Project description:The diagnosis of pediatric tuberculosis (TB) poses a challenge for clinical teams worldwide. TB-mediated changes in the expression of host genes in the peripheral blood can serve as diagnostic biomarkers and can provide better insights into the host immune mechanisms of childhood TB. Peripheral blood mononuclear cells (PBMCs) from children (n=102) with microbiologically confirmed TB disease, ΤΒ infection (ΤΒΙ), pneumonia, and healthy controls (HC) were stimulated with either the Purified Protein Derivative (PPD) or the Early Secretory Antigen 6kDa-Culture Filtrate Protein 10 (ESAT6-CFP10) complex of Mycobacterium tuberculosis (Mtb). RNA was extracted and quantified using gene expression microarrays. Differential expression analysis was performed comparing microbiologically confirmed TB to the other diagnostic groups for the stimulated and unstimulated samples. Using variable selection, we identified sparse diagnostic gene signatures; one gene (PID1) was able to distinguish TB from pneumonia after ESAT6-CFP10 stimulation with an AUC of 100% in the test set, while a combination of two genes (STAT1 and IFI44) achieved an AUC of 91.7% (CI95% 75.0%-100%) in the test set after PPD stimulation. The number of significantly differentially expressed (SDE) genes was higher when contrasting TB to pneumonia or HC in stimulated samples, compared to unstimulated ones, leading to a larger pool of candidate diagnostic biomarkers. Our approach provides enlightened aspects of peripheral TB-specific responses and can form the basis for a point of care test meeting the World Health Organization (WHO) Target Product Profile (TPP) for pediatric TB.

2024-10-16 | GSE249575 | GEO

Gene expression profiling identifies candidate biomarkers for active and latent tuberculosis

Project description:Tuberculosis (TB) is a serious infectious disease, but current methods of detection require improvement in sensitivity, efficiency or specificity. We conducted a microarray experiment, comparing the gene expression profiles in peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population. These differentially expressed genes may be potential biomarkers that can differentiate between active TB and latent infection.

2014-10-21 | GSE62525 | GEO

Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

Project description:Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis¬-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 132 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

2024-02-26 | GSE255724 | GEO

Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients

Project description:Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from longstanding adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Since obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. Methods: We compared microarrays and RT-PCR of blood cells from 28 AD children (<5yrs and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes/DEGs in blood (fold change/FCH>1.2 and false discovery rate/FDR<0.05) were then compared with skin DEGs. Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were upregulated in early pediatric AD blood, while IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss/TEWL), whereas Th2/Th17-induced IL19 was positively correlated with SCORAD. While a few RT-PCR-defined immune markers (IL13/CCL22) were increased in blood, as previously also reported for skin, there was minimal overlap based on gene array DEGs. Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile, but markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course allergic comorbidity development, and response to systemic medications.

2018-12-06 | GSE116486 | GEO

Whole blood transcriptional profiles of patients with active tuberculosis (TB) and other inflammatory and infectious diseases

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

A blood RNA signature for tuberculosis disease risk: a prospective cohort study

Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.

2016-03-22 | GSE79362 | GEO

Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

Project description:Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

| PRJNA1076232 | ENA