Characterization of whole blood gene expression profiles in sickle-cell disease patients using globin mRNA reduction
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
AccessionGSE16728
TitleCharacterization of whole blood gene expression profiles in sickle-cell disease patients using globin mRNA reduction
DescriptionRoom temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70%% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable. Keywords: Microarrays, PAXgene, globin reduction, whole blood, PBMC
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16728
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 sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes downregulated in sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes downregulated in sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in sickle cell anemia
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Small molecules which mimic sickle cell anemia
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse sickle cell anemia
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic sickle cell anemia
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse sickle cell anemia
The L1000 database was queried in order to identify small molecule perturbations which rev...
per page
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.