alzheimer’s disease (AD) and Parkinson disease (PD) often have overlap in brain neuropathology and clinical presentation suggesting that these two diseases share common underlying mechanisms. Currently, the molecular events linking AD and PD are incompletely understood. Utilizing 10-plex Tandem Mass Tag (TMT) assays and MultiNotch MS3 mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as healthy controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11,840 protein groups representing 10,230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra-batch and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of protein signatures and neuro-centric signaling pathways that are common or distinct in AD and PD.
2018-02-07 | PXD007160 | Pride
Project description:Cytosine DNA methylation is considered to be a stable epigenetic mark, but active demethylation has been observed in both plants and animals. In Arabidopsis thaliana, DNA glycosylases of the DEMETER (DME) family remove methylcytosines from DNA. Demethylation by DME is necessary for genomic imprinting and demethylation by a related protein, REPRESSOR OF SILENCING1, which prevents gene silencing in a transgenic background. However, the extent and function of demethylation by DEMETER-LIKE (DML) proteins in WT plants is not known. Using genome-tiling microarrays, we mapped DNA methylation in mutant and WT plants and identified 179 loci actively demethylated by DML enzymes. Mutations in DML genes lead to locus-specific DNA hypermethylation. Reintroducing WT DML genes restores most loci to the normal pattern of methylation, although at some loci, hypermethylated epialleles persist. Of loci demethylated by DML enzymes, >80% are near or overlap genes. Genic demethylation by DML enzymes primarily occurs at the 5' and 3' ends, a pattern opposite to the overall distribution of WT DNA methylation. Our results show that demethylation by DML DNA glycosylases edits the patterns of DNA methylation within the Arabidopsis genome to protect genes from potentially deleterious methylation. Keywords: whole genome profiling, DNA methylation, demethylase
2007-04-02 | GSE7336 | GEO
Project description:Importance. Biological markers of Parkinson’s disease are essential for achieving disease modification. Objective. To determine the association of SNCA blood transcript levels with prevalence of Parkinson’s disease. Background. The SNCA locus is preferentially transcribed in neurons and blood cells. Non-coding genetic variants and neuronal aggregates of α-synuclein protein associate this locus with sporadic Parkinson’s disease and suggest a potential role for abnormal SNCA transcription in the disease mechanism. Here we investigated variation in intracellular SNCA gene expression and SNCA transcript isoform abundance in circulating blood cells of cases with PD and controls in a network of biobanks that represent regional, national, and international populations. Design, Setting, Participants. Three cross-sectional, case-control studies nested in observational biomarker studies. 222 cases with early-stage clinical PD and 183 controls were enrolled from 2005 to 2010 in the Harvard Biomarker Study (HBS) at two Harvard-affiliated tertiary care centers. 76 cases with dopamine transporter imaging (DAT)-confirmed PD and 42 controls were enrolled between August 2007 and December 2008 in the Blood α-Synuclein, Gene Expression and Smell Testing as Diagnostic and Prognostic Biomarkers in Parkinson’s Disease Study (PROBE) study from 22 US tertiary care centers. 202 DAT-confirmed cases with de novo PD and 138 controls were enrolled in the Parkinson’s Progression Markers Initiative (PPMI) between July 2010 and November 2012 from 22 US and international tertiary care centers. Main Outcome Measures. Association of intracellular SNCA transcript abundance with PD estimated on analog and digital expression platforms. Results. Reduced levels of SNCA transcripts were associated with early-stage clinical PD, neuroimaging-confirmed PD, and untreated, neuroimaging-confirmed PD in accessible, peripheral blood cells from a total of 863 individuals. SNCA expression was reduced by 17%, 22%, and 16% in cases compared to controls in the HBS, PROBE, and PPMI study with P values of 0.004, 0.025, and 0.018, respectively, after adjusting for clinical, hematological, and processing covariates. Specific SNCA transcripts with long 3’ untranslated regions (UTR) and those skipping exon 5 are implicated in the accumulation and mitochondrial targeting of α-synuclein protein in Parkinson’s pathology. These transcript isoforms were linked to PD through digital expression analysis. Individuals in the lowest quartile of SNCA expression values had covariate-adjusted odds ratios for PD of 2.14 (95% C. I. 1.1-4.1), 4.5 (95% C. I. 1.3-15), and 2.1 (1.1-4.0) compared to individuals in the highest quartile of expression values in the HBS, PROBE, and PPMI study, respectively. Conclusions and Relevance. Reduced levels of SNCA expression, particularly of disease-relevant transcripts with extended 3’ UTR or exon 5 skipping, are associated with early-stage PD. These findings support a potential role for SNCA as a transcriptional marker of PD and may have implications for patient stratification and risk assessment.
2015-06-01 | GSE57475 | GEO
Project description:Parkinson's disease (PD) is a neurodegenerative disease characterized by bradycardia, static tremor, rigidity and postural instability. At present, the current knowledge remains inadequate for the connection between the disease severity and peripheral immune response. In the present study, using single-cell RNA sequencing (scRNA-seq), we profiled peripheral blood mononuclear cells (PBMCs) from clinical cases, including 2 early PD, 2 advance PD and 2 matched controls, representing five major immune cell subsets: T cells (CD4+, CD8+), monocytes, B cells, natural killer (NK) cells and hematopoietic stem cells (HSCs). The characteristic alterations of cell subset proportions were disentangled, in which T cells and NK cells were declined in the progression of PD. We further enlarged the sample size and collected peripheral blood samples of 14 normal individuals, 21 early and 14 advance PD patients. T cells and NK cells showed an obvious reduction in the blood samples as the disease proceeded. Moreover, NK cells infiltration into cerebral motor cortex indicated by immunostaining of human brain sections evidenced the close communication existing between peripheral immune response and central nervous system. Importantly, NK cells participated in numerous common immune-related biological processes. Strikingly, NK cell-specific XCL2 that was specifically expressed in cluster 6 was further identified and positively correlated with the PD severity. All these findings delineated the critical role of peripheral adaptive immune response, especially mediated by NK cells, in the pathogenesis of PD, providing clues of immune-related biomarkers or therapeutic targets during PD progression in future investigations.
2024-10-09 | GSE223138 | GEO
Project description:In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The goal was to identify splice isoforms whose expression is altered in whole blood of early-stage ParkinsonM-bM-^@M-^Ys disease patients compared to healthy and neurodegenerative disease controls. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples, 4 of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 10 healthy controls. Thirteen splice variants were confirmed in quantitative polymerase chain reactions and used to classify blinded samples from ParkinsonM-bM-^@M-^Ys disease patients and controls with 90% accuracy and 94% sensitivity. In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples and 20 control samples including 4 cases of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 12 healthy controls. Splice isoforms differentially expressed in PD vs any other control group were identified and validated using real-time quantitative PCR on two independent sets of 33 coded and 53 blinded samples.
2012-12-01 | E-GEOD-34287 | biostudies-arrayexpress
Project description:Bevacizumab beyond progression has been proven to be safe in the community setting (BRiTE) and in the post-marketing study (BEAT), and confirmed its efficacy and safety in the first line with all regimens of chemotherapy. A total of 1,953 patients were treated in BRiTE. At median follow-up of 17.5 mo, there were 1,369 1st PD and 839 deaths. Among patients with 1st PD, 65.2% received any 2nd-line chemotherapy, 34.8% received cetuximab, and 53.8% received BBP. In a multivariate analysis, Bevacizumab beyond first progression and exposure to any 2nd-line chemotherapy were independently associated with increased overall survival (both p < 0.0001). Bevacizumab beyond progression appears to be associated with longer overall in BRiTE.
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Project description:The given data set is the first deep sequencing transcriptome-wide data set of human Parkinson's disease (PD) patients RNA. The data set was produced from blood leukocytes of PD patients, from the same patients following deep brain stimulation (DBS), and from matched healthy control volunteers. Post-DBS samples were taken from the patients while being on electrical stimulation (ON-Stim), and following one hour off of electrical stimulation (OFF-Stim state). We have previously shown that gene expression changes, and in particular, alternative splicing changes, are observed in blood leukocytes and may contribute to PD and being subjected to regulation following DBS. Here, SOLiD RNA-Seq was applied to study the transcriptome of PD patients. Exon- and junction-level analyses revealed deep insight into both differential expression and alternative splicing regulation in PD blood leukocytes prior to and following DBS both on and off electrical stimulation. This transcriptome genome-wide data obtained through high-throughput sequencing of RNA produced from human Parkinson's disease (PD) patients blood leukocytes prior to treatment and following deep brain stimulation (DBS) neurosurgical treatment may yield insights into the molecular mechanisms that underlie the pathogenesis of PD and treatment efficacy. It may further enable the development of future diagnostics and therapeutics for PD.
2014-07-16 | GSE42608 | GEO
Project description:Poliquin2013 - Energy Deregulations in
Parkinson's Disease
Encoded non-curated model. Issues:
- Fluxes, reactions, parameters and species properly encoded
but Figure 2 not successfully simulated.
- Unpaired values in Table 5 and Matlab Code (S5 and S6
Supplementary Material): Vm_ldh_r, Vm_t_lac, Km_ldh_nadh, Vm_cdh,
Vm_cd, Vm_fh, Cm_ldh_f,Vm_sdh and Vm_pdh
- Confusing parameter t2 on unitpulseSB; is it T_p_off or
(T_p_off + T_p_on)?
This model is described in the article:
Metabolomics and in-silico
analysis reveal critical energy deregulations in animal models
of Parkinson's disease.
Poliquin PO, Chen J, Cloutier M,
Trudeau LÉ, Jolicoeur M.
PLoS ONE 2013; 8(7): e69146
Abstract:
Parkinson's disease (PD) is a multifactorial disease known
to result from a variety of factors. Although age is the
principal risk factor, other etiological mechanisms have been
identified, including gene mutations and exposure to toxins.
Deregulation of energy metabolism, mostly through the loss of
complex I efficiency, is involved in disease progression in
both the genetic and sporadic forms of the disease. In this
study, we investigated energy deregulation in the cerebral
tissue of animal models (genetic and toxin induced) of PD using
an approach that combines metabolomics and mathematical
modelling. In a first step, quantitative measurements of
energy-related metabolites in mouse brain slices revealed most
affected pathways. A genetic model of PD, the Park2 knockout,
was compared to the effect of CCCP, a complex I blocker. Model
simulated and experimental results revealed a significant and
sustained decrease in ATP after CCCP exposure, but not in the
genetic mice model. In support to data analysis, a mathematical
model of the relevant metabolic pathways was developed and
calibrated onto experimental data. In this work, we show that a
short-term stress response in nucleotide scavenging is most
probably induced by the toxin exposure. In turn, the robustness
of energy-related pathways in the model explains how genetic
perturbations, at least in young animals, are not sufficient to
induce significant changes at the metabolite level.
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2015-02-25 | MODEL1410060000 | BioModels