Marked Reduction of AKT1 Expression and Deregulation of AKT1-associated Pathways in Peripheral Blood Mononuclear Cells of Schizophrenia Patients
Transcriptomics Dataset
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General Information
AccessionGSE27383
TitleMarked Reduction of AKT1 Expression and Deregulation of AKT1-associated Pathways in Peripheral Blood Mononuclear Cells of Schizophrenia Patients
DescriptionRecent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia patients. We therefore examined PBMC expression levels of AKT1 in schizophrenia patients versus controls, and examined whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients. We performed a case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N=43) as compared to controls (N=29). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR)= 0.05). Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool. From each participant 30 ml of blood was drawn into heparinized tubes. All blood samples were obtained between 10.00 and 11.00 am to minimize diurnal variation. PBMCs were isolated by Ficoll gradient separation, started within 20 minutes after the drawing of blood and performed with minimum time variation. Cells were subsequently disrupted (Qiashredder kit; Qiagen), and RNA was isolated (RNeasy minikit; Qiagen) with an additional DNAse digestion step (RNase-free DNase set; Qiagen), all according to the manufacturers protocol, diluted in nuclease free water, and frozen at 80 C before use. Before freezing, RNA purity and quantity was assessed with the NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies). After thawing the isolated RNA was biotinylated into cRNA using the One-Cycle Target Labeling and Control Reagents Kit (Affymetric Co) according to the manufacturers protocol. Before hybridisation RNA quality and integrity was assessed using the Agilent 2100 BioAnalyzer (Agilent). Biotinylated cRNA was hybridized to the Affymetrix Human Genome U133 plus 2.0 GeneChip microarray containing 54,675 probe sets (Affymetrix Co). Each sample was individually biotinylated and hybridized to an individual microarray. Biotinylation was performed in batches with randomisation of patients and controls according to their ratios across the batches. The arrays were scanned and analyzed using Affymetrix Microarray Suite 4.2 software. Scanning was performed in three batches with randomization of patients and controls according to their ratios across the batches.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27383
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Keyword
Dataset Accession

Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset

Dataset Accession
Tool Name
Direction
Geneset

Interaction network and enrichment analysis of genes downregulated in schizophrenia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in schizophrenia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes downregulated in schizophrenia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in schizophrenia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Small molecules which mimic schizophrenia
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse schizophrenia
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic schizophrenia
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse schizophrenia
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in schizophrenia
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in schizophrenia
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
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