Yang Q, Chen Q, Zhang M, et al. - Currently, Mycobacterium tuberculosis (Mtb) antigen-specific cellular responses form the basis of biomarker-based tests for diagnosing TB. As this approach is not efficient in diagnosing TB, especially for patients who lack etiological evidence of the disease, researchers here assessed three cohorts for a total of 630 individuals, including 160 individuals to screen protein biomarkers of TB, 368 individuals to establish and test the predictive model and 102 individuals for biomarker validation. Using pooled Mtb-peptides or mitogen, they stimulated whole blood cultures, and using an antibody-based array, simultaneous analysis was performed of 640 proteins within the culture supernatant. Then they developed 16 candidate biomarkers of TB recognized during screening into a custom multiplexed antibody array for biomarker validation. A two-round screening strategy led to identification of an eight-protein biosignature to diagnose TB in a high-burden TB clinical setting. The eight-protein biomarkers identified were: I-TAC, I-309, MIG, Granulysin, FAP, MEP1B, Furin and LYVE-1.