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. 2020 May 25;10:8629. doi: 10.1038/s41598-020-65043-8

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Diagnostic performance of RISK6 as a triage test. (a and b) ROC curves depicting diagnostic performance of RISK6 (a) and the ACS 11-gene signature (b), for discrimination between active TB cases and Mtb-infected controls in HIV-negative or HIV-positive individuals. RISK6 was measured by qRT-PCR on RNA from whole blood. Shaded areas depict the 95% CI. The boxes in the top left corner represent the optimal (solid line) and minimum (dotted line) criteria set out in the target product profile for a screening/triage test for TB. (c) Comparison of RISK6 signature scores in Mtb-infected controls and active TB cases in HIV-negative or HIV-positive individuals. P-values were calculated using the Mann-Whitney U test. Horizontal lines represent medians; boxes represent the IQR and whiskers the range. Dots represent individual sample scores. (d) Relative differences in RISK6 transcript expression levels between HIV-negative and HIV-positive Mtb-infected controls (green) or active TB cases (orange). Dots depict medians and error bars the 95% CI, calculated from 1000 bootstrapped Ct values. The dashed line represents zero. (e) Comparison of RISK6 signature scores, by blind prediction, in patients with definite TB (with rigorous microbiological confirmation), patients with probable TB and in patients with other respiratory diseases (ORD). Horizontal lines depict medians, boxes the IQR and the whiskers the range. Violin plots depict the density of data points. P-values were computed by Mann-Whitney U test. (f) Receiver operating characteristic (ROC) curve depicting discrimination between diagnostic performance, by blind prediction of RISK6, measured by qRT-PCR in definite TB patients and patients with other respiratory diseases (ORD). Shaded areas depict the 95% CI. (g) ROC curves depicting RISK6 discrimination between definite TB and ORD participants of the ScreenTB and AE-TBC cohorts stratified into participants with no history of prior TB (black), or in those with a history of prior TB (red). Shaded areas depict the 95% CI.