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Abstract

Background

Tuberculosis (TB) is amongst the largest infectious causes of death worldwide and there is a need for a time- and resource-effective diagnostic method. In this novel and exploratory study, we show the potential of using buccal swabs to collect human DNA and investigate the DNA methylation (DNAm) signatures as a diagnostic tool for TB.

Methods

Buccal swabs were collected from pulmonary TB patients (n= 7), TB exposed (n= 7), and controls (n= 9) in Sweden. Using Illumina MethylationEPIC array the DNAm status was determined.

Results

We identified 5644 significant differentially methylated CpG sites between the patients and controls. Performing the analysis on a validation cohort of samples collected in Kenya and Peru (patients, n=26; exposed, n=9; control, n=10) confirmed the DNAm signature. We identified a TB consensus disease module, significantly enriched in TB-associated genes. Lastly, we used machine learning to identify a panel of seven CpG sites discriminative for TB and developed a TB classifier. In the validation cohort the classifier performed with an AUC of 0.94, sensitivity of 0.92, and specificity of 1.

Conclusion

In summary, the result from this study shows clinical implications of using DNAm signatures from buccal swabs to explore new diagnostic strategies for TB.

Graphical Abstract
Graphical Abstract
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Tuberculosis, DNA methylation, classifier, biosignature, buccal swabs
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© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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  • Supplementary data

    • Supplementary data

    jiae333_Supplementary_Data - zip file