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Genome-wide profiling of altered gene expression in the neocortex of Alzheimer's disease (exon level)

ABSTRACT: We investigated genome-wide gene alterations in the temporal cortex of a well-characterized cohort of AlzheimerM-bM-^@M-^Ys disease (AD) patients using Affymetrix exon arrays. The AD patients and controls are subjects originally recruited into OPTIMA (Oxford Project to Investigate Memory and Ageing). Subjects underwent annual clinical and neuropsychological assessments, including the Cambridge Cognitive Examination (CAMCOG). Among subjects who died with autopsy consent given by next of kin, 1 cm3 blocks of grey matter from BA22 were dissected from fresh frozen brains of AD subjects. Tissues from elderly controls, followed longitudinally in life and with CAMCOG scores >80 at the last assessment before death, were collected. Affymetrix exon array was carried out in 8 control and 8 AD samples. The samples processed in each hybridization run were matched for AD vs. control, sex and postmortem interval (PMI) as far as possible. This submission includes the exon-level analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Michelle Tan

PROVIDER: E-GEOD-37264 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide profiling of altered gene expression in the neocortex of Alzheimer's disease (gene level)

Project description:We investigated genome-wide gene alterations in the temporal cortex of a well-characterized cohort of AlzheimerM-bM-^@M-^Ys disease (AD) patients using Affymetrix exon arrays. The AD patients and controls are subjects originally recruited into OPTIMA (Oxford Project to Investigate Memory and Ageing). Subjects underwent annual clinical and neuropsychological assessments, including the Cambridge Cognitive Examination (CAMCOG). Among subjects who died with autopsy consent given by next of kin, 1 cm3 blocks of grey matter from BA22 were dissected from fresh frozen brains of AD subjects. Tissues from elderly controls, followed longitudinally in life and with CAMCOG scores >80 at the last assessment before death, were collected. Affymetrix exon array was carried out in 8 control and 8 AD samples. The samples processed in each hybridization run were matched for AD vs. control, sex and postmortem interval (PMI) as far as possible. This submission includes the gene-level analysis.

2012-04-12 | E-GEOD-37263 | biostudies-arrayexpress

Expression data from non-demented controls (NDCs) and Alzheimer's disease (AD) patients

Project description:AD is the leading cause of dementia in the elderly. However, disease etiology is still practically unknown. To gain insight into the molecular mechanisms underlying this disease we used the Affymetrix exon arrays to profile the alternative splicing landscape of human entorhinal cortex samples from AD patients and controls. We found a few hundred events of alternative spicing that characterize the AD entorhinal cortex and may have profound effect on the pathogenesis of this disease. Expression was analyzed using Affymetrix Human Exon 1 S.T arrays samples from 3 female NDCs and 3 female AD patients were included in this study

2012-09-06 | E-GEOD-26972 | biostudies-arrayexpress

Effect of myotonic dystrophy on pre-mRNA alternative splicing in skeletal muscle

Project description:Misregulated alternative splicing appears to be a major factor in the pathogenesis of myotonic dystrophy. The present study was done to further explore alternative splicing in this condition by doing exon-level analysis of mRNA from skeletal muscle of 8 subjects with type 1 myotonic dystrophy, 7 subjects with type 2 myotonic dystrophy, 8 disease controls (subjects with facioscapulohumeral muscular dystrophy), and 8 healthy controls . The ratios of signals from the various exons of a gene provided an index of altered exon inclusion/exclusion that was independent of the overall expression of that gene. There were numerous transcripts for which there was evidence of abnormal alternative splicing in subjects with myotonic dystrophy. For many of these transcripts, the abnormal splicing was confirmed by an independent RT-PCR approach. 31 subjects, one sample per subject, four groups: healthy subjects (n = 8), facioscapulohumeral dystrophy (n = 8), type 1 myotonic dystrophy (n = 8), type 2 myotonic dystrophy (n = 7)

2013-06-15 | E-GEOD-47968 | biostudies-arrayexpress

Expression data from human THP-1 monocytes stimulated with increasing concentrations of arachidonic (AA) or oleic acid (OA).

Project description:Previous data indicated tha AA and OA modify global DNA methylation. This study analyzes the impact of these fatty acids on expression as a complement to array-based DNA methylation data. In this dataset, we include the expression data obtained from THP-1 monocyte stimulated with 1, 10 or 100uM AA or OA for 24h. RNA extracted from the same cells used for array-based DNA methylation analysis (see corresponding data in published article) was used to produce expression data by Affymetrix Human Exon 1.0 ST v2 Array

2014-04-27 | E-GEOD-57076 | biostudies-arrayexpress

Genome-wide analysis of differentially expressed genes and splicing isoforms in clear cell Renal Cell Carcinoma

Project description:In this study we performed a genome wide analysis of the entire complement of mRNAs in clear cell renal cell carcinomas (ccRCC) by means of the Affymetrix Exon Array platform. The analyses were performed both at gene and exon level. Under our parameters over 2,000 genes resulted differentially expressed, and about 250 genes resulted alternative spliced showing differential inclusion of specific cassette exons comparing tumor and non tumoral tissues. 20 total samples were used for exon array analysis: 10 ccRCC tumor sample (T) and their matched non-tumor (NT) kidney tissues samples. All exon array data were analyzed using Partek Genomic Suite 6.4 software (Partek). The robust multi-array average (RMA) algorithm was used for the gene- and exon-level intensity analyses. Data were M-oM-,M-^Altered to consider only those probe sets included in the M-bM-^@M-^\Core Meta-ProbesetM-bM-^@M-^]. Lists of genes and exons with significant variation of the expression levels were generated by using a 0.01 FDR criterion as a significant cutoff. Partek list of significant exon-level probesets (FDR corrected p-value < 0.01) and exon level ANOVA test list were used to create - by an ad hoc Python script - a database of significant probesets from Exon Array experiments. To make more stringent the analysis criteria we excluded from the final exon lists all those cases in which Exon Array revealed a significant change at gene-level. This database we created has been used to explore simple exon skipping events using as reference ASPicDB single exon skipping splicing events after mapping Affymetrix probesets on ASPicDB .gtf files. A single exon from the Partek list was defined significantly skipped only if its adjacent exons were not, by using 0.01 and 0.05 p-value criterions as a significant cutoff for the M-bM-^@M-^\skippedM-bM-^@M-^] and adjacent exons, respectively.

2013-09-06 | E-GEOD-47032 | biostudies-arrayexpress

ENCODE H1_ES cell phenotyping study

Project description:These samples are part of the ENCODE consortium’s proposed time-limited Pilot Study for confirmation of the utility of RNA abundance measurements as a standard reference phenotyping tool. Keywords: cell type comparison For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Each batch of H1-ES cells cultured by Cellular Dynamics International for use by the ENCODE labs was processed on Affymetrix Exon 1.0 ST arrays to obtain phenotyping data.

2009-02-16 | E-GEOD-14863 | biostudies-arrayexpress

Gene expression profiles of Hodgkin’s lymphoma cells

Project description:By using high-density DNA microarrays, we analyzed the gene-expression profile of Hodgkin's lymphoma cell lines. RNA was extracted from established Hodgkin's lymphoma cell lines and analyzed with Affymetrix Human Exon 1.0ST microarrays.

2013-07-16 | E-GEOD-47686 | biostudies-arrayexpress

Effects of vitamin D supplementation on alveolar macrophage gene expression

Project description:The objective of the overall study was to determine the effects of oral vitamin D supplementation on alveolar macrophages from human subjects. In this substudy, subjects treated with vitamin D (intervention group) in paired analysis had small, but significant effects on immune-related differential gene expression pre versus post supplementation. In this study, we obtained alveolar macrophages by bronchoalveolar lavage of subjects before and after a 3 month vitamin D trial. RNA for the array was obtained shortly after bronchoscopy. Randomized Controlled Trial: This is a substudy of paired samples of subjects treated with vitamin D. Each sample was studied once. 22 individuals were studied.

2014-04-08 | E-GEOD-56583 | biostudies-arrayexpress

Expression and Splicing Analysis of Myotonic Dystrophy and Other Dystrophic Muscle

Project description:The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls. For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4). Normal control RNAs were purchased commercially. .CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.

2016-01-05 | E-GEOD-48828 | biostudies-arrayexpress

Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR) [expression]

Project description:Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing only rarely targets canonical splicing acceptor, donor, and branch sites, it was found to affect splicing regulatory elements (SREs) within exons. Cassette exons were found to be significantly enriched with A-to-I RNA editing sites compared with constitutive exons. RNA-seq and exon-specific microarray revealed that ADAR knockdown in hepatocarcinoma and myelogenous leukemia cell lines leads to global changes in gene expression, with hundreds of genes changing their splicing patterns in both cell lines. This global change in splicing pattern cannot be explained by putative editing sites alone. Genes showing significant changes in their splicing pattern are frequently involved in RNA processing and splicing activity. Analysis of recently published RNA-seq data from glioblastoma cell lines showed similar results. Our global analysis reveals that ADAR plays a major role in splicing regulation. Although direct editing of the splicing motifs does occur, we suggest it is not likely to be the primary mechanism for ADAR-mediated regulation of alternative splicing. Rather, this regulation is achieved by modulating trans-acting factors involved in the splicing machinery. HepG2 and K562 cell lines were stably transfected with plasmids containing siRNA designed to specifically knock down ADAR expression (ADAR KD). This in order to examine how ADAR affects alternative splicing globally.

2013-06-15 | E-GEOD-47945 | biostudies-arrayexpress

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