Deciphering a TB-related DNA methylation biomarker and constructing a TB diagnostic classifier

Abstract

We systemically identified tuberculosis (TB)-related DNA methylation biomarkers and further constructed classifiers for TB diagnosis. TB-related DNA methylation datasets were searched through October 3, 2020. Limma and DMRcate were employed to identify differentially methylated probes (DMPs) and regions (DMRs). Machine learning methods were used to construct classifiers. The performance of the classifiers was evaluated in discovery datasets and a prospective independent cohort. Eighty-nine DMPs and 24 DMRs were identified based on 67 TB patients and 45 healthy controls from 4 datasets. Nine and three DMRs were selected by elastic net regression and logistic regression, respectively. Among the selected DMRs, two regions (chr3: 195635643–195636243 and chr6: 29691631–29692475) were differentially methylated in the independent cohort (p = 4.19 × 10 −5 and 0.024, respectively). Among the ten classifiers, the 3-DMR logistic regression classifier exhibited the strongest performance. The sensitivity, specificity, and area under the curve were, respectively, 79.1%, 84.4%, and 0.888 in the discovery datasets and 64.5%, 90.3%, and 0.838 in the independent cohort. The differential diagnostic ability of this classifier was also assessed. Collectively, these data showed that DNA methylation might be a promising TB diagnostic biomarker. The 3-DMR logistic regression classifier is a potential clinical tool for TB diagnosis, and further validation is needed.

An updated HACOR score for predicting the failure of noninvasive ventilation: a multicenter prospective observational study

“…The data from the training cohort were used to update the HACOR score. First, we selected variables via elastic net regularization, using logistic models and tenfold cross-validation, selecting the regularization parameter λ when binomial deviation was within one standard error of the minimum [ 23 , 24 ]. Collinearity between continuous variables was identified if the absolute value of the correlation coefficients was > 0.7 [ 25 ].…”

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

“…In accordance, some reports have shown changes in human methylome during TB or in response to BCG. Lyu et al conclude that DNA methylation might be a promising TB diagnostic biomarker, as they identified TB-related targets differentially methylated by logistic regression and elastic net regression that were validated by bisulfite conversion and PCR (Lyu et al, 2022). DNA methylation has been also associated to anti-mycobacterial FIGURE 4 ROC curve analyses for evaluation of the predictive value of -53 CpG methylation on disease status.…”

“…Lyu et al. conclude that DNA methylation might be a promising TB diagnostic biomarker, as they identified TB-related targets differentially methylated by logistic regression and elastic net regression that were validated by bisulfite conversion and PCR ( Lyu et al., 2022 ). DNA methylation has been also associated to anti-mycobacterial activity in PBMCs from BCG-vaccinated individuals ( Verma et al., 2017 ).…”

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