Pulmonary hypertension (PH) is a serious complication of sickle cell disease (SCD) associated with increased mortality. Gene expression profiles of peripheral blood mononuclear cells (PBMC) have been studied in pulmonary arterial hypertension and in SCD. We hypothesized that a PBMC-derived gene signature in SCD patients may be utilized as a PH biomarker. Twenty-seven patients with homozygous SCD underwent transthoracic echocardiography and PBMC isolation. PH was defined as estimated right ventricular systolic pressure (RVSP)>30 mmHg with a peak tricuspid regurgitation velocity (TRV)>2.5m/s. Genome-wide gene expression profiles were correlated against PH severity using RVSP and TRV as surrogates, which yielded 631 potentially dysregulated transcripts.
A novel molecular signature for elevated tricuspid regurgitation velocity in sickle cell disease.
Disease, Race
View SamplesPost-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Overall design: Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)
Using Next-Generation Sequencing Transcriptomics To Determine Markers of Post-traumatic Symptoms: Preliminary Findings from a Post-deployment Cohort of Soldiers.
Sex, Subject
View SamplesA series of transfections was performed in Drosophila S2 cells to explore: 1) the types of target sites that Drosophila microRNAs recognize, 2) the relative functional efficacy of these sites in mediating repression, and 3) the determinants that allow some sites to have greater potency than others. 3p-seq was also performed to help reannotate and quantify the landscape of 3'' UTRs in Drosophila S2 cells. Overall design: Nine mRNA profiles were generated, with Drosophila S2 cells transfected with one of 6 microRNAs (miR-1, miR-4, miR-92a, miR-124, miR-263a, and miR-997). These samples were compared to 3 biological replicates of a mock transfection condition. 3p-seq data for S2 cells was also generated to help reannotate and quantify 3'' UTR isoforms.
Predicting microRNA targeting efficacy in Drosophila.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.
Specimen part
View SamplesEarly erythroid progenitors were isolated from mouse E14.5 fetal liver. After cell lysing, control IgG or RBP specific antibody were incubated with cell lysis. Immunoprecipitation followed by microarray experiments were carried out to identify transcripts that are immunoprecipitated by either control IgG or RBP specific antibody.
ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.
Specimen part
View SamplesGenome-wide transcriptome analysis was performed to understand the expression pattern of transcriptomes in tolerant and susceptible subtropical maize genotypes under waterlogging stress condition.
Genome-wide expression of transcriptomes and their co-expression pattern in subtropical maize (Zea mays L.) under waterlogging stress.
Specimen part, Treatment, Time
View SamplesExpression .CEL files from Affymetrix HG-U133A 2.0 arrays using DNA from 14 human cell lines derived from metastasized melanoma
Differences in global gene expression in melanoma cell lines with and without homozygous deletion of the CDKN2A locus genes.
Specimen part, Cell line
View SamplesWe find that treating mesenchymal NAMEC8 cells with cholera toxin (CTx) to elevate intracellular cAMP levels and activate PKA induces a mesenchymal-to-epithelial transition whereby the cells assume an epithelial state (N8-CTx). NAMEC8 cells undergo epigenetic reprogramming triggered by active PHF2, a histone demethylase, which demethylates H3K9me2 and H3K9me3 regions of epithelial genes silencing in the mesenchymal state Overall design: Performing RNASeq with HMLE (immortalized human mammary epithelial cells), their mesenchymal CD44hi counterparts, NAMEC8 and the CTx-reverted versions of NAMEC8 a.k.a N8-CTx
Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability.
No sample metadata fields
View SamplesMYB plays a critical role as a regulator of erythropoieisis. We have shown that MYB silences epsilon and gamma-globin expression in erythroid progenitors. We here examine erythroid cells at the basophilic erythroblast stage of differentiation with MYB shRNA or control lentiviral transduction prior to differentiation.
MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13.
Specimen part, Treatment
View SamplesThe mTOR (mammalian Target of Rapamycin) pathway is constitutively activated in Diffuse Large B-Cell Lymphoma (DLBCL). mTOR inhibition has been shown to have clinical activity in patients with DLBCL, although overall response rates remain low. We therefore evaluated differences in the transcriptome between DLBCL cell lines with differential sensitivity to the mTOR inhibitor Rapamycin, to (A) identify gene-expression patterns(GEP) capable of identifying sensitivity to Rapamycin, (B) understand the underlying mechanisms of resistance to Rapamycin in DLBCL and (C) identify bioactive molecules likely to synergize with mTOR inhibitors. Using Affymetrix HuGene ST 1.0 microarrays, we were able to identify a gene expression signature capable of accurately predicting sensitivity and resistance to Rapamycin in DLBCL cell lines. Pathway analysis identified the serine/threonine kinase Akt as central to the differentially-expressed gene network. Connectivity mapping of our datasets identified compounds targeting the AKT pathway with a high likelihood of reversing the GEP associated with resistance to Rapamycin. Specifically, we evaluated the HIV protease inhibitor (PI) Nelfinavir, which is known to have anti-cancer and Akt-inhibitory properties, as well as the small molecule Akt inhibitor MK-2206, for their potential to synergize with to Rapamycin in DLBCL. Nelfinavir and MK-2206 caused profound inhibition of cell viability in combination with Rapamycin in DLBCL cell lines. Low nanomolar concentrations of Rapamycin inhibited phosphorylation of Akt and also downstream targets of activated mTOR when used in combination with these Akt inhibitors. These findings have the potential to significantly improve patient selection for mTOR inhibitor therapy, and to improve rates and depths of response. More broadly, they support the use of global RNA expression and connectivity mapping to improve patient selection and identify synergistic drug combinations for cancer therapy.
Akt inhibitors MK-2206 and nelfinavir overcome mTOR inhibitor resistance in diffuse large B-cell lymphoma.
Cell line
View Samples