Figure 12. The final 6-protein panel differentiates TB from both HC and ORI in a separate clinical cohort.

(A–F) Box-and-whisker plots of the 6 proteins in the panel in pulmonary TB compared with HC and ORI by proximity extension assay. Boxes show median values and interquartile ranges and whiskers show minimum to maximum values. Statistical differences were calculated using 1-way ANOVA with Tukey’s multiple-comparison test for data with a Gaussian distribution and Kruskal-Willis test with Dunn’s multiple-comparison test for nonparametrically distributed data. (G) Receiver operating characteristic (ROC) curve of the 6-protein panel distinguishing pulmonary TB from HCs. The 6-protein combined panel AUC = 0.882 (95% CI: 0.796–0.968). Full coordinates in Supplemental Table 16. (H) ROC curve of the 6-protein panel distinguishing pulmonary TB from ORI, AUC = 0.876 (95% CI: 0.765–0.987). Full coordinates in Supplemental Table 17. (I) Classification grid illustrating diagnostic performance of the 6-protein panel distinguishing pulmonary TB from HCs, demonstrating a sensitivity of 75.0% (95% CI: 54.8%–88.6%), specificity of 83.3% (95% CI: 64.5%–93.7%), and correct classification in 79.3% of cases in this cohort. (J) Classification grid illustrating diagnostic performance of the 6-protein panel distinguishing pulmonary TB from other respiratory infection, demonstrating a sensitivity of 92.9% (95% CI: 75.0%–98.8%), specificity of 78.9% (95% CI: 53.9%–93.0%), and correct classification in 87.2% of cases in this cohort. All ROC curves and classification grids were generated using SPSS v28.0.1.0 after binary logistic regression for combined proteins. AUC was calculated under nonparametric assumption. TB was set as the positive test outcome and the test direction such that a larger test result indicates a more positive test. NPX, normalized protein expression (log₂ scale); AUC, area under the curve; HC, healthy control (n = 30); TB, tuberculosis (n= 29); ORI, other respiratory infection (n = 19); ADA2, adenosine deaminase 2; CD14, monocyte differentiation antigen CD14; LRG1, leucine-rich α-2-glycoprotein; TNFSF13B, tumor necrosis factor ligand superfamily member 13B; vWF, von Willebrand factor. NS, P > 0.05; *P ≤ 0.05; ***P ≤ 0.001; ****P ≤ 0.0001.