Gene signature discovery and systematic validation across diverse clinical cohorts for TB prognosis and response to treatment
Fig 3
Systematic model validation using TB progression cohorts.
(A) The distributions of TB scores generated by the full model, stratified by categorical interval to disease (datapoints n = 1281), and (B) clinically defined TB states (datapoints n = 137) are shown in the violin plot. Individual datapoints are plotted as a point in the violin plot. P–values were calculated using the Mann–Whitney U test with Bonferroni correction (ns, p < 1; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001). (C–D) Receiver operating characteristic curves depict diagnostic performance of the model for incipient TB, (C) stratified by time intervals to disease (< 3, < 6, <12, <18, < 24, < 30 months) and (D) mutually exclusive time intervals to disease (0–3, 3–6, 6–12, 12–18, 18–24, 24–30 months). (E) The distributions of TB scores generated by the full model, stratified by different TB disease stages (HC, LTBI, and ATB), other lung disease (OLD) and viral infection (VI), are visualized in the violin. (F) Area under the curve and 95% confidence intervals for each interval to disease are also shown. Diagnostic performance of the model in differentiating between ATB versus HC, LTBI, OLD, and/or viral infection (VI) using a pooled dataset of all 57 collected cohort studies (S1 Table) (datapoints n = 6290) are showed in ROC curves.