Whole Blood Transcriptional Response to Early Acute HIV
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Damien Chaussabel
PROVIDER: E-GEOD-29429 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The objective of this study is to: 1) Characterize the transcriptional signature of early acute HIV infection. 2) Eucidate the evolution of the signature in both anti-retroviral treated and untreated populations over a 24 week time course. 3) Correlate clinical and disease related parameters to heterogenaity in the transcriptional signature to identify pathways explaining clinical heterogeneity 4) Compare the acute signature of HIV infection to other acute viral signatures.
2015-05-18 | GSE29429 | GEO
Project description:This series regroups different datasets (training set, test set, validation set, longitudinal set, separated cell set) to identify and characterise a specific transcriptional signature for patients with active TB, distinct from patients with latent TB and healthy controls. The training set dataset was used to identify a whole blood transcriptional signature for active TB patients in London, across a range of ethnicity. This signature was then validated in an independent cohort of patients, also recruited in London (the test set), and then further confirmed in an additional independent cohort recruited in Cape Town, South Africa (validation set), in order to confirm that the defined signature was present in both high (Cape Town, South Africa) and medium incidence regions (London, UK). The longitudinal dataset was then used to explore how successful TB treatment modifies this transcriptional signature. The separated cell set compares the transcriptional profiles in purified cell subsets (neutrophils, monocytes and T cells) to assess which cell types are contributing to the whole blood signature, and in what way. These studies may ultimately help to improve the diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 weeks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques such as bronchoalveolar lavage (BAL). In some cases (30%) the bacill cannot be grown from sputum or BAL. Any diagnostic tool would need to be valid across a range of ethnicities, and be valid in both high and low incidence countries. A further aim was to determine whether latent TB patients have a distinct homogeneous or heterogeneous signature, since it is not currently possible to determine using present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria have been cleared, are still present but are controlled by an active immune response, or to predict which patients will develop active TB. Defining heterogeneity in the latent TB patients would be an important step in developing diagnostics which could detect those most at risk of developing active TB, and thus enable targeted preventive therapy. The latter situation may be determined if Latent patients have a blood transcriptional signature similar to that in Active patients. The transcriptional signature in whole blood and cell subsets from Active TB patients may also provide information as to the factors leading to immunopathogenesis, thus possibly identifying therapeutic targets. The transcriptional profile in latent TB may give information regarding protective factors controlling the infection, important for vaccine development. Finally, definition of a transcriptional signature which responds to therapy could facilitate the development of surrogate biomarkers for drug or vaccine studies. Since any active TB signature may reflect common inflammatory responses evoked during many diseases, we also performed analysis of significance, comparing transcriptional profiles from patients with TB to those from patients with other bacterial and inflammatory diseases to identify a TB specific signature. The resulting signature was then tested against patients normalized to their own controls from 7 independent datasets: TB (Training and Validation Sets), Staphylococcus infection, Group A Streptococcus infection, Still's disease, and adult and pediatric SLE. This SuperSeries is composed of the following subset Series: GSE19435: Transcriptional profiles in Blood of patients with Tuberculosis - Longitudinal Study GSE19439: Blood Transcriptional Profiles in Active and Latent Tuberculosis UK (Training Set) GSE19442: Blood Transcriptional Profiles of TB in South Africa GSE19443: Blood Transcriptional Profiles of Active TB (UK Test Set Separated) GSE19444: Blood Transcriptional Profiles of Active and Latent TB (UK Test Set) GSE22098: Whole blood transcriptional profiles of patients with active tuberculosis (TB) and other inflammatory and infectious diseases Active Pulmonary TB: PTB - All patients were confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum or bronchoalvelolar lavage fluid. Latent TB: LTB - All patients were screened at a tuberculosis clinic, being either new entrants to the UK from endemic countries or being household contacts of infectious cases, or in the case of the validation set recruited in South Africa, were residents of a high incidence country. All UK patients were positive by tuberculin skin test (>14mm if BCG vaccinated, >5mm if not vaccinated) and were also positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). The South African latent TB patients were all positive by Interferon-Gamma Release assay (IGRA); specifically Quantiferon Gold In-Tube Assay. Latent patients had no clinical, radiological or microbiological evidence of active infection and were asymptomatic. Healthy controls - these were volunteers without exposure to TB who were negative by both tuberculin skin test (<15mm if BCG vaccinated, <6mm if unvaccinated); and IGRA (as described above). Experimental variables : Patient group: Active PTB; Latent TB, Healthy controls (BCG vaccinated and unvaccinated). Ethnicity - a wide range of ethnic groups is represented. The active PTB group incorporates a range of smear positive and smear negative disease and a spectrum of disease extent/severity. Experimental methods: Whole blood was collected into Tempus tubes (Applied Biosystems, Foster City, CA, USA) and stored between -20degrees Celsius and -80 degrees Celsius before RNA extraction. For the training set cohort, and the active TB patients baseline samples in the longitudinal cohort, total RNA was isolated from whole blood using the PerfectPure RNA Blood kit (5 PRIME Inc, Gaithersburg, MD, USA). For the separated cell samples, total RNA was isolated using the Qiagen RNeasy Mini Kit. For all other cohorts Total RNA was isolated from whole blood using the MagMAX 96 well RNA isolation kit (Applied Biosystems, Foster City, CA, USA). Isolated total RNA was then globin reduced using the GLOBINclear 96-well format kit (Ambion, Austin, TX, USA) according to the manufacturer's instructions. Total and globin-reduced RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Biotinylated, amplified RNA targets (cRNA) were then prepared from the globin-reduced RNA using the Illumina CustomPrep RNA amplification kit (Ambion, Austin, TX, USA). Labeled cRNA was hybridized overnight to Sentrix HT12 V3 BeadChip arrays (>48,000 probes, Illumina Inc, San Diego, CA, USA), washed, blocked, stained and scanned on an Illumina BeadStation 500 following the manufacturer's protocols. Illumina's BeadStudio version 2 software was used to generate signal intensity values from the scans, substract background, and scale each microarray to the median average intensity for all samples (per-chip normalisation). This normalised data was used for all subsequent data analysis.
2010-08-11 | E-GEOD-19491 | biostudies-arrayexpress
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment. CVID subjects who fulfilled the standard diagnostic criteria, including significantly decreased levels of IgG, IgA, and/or IgM and poor or absent specific antibody production were enrolled. They were classified into, with or without characteristic inflammatory complications, as previously designated (hematologic or organ-specific autoimmunity, biopsy-proven granulomatous disease, or interstitial lung disease, lymphoid hyperplasia/ with splenomegaly or gastrointestinal inflammatory disease). 59 patients were included in the training set and 21 healthy controls and for test set 32 patients and 15 healthy controls. Disease controls included 6 X-linked agammaglobulinemia (XLA) patients and 15 healthy controls were included. Blood was taken before the interval intravenous immune globulin (Ig) infusions, or between subcutaneous administrations. The blood was collected using Tempus tubes and processed for microarray analysis.
2014-01-09 | E-GEOD-51404 | biostudies-arrayexpress
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment. CVID subjects who fulfilled the standard diagnostic criteria, including significantly decreased levels of IgG, IgA, and/or IgM and poor or absent specific antibody production were enrolled. They were classified into, with or without characteristic inflammatory complications, as previously designated (hematologic or organ-specific autoimmunity, biopsy-proven granulomatous disease, or interstitial lung disease, lymphoid hyperplasia/ with splenomegaly or gastrointestinal inflammatory disease). 59 patients were included in the training set and 21 healthy controls and for test set 32 patients and 15 healthy controls. Disease controls included 6 X-linked agammaglobulinemia (XLA) patients and 15 healthy controls were included. Blood was taken before the interval intravenous immune globulin (Ig) infusions, or between subcutaneous administrations. The blood was collected using Tempus tubes and processed for microarray analysis.
2014-01-09 | E-GEOD-51405 | biostudies-arrayexpress
Project description:We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after the sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-group) were included as a control group, which were effectively treated with cART (virological controlled and CD4+ T-cell counts over 500) for an extended period. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs).
2021-05-05 | E-MTAB-10232 | biostudies-arrayexpress
Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111±22 days (Mean±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection. The initial 347 miRNA array was performed in 11 RPs, 6 CPs and 4 corresponding matched normal controls (training group); and only the miRNAs differentially expressed between RPs and CPs (P<0.05) in training group were detected in a subsequent validation group (19 RPs versus 10 CPs). miRNAs differentially expressed in 17 early HIV infected patients (including 11 RPs and 6 CPs) and 4 healthy controls in training cohort were firstly identified. Then, miRNAs differed RPs from CPs were compared in both training and validation cohort.
2013-05-01 | E-GEOD-44332 | biostudies-arrayexpress
Project description:Whole genome transcriptional profiling by microarray of blood taken from HIV-negative healthy volunteers (n=15), and HIV patients before (n=24) and after three months of anti-retroviral therapy (n=17). This submission includes two human whole genome Agilent Array Designs: A-AGIL-28 and A-GEOD-20844. Each of the individual raw array files are included as well as a single processed file representing the data matrix of all the merged and normalised data for the probes that are shared by the two array designs.
2021-02-26 | E-MTAB-8897 | biostudies-arrayexpress
Project description:This study aimed to examine if early life exercise could normalize the reduced heart mass we have previously observed in the adult hearts from growth restricted rats. We investigated the molecular pathways using microarray analysis to explain how endurance exercise in early life might be regulating the sustained increase in heart mass we have observed in these rats in adulthood. At 5 weeks of age, male WKY rats were allocated to one of the following exercise treatments: remained sedentary with post mortem (PM) at 9 or 24 weeks, early exercise training (from 5-9 weeks of age) with PM at 9 or 24 weeks, or later exercise training (from 20-24 weeks of age) with PM at 24 weeks (n=8 males/group). Exercise training involved treadmill running 5 days/ week for 4 weeks. Running duration progressively increased from 20 up to 60 minutes per day, with the treadmill speed set at 15 m/min for the first week and 20 m/min thereafter. At 9 or 24 weeks of age rats were killed with an intraperitoneal injection of Ilium Xylazil-20 (30 mg/kg) and Ketamine (225 mg/kg). The rats in the 9 week old early exercise and 24 week old later exercise groups were killed 72 hours following the last bout of treadmill running. Total RNA was obtained from the whole-hearts for analysis
2015-12-09 | GSE75781 | GEO
Project description:Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC). We isolated circulating endothelial cells from patients experience acute myocardial infartion and healthy cohorts, and measured gene expression using the HG-133U_PLUS_2 microarray Circulating endothelial cells were isolated from patients experiencing acute myocardial infarction (n=49) and from healthy cohorts (n=50). The patients were separated into a discovery cohort (n=43) for biomarker discovery and model training; and into a validation cohort (n=56) for biomarker validation and model testing.
2015-02-28 | E-GEOD-66360 | biostudies-arrayexpress
Project description:To identify signature genes that help distinguish (1) sepsis from non-infectious causes of systemic inflammatory response syndrome, (2) between Gram-positive and Gram-negative sepsis. Experiment Overall Design: A total of 70 critically ill patients (46 sepsis and 24 control) were enrolled in a single-centre observational study. Gene-expression profiling was performed using Affymetrix microarray (U133plus2) with 54,675 transcript. Data was divided into a training set (n=35) and a validation set (n=35). A molecular signature was developed in the training set and was then validated in the validation set.
2009-04-12 | E-GEOD-9960 | biostudies-arrayexpress