ROS-related genes as potential diagnostic biomarkers in tuberculosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE313408 | GEO | 2026/02/01
REPOSITORIES: GEO
Similar Datasets
Project description:More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, protein biomarkers to help diagnosis TB, which is critical in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One biomarker, serum CXCL1, met the World Health Organization’s Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune mediators and four proteins corresponding to a subset of highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB.
2021-07-29 | GSE179417 | GEO
Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with active versus latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 T cells isolated from individuals with active TB (at diagnosis and 2 months post treatment), latent TB, as well as from TB negative healthy controls. Overall, we found specific gene signatures for each cohort that could successfully discriminate between individuals with active TB at diagnosis, treated active TB, latent TB and healthy controls.
2021-05-11 | GSE161829 | GEO
Project description:: Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which is crucial the discovery of effective diagnostic biomarkers. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into 3 experimental groups – healthy controls (Controls), Latent TB infection (LTBI) and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between Controls and TB patients. The AUC, specificity and sensitivity, determined by ROC statistical analysis of the model composed by four of these proteins considering both proteomic sets, were 0.96; 93% and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes, were submitted to ROC analysis. An AUC=1 was determined with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling 1 protein and 4 metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature has correctly assigned the 12 controls and 12 patients used only for prediction (AUC=1, specificity=100% and sensitivity=100%). This multi-omics approach has revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.
2023-03-11 | PXD037341 | Pride
Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of monocyte subsets associated with active versus latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical (CD14-CD16+) monocytes isolated from individuals with active TB (at diagnosis and 2 months post treatment), latent TB, as well as from TB negative healthy controls. Overall, we found specific gene signatures for each monocyte subset that could successfully discriminate between individuals with active TB at diagnosis, treated active TB, latent TB and healthy controls.
2023-01-03 | GSE185372 | GEO
Project description:Tuberculosis (TB) remains one of the world’s major infectious diseases affecting nations with limited public health resources. Multidrug resistance development has seriously compromised therapeutic treatment choices. The pathology of latent TB shows evidence of a reservoir of Mycobacterium tuberculosis (Mtb) in the lungs of affected individuals. If the pathogen is contained by the immune system, no overt disease symptoms occur. The environmental and internal triggers leading to disease reactivation are not well understood. Proteomic investigations of blood plasma and sputum derived from subjects with active TB versus latent TB versus healthy individuals may yield new biomarkers and, when surveying larger longitudinally monitored cohorts, may discriminate infection outcomes in an endemic setting.
2021-05-26 | PXD012412 | Pride
Project description:We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina’s DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS). DNA methylation levels were validated in an independent cohort of 64 TB patients and 24 HS. Microarray analysis identified 1028 DMLs in TB patients versus HS, and 3747 DMLs in TB patients after versus before anti-TB treatment, while autophagy was the most enriched signaling pathway. In the validation cohort, PARP9 and miR505 genes were hypomethylated in the TB patients versus HS, while RASGRP4 and GNG12 genes were hypermethylated, with the former two further hypomethylated in those with delayed sputum conversion, systemic symptoms, or far advanced lesions. MRPS18B and RPTOR genes were hypomethylated in TB patients with pleural involvement. RASGRP4 gene hypermethylation and RPTOR gene down-regulation were associated with high mycobacterial burden. TB patients with WIPI2/GNG12 hypermethylation or MRPS18B/FOXO3 hypomethylation had lower one-year survival. In vitro ESAT6 and CFP10 stimuli of THP-1 cells resulted in DNA de-methylation changes of the PARP9, RASGRP4, WIPI2, and FOXO3 genes. In conclusions, aberrant DNA methylation over the PARP9/miR505/RASGRP4/GNG12 genes may contribute to the development of active pulmonary TB disease and its clinical phenotypes, while aberrant DNA methylation over the WIPI2/GNG12/MARPS18B/FOXO3 genes may constitute a determinant of long-term outcomes.
2020-04-30 | GSE118469 | 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:Background: Mechanisms by which prior tuberculosis (TB) increases long-term risk for cancer, cardiovascular, and neurological disorders remain unclear, particularly in people with HIV (PWH). This study investigated DNA methylation (DNAm) patterns and associated pathways in PWH with and without prior TB infection. Methods: DNAm was analyzed in blood samples from 30 PWH (10 with prior latent TB infection [LTBI], 10 with previous successfully treated active TB, and 10 with no TB) using the Illumina MethylationEPIC BeadChip covering over 850,000 CpG sites. Epigenetic age was estimated, and age acceleration was calculated. Differentially methylated CpGs (dmCpGs) and regions (DMRs) were identified, and functional enrichment analyses for Gene Ontology, KEGG pathways, PANTHER database, and gene set enrichment analysis (DisGeNET, dbGaP) were performed. Statistical significance was set at a false discovery rate (FDR) of <0.05. Results: PWH exhibited significant epigenetic age acceleration, with a mean of 19.32 ± 10.82 years greater than chronological age. This accelerated aging was more pronounced in individuals with any prior TB infection (21.60 ± 12.03 years) compared to those without TB (17.42 ± 9.38 years). In the prior active TB vs. no TB comparison, 7,461 dmCpGs were identified, corresponding to 150 DMRs (p<0.05), with top associated genes including GRAMD1C (hypomethylation), DPP6 (hypermethylation), and HDAC4 (hypomethylation). In the LTBI vs. no TB comparison, 8,598 dmCpGs were observed, corresponding to 39 DMRs (p<0.05), associated with genes such as PLEKHG5 (hypermethylation), STK32C (hypermethylation), and SPATC1L. When comparing any prior TB (active or latent) to no TB, 71,774 dmCpGs and 14 DMRs were identified, including genes like PLEKHG5, KCNN3, and BRSK2. Pathway analyses of prior TB (active or latent) vs. no TB revealed enrichment in neurogenesis, neuron differentiation, axon guidance, and neuroactive ligand signaling. Additional enriched pathways included those related to platelet activation, vascular muscle contraction, and chemokine signaling. Cancer-related pathways such as proteoglycans in cancer, small cell lung cancer, prostate cancer, breast cancer, hepatocellular carcinoma, and thyroid cancer were also enriched. PANTHER analysis showed consistent enrichment in the Wnt signaling pathway and inflammation-mediated pathways across compared groups. DisGeNET analysis linked prior TB DNAm patterns to lymphoid leukemia, while dbGaP analysis identified associations with phenotypes like asthma, body mass index, tunica media, and lymphocyte count Conclusion: Prior TB infection in PWH is associated with distinct DNAm changes in pathways related to neural function, cardiovascular health, and cancer risk, and is linked to more pronounced epigenetic age acceleration, suggesting epigenetic mechanisms for TB-related long-term complications.
2025-08-27 | GSE304107 | 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: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.
2014-05-01 | GSE39939 | GEO