Relationship between DNA Methylation Profiles and Active Tuberculosis Development from Latent Infection: a Pilot...

Area of Science:

• Genomics and Molecular Biology
• Infectious Diseases
• Biomarker Discovery

Background:

• Latent tuberculosis infection (LTBI) is a significant reservoir for active tuberculosis (TB) cases.
• Effective management of LTBI requires rapid and accurate tools to differentiate active TB from LTBI.
• Current diagnostic methods for distinguishing active TB from LTBI can be improved with novel biomarkers.

Purpose of the Study:

• To identify DNA methylation profiles as potential biomarkers for discriminating active TB from LTBI.
• To evaluate the diagnostic performance of identified differentially methylated CpGs (dmCpGs) in distinguishing active TB from LTBI.

Main Methods:

• Retrospective analysis of genomewide DNA methylation profiles using the Infinium MethylationEPIC BeadChip array.
• Comparison of DNA methylation levels between individuals with LTBI who developed active TB and LTBI controls.
• Identification and evaluation of differentially methylated CpGs (dmCpGs) using receiver operating characteristic (ROC) analysis.

Main Results:

• Eight dmCpGs were identified, with six in hypermethylated genes and two in hypomethylated genes.
• Individual dmCpGs showed areas under the curve (AUC) ranging from 0.72 to 0.84.
• A combination of four dmCpGs (cg02206980 + cg02214623 + cg12159502 + cg12321798) achieved the highest performance with an AUC of 0.88, 93.33% sensitivity, and 86.67% specificity.

Conclusions:

• DNA methylation levels show potential as diagnostic biomarkers for differentiating active TB from LTBI.
• The identified combination of four dmCpGs demonstrates promising diagnostic accuracy.
• Further validation in larger, independent populations is necessary to confirm these findings.