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. 2021 Jul 15;11:14516. doi: 10.1038/s41598-021-93893-3

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Biomarker discovery. (a,b) Scatter plots of the sensitivity and specificity of all proteins on the microarray. Each dot represents one protein. Left panel: proteins present at different levels in the ATB-vs-LTBI (left panel) and ATB-vs-HC (right panel) comparisons. Red dots: proteins with (1) a discriminant ability (sensitivity + specificity − 100) > 10%; (2) a fold change > 2 and a p-value < 0.05; and (3) at least 90% specificity. (b) Microarray results and annotations of the 4 proteins selected as candidate biomarkers. (c) Box plots and ROC curves for each of the 4 candidate biomarkers. Left panels: box plots show that the signal intensities of the each candidate biomarker is significantly higher in the ATB group than in the HC and LTBI control groups. Right panel: ROC curves. The sensitivity and specificity values obtained at the optimal cut off value for each candidate biomarker are also shown. (d) Performance of the top biomarker panel, comprised of Rv0934, Rv3881c, Rv1860, and Rv1827. Orange and light blue lines represent samples scored as positive or negative, respectively. A sample was predicted as ATB positive when any of the four proteins in the panel was positive. The heatmap was drawn using the ‘pheatmap’ package (v1.0.12)²³.