RNA seq analysis of Active TB and treatment after 6 &12 months
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA505338 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8185720_1.fastq.gz | Fastqsanger.gz | |||
| SRR8185720_2.fastq.gz | Fastqsanger.gz | |||
| SRR8185721_1.fastq.gz | Fastqsanger.gz | |||
| SRR8185721_2.fastq.gz | Fastqsanger.gz | |||
| SRR8185722_1.fastq.gz | Fastqsanger.gz |
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Project description:Tuberculosis (TB) is a chronic granulomatous disease caused by the pathogen Mycobacterium tuberculosis. The success of M. tuberculosis can be attributed to its ability to evade protective host immune responses and its recalcitrance to antimicrobial chemotherapy. Detailed understanding of protective host immune response to TB is still lacking and there are limited reports that characterize host responses to TB at the site of disease. Furthermore, although cure of the majority of patients treated with the standard 6-month multidrug regimen indicates that treatment is highly effective, approximately 4-10% of clinically cured patients will develop recurrent disease within the first 12 months after completing therapy. We therefore analyzed BALF supernatant proteomes from pulmonary TB patients and patients at the end of standard anti-TB treatment to gain a better understanding of the host response at the site of disease. This would not only aid our understanding of localised host responses during TB disease, but could allow us to identify protein signatures associated with active TB disease or clinical cure.
2021-11-03 | PXD018907 | Pride
Project description:Changes in the blood transcriptome upon treatment were studied in a cohort of 42 latent tuberculosis (TB) subjects and 8 active TB subiects. Samples were collected at diagnosis (prior the start of treatment) and post treatment and gene expression studied with Illumina microarrays. We hypothesize that individuals with latent TB at risk of developing active disease are immunologically closer to those with active TB and will thus display a blood transcriptomic signature similar to active TB subjects upon treatment. This signature should significantly differ from the one mounted by latent TB individuals at low risk of progression. Thus, monitoring blood transcriptomic changes following anti-TB therapy might inform on which latent TB subjects should be prioritized for receiving therapeutic intervention in order to prevent further transmission.
2021-12-08 | GSE152532 | GEO
Project description:While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38M-BM-0C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. A diagnosis of TB was only made when the CXR was consistent with TB9 and the child showed a positive clinical response to anti-TB treatment. Children were followed up clinically, radiologically and, in case of a negative TST at inclusion, by means of TST at six and 12 months after inclusion. LTBI was defined as a TST = 10mm and a positive QFT-GIT with a negative culture result on inclusion in the absence of radiological and clinical evidence of TB disease on inclusion as well as on t=6 and t=12 months. HC were children with a TST = 0 mm at inclusion and at t=6 and t=12 months. The HC had a negative QFT-GIT and a negative culture result at inclusion without radiological or clinical evidence of TB disease on inclusion nor on t=6 and t=12 months. TB patients were sampled before initiation of anti-TB treatment. Of three of the nine TB patients, a follow-up sample was taken when the patient was in anti-TB treatment for five months. All children were HIV-negative. 27 samples in total where analyzed, active TB infection (TB, n=9), Latent TB infection (LTBI, n=9) and healthy controls (HC, n=9) . Gene expression values were log2-transformed and differentially expressed genes were identified based on log2 fold changes (M-values). P values were calculated with a Bayes-regularized one-way ANOVA. Random Forest recursive feature elimination was used to find a signature geneset capable of discrimination active TB from latent TB and from non-infected individuals.
2013-02-05 | E-GEOD-41055 | biostudies-arrayexpress
Project description:While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38°C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. A diagnosis of TB was only made when the CXR was consistent with TB9 and the child showed a positive clinical response to anti-TB treatment. Children were followed up clinically, radiologically and, in case of a negative TST at inclusion, by means of TST at six and 12 months after inclusion. LTBI was defined as a TST = 10mm and a positive QFT-GIT with a negative culture result on inclusion in the absence of radiological and clinical evidence of TB disease on inclusion as well as on t=6 and t=12 months. HC were children with a TST = 0 mm at inclusion and at t=6 and t=12 months. The HC had a negative QFT-GIT and a negative culture result at inclusion without radiological or clinical evidence of TB disease on inclusion nor on t=6 and t=12 months. TB patients were sampled before initiation of anti-TB treatment. Of three of the nine TB patients, a follow-up sample was taken when the patient was in anti-TB treatment for five months. All children were HIV-negative.
2013-02-05 | GSE41055 | GEO
Project 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. Three milliliters of whole blood was collected in Tempus tubes from 12 pediatric streptococcus, 40 pediatric staphylococcus, 31 still’s disease, 82 pediatric systemic lupus erythematosus (SLE) and 28 adult SLE patients. RNA was extracted and globin reduced. Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Healthy controls were included to match patients’ demographic data. Genespring software was used to analyze active TB transcript signatures, comparing with healthy controls and other inflammatory and infectious diseases.
2010-08-11 | E-GEOD-22098 | biostudies-arrayexpress
Project description:Context: There is growing evidence on the role of epigenetic regulation of growth, and miRNAs potentially play a role. Objective: To identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months on treatment, and verify whether these early changes can predict growth response. Methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M,5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >±1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. Results: 16 miRNAs were up-regulated and 2 down-regulated at t+3 months. MiR-199a-5p (p=0.020), miR-335-5p (p=0.001), and miR-494-3p (p=0.026) were confirmed to be up-regulated at t+3. Changes were independent of peak GH values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters. Conclusion: miR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months on GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response.
2022-04-29 | GSE193450 | GEO
Project description:Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV co-infected persons. We aimed to investigate the mechanisms of ART-mediated prevention of TB in HIV and TB co-infected patients on antiretroviral therapy (ART), recruited in Khayelitsha, South Africa. RNA was extracted from whole blood collected in TempusTM Blood RNA tubes at day 0 and at 1, 3 and 6 months of ART. We first performed a pilot RNAseq experiment of 12 samples (3 patients at 4 timepoints) for 50 million reads to assess if samples with lower quality and/or quantity will still yield meaningful outputs and the minimum number of reads required for sufficient coverage. This was followed by a second RNAseq experiment of 35 samples with sufficient quality: 11 from day 0 and 24 from 6 months of ART, 8 of which are paired. However, only n=6 samples from day 0 and n=6 samples from 6 months of ART could be analyzed. Results indicated reduced immune activation at 6 months of ART compared to day 0 with significant fall in the Hallmark Interferon alpha, Interferon gamma and IL-6-JAK-STAT-signalling pathway genes. These results were supported by similar changes in soluble protein markers in the plasma. Overall, our data indicates that ART- induced decrease in immune activation may contribute to reduced susceptibility to tuberculosis in HIV-TB co-infected persons.
2021-02-17 | GSE158208 | GEO
Project 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.
2010-08-11 | GSE22098 | 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:Study to identify putative condition specific biomarkers
2018-11-14 | GSE122485 | GEO