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GSE40553
Homo sapiens
204 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of UK blood transcriptional profiles before treatment to indentify changes that occur during (2 weeks, 2 months), at the end of treatment (6 months) and after treatment (12 months)
Publication Title
Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined.
Publication Title
Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Missense mutations in transcription factor GATA1 underlie several distinct forms of anemia and thrombocytopenia. Clinical severity depends on the site and type of substitution, and distinct substiutions of the same residue produce disparate phenotypes. To investigate the effect of GATA1 missense mutations on erythroid differentiation we expressed conditionally activated wild type or mutant versions of GATA1 in GATA1-null G1E cells.
Publication Title
Analysis of disease-causing GATA1 mutations in murine gene complementation systems.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 107 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Patients with HIV-associated TB are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 63 patients with HIV-associated TB, 33 of whom developed TB-IRIS. Of which transcriptomic profiling was performed using longitudinal whole blood RNA samples from 15 non-IRIS and 17 TB-IRIS patients. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified as early as week 0.5 (2-5 days post-ART) and predicted a downstream activation of proinflammatory cytokines. At the peak of IRIS (week 2), transcriptomic signatures were overrepresented by innate receptor signaling pathways including toll-like receptor, IL-1 receptor and TREM-1.
Publication Title
HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 498 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
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.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 274 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. The goals of this study include: 1. Identify a transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment; 2. Identify a specific transcript signature that discriminated active TB from other inflammatory and infectious diseases; 3. Classify TB signature using modular and pathway analysis tools.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This dataset aims to validate and confirm the signature identified in the training set. The aim of the experiment was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The aim of this study was to compare the transcriptional response to TB in regions of different incidence / prevalence.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This dataset aims to dissect the whole blood transcriptional signature by determining if elements of the whole blood signature are still present in purified cell subpopulations. We aimed to characterise the transcriptional response during TB and identify if cell subsets drove changes in whole blood cellular composition. The aim of the experiment was to define transcriptional signatures in neutrophils, monocytes, CD4+ and CD8+ cells from blood of active TB patients and healthy controls to distinguish the signature of active TB patients from each other and from healthy controls. This will help in the diagnosis of active tuberculosis, which normally relies on culture of the bacilli, which can take up to 6 weeks, sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 42 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The aim of the project was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB. The latter situation may be determined if Latent patients have a blood transcriptional signature similar to that in Active patients. The transcriptional signature in 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 as to the protective factors controlling the infection, thus important for monitoring vaccine development. A further aim was to examine the transcriptional blood profile of active TB patients at the time of recruitment (before drug treatment) and then subsequently at specific time points after drug treatment to determine whether the signature is extingsuihed with treatment and when. London is a site of intermediate burden of TB - the study was initiated in London, across a broad range of ethnicities to obtain a robust signature that could be used in different developing countries where there is a high burden TB disease.
Publication Title
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.
Sample Metadata Fields
Sex, Age, Race
View Samples