A DNA Methylation Signature From Buccal Swabs to Identify Tuberculosis Infection

Abstract

Abstract Background Tuberculosis (TB) is among the largest infectious causes of death worldwide, and there is a need for a time- and resource-effective diagnostic methods. 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 patients with pulmonary TB (n = 7), TB-exposed persons (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. Last, we used machine learning to identify a panel of 7 CpG sites discriminative for TB and developed a TB classifier. In the validation cohort, the classifier performed with an area under the curve of 0.94, sensitivity of 0.92, and specificity of 1. Conclusions In summary, the result from this study shows clinical implications of using DNAm signatures from buccal swabs to explore new diagnostic strategies for TB.