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Abstract: TB patients and 16 latently TB infected (LTBI) subjects enrolled as part of an ongoing household contact study. Differential gene expression and clustering analyses were performed and compared with explicit predictive testing of TB and LTBI individuals based on established gene signatures. We observed strong predictive performance of TB disease states based on expression of known gene sets (ROC AUC 0.9007-0.9879). Together, our findings indicate that previously reported classifiers generated from different ethnic populations can accurately discriminate active TB from LTBI in South Indian patients. Future work should focus on converting existing gene signatures into a universal TB gene signature for diagnosis, monitoring TB treatment, and evaluating new drug regimens.