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Published on: April 5, 2017
Screening of potential biomarkers for distinguishing between latent and active tuberculosis in children using
Meng Shao1, Fang Wu1, Jie Zhang2
1Department of Pathophysiology, Shihezi University School of Medicine/The Key Laboratory of Xinjiang Endemic and Ethnic Diseases.
Insights
This study identifies key blood gene markers to help diagnose active tuberculosis (TB) in children, improving upon current methods. These findings offer potential for new, rapid, non-sputum diagnostic tools for childhood TB.
Area of Science:
- Genomics and Bioinformatics
- Pediatric Infectious Diseases
- Molecular Diagnostics
Background:
- Tuberculosis (TB) remains a major global cause of childhood illness and death.
- Current diagnostic methods for childhood TB, particularly non-sputum-based approaches, are limited.
- Blood transcriptional profiling offers a promising avenue for diagnosing and predicting TB progression.
Purpose of the Study:
- To identify potential diagnostic gene markers for differentiating latent tuberculosis infection (LTBI) from active TB in children.
- To analyze blood transcriptome data from children using bioinformatics tools.
- To evaluate the diagnostic accuracy of identified candidate gene markers.
Main Methods:
- Downloaded and analyzed whole blood RNA sequencing datasets (GSE39939, GSE39940) from the Gene Expression Omnibus database.
- Utilized GEO2R for identifying differentially expressed genes (DEGs) between LTBI and active TB.
- Performed Gene Ontology and KEGG pathway analysis, constructed protein-protein interaction networks, and assessed diagnostic value using ROC curves.
Main Results:
- Identified 265 DEGs (79 upregulated, 186 downregulated) between LTBI and active TB in children.
- Highlighted 15 core genes involved in neutrophil activation and immune defense pathways.
- Several genes (e.g., TLR2, FPR2, MMP9, CEACAM8, FCGR1A, ARG1, HP, LCN2, ADCY3) demonstrated significant discriminatory power (AUCs ranging from 0.78 to 0.88).
Conclusions:
- The study identified several genes with high potential as non-sputum diagnostic markers for childhood tuberculosis.
- These candidate markers could facilitate the development of novel diagnostic tools for pediatric TB.
- Further validation is warranted to establish these genes in clinical diagnostic settings.
Abstract:
Tuberculosis (TB) is one of the leading causes of childhood morbidity and death globally. Lack of rapid, effective non-sputum diagnosis and prediction methods for TB in children are some of the challenges currently faced. In recent years, blood transcriptional profiling has provided a fresh perspective on the diagnosis and predicting the progression of tuberculosis. Meanwhile, combined with bioinformatics analysis can help to identify the differentially expressed genes (DEGs) and functional pathways involved in the different clinical stages of TB. Therefore, this study investigated potential diagnostic markers for use in distinguishing between latent tuberculosis infection (LTBI) and active TB using children's blood transcriptome data.From the Gene Expression Omnibus database, we downloaded two gene expression profile datasets (GSE39939 and GSE39940) of whole blood-derived RNA sequencing samples, reflecting transcriptional signatures between latent and active tuberculosis in children. GEO2R tool was used to screen for DEGs in LTBI and active TB in children. Database for Annotation, Visualization and Integrated Discovery tools were used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. STRING and Cytoscape analyzed the protein-protein interaction network and the top 15 hub genes respectively. Receiver operating characteristics curve was used to estimate the diagnostic value of the hub genes.A total of 265 DEGs were identified, including 79 upregulated and 186 downregulated DEGs. Further, 15 core genes were picked and enrichment analysis revealed that they were highly correlated with neutrophil activation and degranulation, neutrophil-mediated immunity and in defense response. Among them TLR2, FPR2, MMP9, MPO, CEACAM8, ELANE, FCGR1A, SELP, ARG1, GNG10, HP, LCN2, LTF, ADCY3 had significant discriminatory power between LTBI and active TB, with area under the curves of 0.84, 0.84, 0.84, 0.80, 0.87, 0.78, 0.88, 0.84, 0.86, 0.82, 0.85, 0.85, 0.79, and 0.88 respectively.Our research provided several genes with high potential to be candidate gene markers for developing non-sputum diagnostic tools for childhood Tuberculosis.
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