TY - JOUR T1 - Identification of eight-protein biosignature for diagnosis of tuberculosis JF - Thorax JO - Thorax DO - 10.1136/thoraxjnl-2018-213021 SP - thoraxjnl-2018-213021 AU - Qianting Yang AU - Qi Chen AU - Mingxia Zhang AU - Yi Cai AU - Fan Yang AU - Jieyun Zhang AU - Guofang Deng AU - Taosheng Ye AU - Qunyi Deng AU - Guobao Li AU - Huihua Zhang AU - Yuhua Yi AU - Ruo-Pan Huang AU - Xinchun Chen Y1 - 2020/03/21 UR - http://thorax.bmj.com/content/early/2020/03/22/thoraxjnl-2018-213021.abstract N2 - Background Biomarker-based tests for diagnosing TB currently rely on detecting Mycobacterium tuberculosis (Mtb) antigen-specific cellular responses. While this approach can detect Mtb infection, it is not efficient in diagnosing TB, especially for patients who lack aetiological evidence of the disease.Methods We prospectively enrolled three cohorts for our study for a total of 630 subjects, including 160 individuals to screen protein biomarkers of TB, 368 individuals to establish and test the predictive model and 102 individuals for biomarker validation. Whole blood cultures were stimulated with pooled Mtb-peptides or mitogen, and 640 proteins within the culture supernatant were analysed simultaneously using an antibody-based array. Sixteen candidate biomarkers of TB identified during screening were then developed into a custom multiplexed antibody array for biomarker validation.Results A two-round screening strategy identified eight-protein biomarkers of TB: I-TAC, I-309, MIG, Granulysin, FAP, MEP1B, Furin and LYVE-1. The sensitivity and specificity of the eight-protein biosignature in diagnosing TB were determined for the training (n=276), test (n=92) and prediction (n=102) cohorts. The training cohort had a 100% specificity (95% CI 98% to 100%) and 100% sensitivity (95% CI 96% to 100%) using a random forest algorithm approach by cross-validation. In the test cohort, the specificity and sensitivity were 83% (95% CI 71% to 91%) and 76% (95% CI 56% to 90%), respectively. In the prediction cohort, the specificity was 84% (95% CI 74% to 92%) and the sensitivity was 75% (95% CI 57% to 89%).Conclusions An eight-protein biosignature to diagnose TB in a high-burden TB clinical setting was identified. ER -