Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA138727 | ENA |
REPOSITORIES: ENA
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Project description:Tuberculosis (TB) is an ancient infectious disease that remains one of the major health threats in humans worldwide. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These gene signature analyses were employed for pathognomonic associations, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed, and functional gene clusters of immunoregulatory interactions provide detailed insights into the dysregulation of critical immune processes in TB. Transcriptomics thus (i) provides a robust system for identification and validation of biosignatures for TB diagnosis and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis. A total of 46 sputum smear and chest x-ray positive TB patients (TB), 25 latently infected healthy donors (LTBI, TB case contacts with Mantoux test induration >= 10mm) and 37 uninfected donors (NID, Mantoux test induration = 0mm) were included from a cohort in The Gambia. All subjects were HIV– and samples from TB patients were taken prior to chemotherapy. Whole blood RNA was extracted using the PAXgene Blood RNA Kit (PreAnalytix) and labeled with Agilents Fluorescent Linear Amplification Kit. Quantity and labeling efficiency were verified before hybridization of the samples to whole-genome 4×44k human expression arrays and scanned at 5 μm using an Agilent scanner.
2011-10-27 | E-GEOD-28623 | biostudies-arrayexpress
Project description:Tuberculosis (TB) is an ancient infectious disease that remains one of the major health threats in humans worldwide. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These gene signature analyses were employed for pathognomonic associations, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed, and functional gene clusters of immunoregulatory interactions provide detailed insights into the dysregulation of critical immune processes in TB. Transcriptomics thus (i) provides a robust system for identification and validation of biosignatures for TB diagnosis and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis.
2011-10-28 | GSE28623 | GEO
Project description:Tuberculosis (TB) remains the world’s top infectious killer. Understanding how immune mediators determine the outcome of Mycobacterium tuberculosis infection could facilitate the design of better therapies against this devastating disease. GM-CSF mediates protective immunity against TB but the underlying mechanisms remain elusive. To determine the molecular mechanisms underlying the protective role of GM-CSF during M. tuberculosis infection we performed RNA-sequencing analyses of whole blood and lung samples obtained from C57Bl/6 mice infected with HN878 and treated with anti-GM-CSF monoclonal antibody or isotype control. Uninfected mice were also treated and used as uninfected controls. Three weeks post-infection, whole blood and lungs were harvested from each individual mouse and processed for RNA-sequencing. Transcriptomic analyses revealed that during M. tuberculosis infection GM-CSF regulates the expression of genes associated with neutrophil recruitment and activation and type I IFN-inducible genes, which have been previously associated with TB pathogenesis. Further mechanistical studies showed that disease exacerbation driven by GM-CSF blockade during M. tuberculosis infection was type I IFN and neutrophil-dependent and that over-activation of neutrophils by type I IFN induced NET formation at the site of infection. NETs were also found in necrotic lung lesions from patients with pulmonary TB and type I IFN-driven NET formation correlated with increased disease susceptibility in different mouse models of TB. Our findings reveal an important immune network that may play a central role in determining TB outcome.
2020-09-07 | GSE141205 | GEO
Project description:Tuberculosis (TB) remains the world’s top infectious killer. Understanding how immune mediators determine the outcome of Mycobacterium tuberculosis infection could facilitate the design of better therapies against this devastating disease. GM-CSF mediates protective immunity against TB but the underlying mechanisms remain elusive. To determine the molecular mechanisms underlying the protective role of GM-CSF during M. tuberculosis infection we performed RNA-sequencing analyses of whole blood and lung samples obtained from C57Bl/6 mice infected with HN878 and treated with anti-GM-CSF monoclonal antibody or isotype control. Uninfected mice were also treated and used as uninfected controls. Three weeks post-infection, whole blood and lungs were harvested from each individual mouse and processed for RNA-sequencing. Transcriptomic analyses revealed that during M. tuberculosis infection GM-CSF regulates the expression of genes associated with neutrophil recruitment and activation and type I IFN-inducible genes, which have been previously associated with TB pathogenesis. Further mechanistical studies showed that disease exacerbation driven by GM-CSF blockade during M. tuberculosis infection was type I IFN and neutrophil-dependent and that over-activation of neutrophils by type I IFN induced NET formation at the site of infection. NETs were also found in necrotic lung lesions from patients with pulmonary TB and type I IFN-driven NET formation correlated with increased disease susceptibility in different mouse models of TB. Our findings reveal an important immune network that may play a central role in determining TB outcome.
2020-09-07 | GSE141192 | GEO
Project description:Purpose: The goal of the study was to integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signalling networks, relevant for rheumatoid arthritis (RA). Method:RNA-seq based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated RA patients, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of “connector” genes derived from pathway analysis was then tested for differential expression in the initial discovery cohort. Results: 11 qualifying genes were selected for pathway analysis and grouped into 2 evidence-based functional networks, containing 29 and 27 additional “connector” molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. 3 genes showed similar expression difference in both treated and non-treated RA patients and additional nine genes were differentially expressed in at least one patients’ group compared to healthy controls. Conclusion: Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes in the pathogenesis of RA.
2016-11-24 | GSE90081 | GEO
Project description:Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication in HIV-TB coinfected patients receiving combined antiretroviral therapy (cART). While monocytes/macrophages play major roles in both HIV- and TB-infection individually, a putative contribution of monocytes to the development of TB-IRIS remains unexamined. To investigate the possible functional contribution of monocytes to TB-IRIS pathogenesis, one of our first steps was to apply a genome-wide microarray analysis in monocytes of HIV-TB co-infected patients shortly after cART initiation. Based on the coparison of gene profiles between the TB-IRIS group and the control group, the modulated genes and pathways will be further investigated.
2013-07-08 | E-MEXP-3591 | biostudies-arrayexpress
Project description:Characterization of Tuberculosis (TB) progression, diagnosis and treatment response with blood transcriptional RNA-seq analyses. Focus and underlying host immunological response and identification of new signatures for TB early diagnosis and treatment monitoring response.
2021-09-04 | GSE157657 | GEO
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African adult populations. Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Adults were recruited from Cape Town, South Africa (n=300) and Karonga, Malawi (n=237) who were either HIV+ or HIV - with either active TB, LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2013-10-23 | E-GEOD-37250 | biostudies-arrayexpress
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in a paediatric cohort from Kenya Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Children were recruited from 2 hospitals in Coast Province, Kenya (n=157) who were either HIV+ or HIV - with either active TB (culture confirmed), active TB (culture negative), LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2014-05-01 | E-GEOD-39939 | biostudies-arrayexpress
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African paediatric populations. Transcriptional signatures were identified that distinguished active TB from LTBI, and active TB from other diseases. Children were recruited from Cape Town, South Africa (n=157) and Blantyre, Malawi (n=177) who were either HIV+ or HIV - with either active TB, LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2014-05-01 | E-GEOD-39940 | biostudies-arrayexpress