Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers.

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Tuberculosis (TB) remains a global health challenge, with latent infection progressing to active disease in a significant minority.
• Current diagnostic and prognostic biomarkers for TB progression are limited, hindering effective patient care and disease control.
• Biomarker development traditionally relies on transcriptomics, but integrating epigenetics and proteomics offers a more comprehensive understanding of host response.

Purpose of the Study:

• To investigate differences in DNA methylation, gene expression (transcriptome), and protein levels (proteome) in monocytes and granulocytes between active TB patients and healthy latent TB infection (LTBI) individuals.
• To explore the potential of multi-platform biosignatures for understanding the host response to Mycobacterium tuberculosis.
• To identify potential epigenetic and proteomic biomarkers for monitoring TB disease progression.

Main Methods:

• Pilot study analyzing DNA methylome, transcriptome, and proteome in isolated monocytes and granulocytes.
• Comparison of molecular profiles between TB patients and healthy LTBI controls.
• Statistical enrichment analysis using predefined gene sets to understand underlying biological mechanisms.

Main Results:

• First insights into epigenetic and proteomic diversity in TB patients and LTBI controls were obtained, despite small sample size.
• Functional differences between LTBI and active TB phenotypes were consistent across DNA methylation, transcriptome, and proteome platforms.
• Differences were observed in the transcriptome, proteome, and notably, the DNA methylome of monocytes and granulocytes between TB patients and controls.

Conclusions:

• Host response regulation in TB involves not only transcriptional but also epigenetic (DNA methylation) and microRNA-mediated mechanisms.
• The findings support the value of multi-omics approaches, particularly large-scale DNA methylome studies, for TB research.
• Future large-scale studies should consider variations related to gender, age, and cell type in their design.