Transcriptional Profiling and Deriving a Seven-Gene Signature That Discriminates Active and Latent Tuberculosis: An...

Area of Science:

• Genomics
• Infectious Diseases
• Biomarker Discovery

Background:

• Tuberculosis (TB) is a significant global infectious disease caused by Mycobacterium tuberculosis.
• Distinguishing between active TB (ATB) and latent TB infection (LTBI) is crucial for effective treatment and control.
• Current diagnostic methods can be limited in differentiating these stages.

Purpose of the Study:

• To identify a gene expression signature for differentiating ATB from LTBI.
• To discover a potential blood-based biomarker for TB diagnosis.
• To analyze transcriptional profiles in individuals with ATB and LTBI.

Main Methods:

• Reanalyzed microarray datasets (GSE37250, GSE19491) from African cohorts.
• Performed differential gene expression analysis using BRB ArrayTool.
• Conducted pathway enrichment analysis (DAVID) and protein-protein interaction network construction (STRING).
• Validated a seven-gene signature using ROC curve analysis.

Main Results:

• Identified 375 upregulated and 152 downregulated differentially expressed genes (DEGs) between ATB and LTBI.
• Discovered a seven-gene signature (5 upregulated, 2 downregulated) with high diagnostic accuracy.
• The gene signature demonstrated sensitivity of 80-100% and specificity of 80-95% (AUC 0.84-1).
• Enriched pathways included IFN-stimulated genes and NOD-like receptor signaling for upregulated genes.

Conclusions:

• A novel seven-gene signature effectively discriminates between active TB and latent TB infection.
• This gene signature holds promise as a sensitive and specific biomarker for TB diagnosis.
• Further validation in diverse populations is warranted to confirm clinical utility.