Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis

Qiao-Ling Ruan, Qing-Luan Yang, Yi-Xin Gao, Jing Wu, Si-Ran Lin, Jing-Yu Zhou, Ling-Yun Shao, Sen Wang, Qian-Qian Liu, Yan Gao, Ning Jiang, Wen-Hong Zhang, Qiao-Ling Ruan, Qing-Luan Yang, Yi-Xin Gao, Jing Wu, Si-Ran Lin, Jing-Yu Zhou, Ling-Yun Shao, Sen Wang, Qian-Qian Liu, Yan Gao, Ning Jiang, Wen-Hong Zhang

Abstract

www.clinicaltrials.gov (NCT02430259).

Keywords: RNA sequencing; Tuberculosis; biomarker; interferon-gamma; latent tuberculosis infection; peripheral blood mononuclear cell.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Flow diagram of data collection and analysis. PBMC: peripheral blood cells; GO analysis: Gene Ontology analysis; KEGG analysis: Kyoto Encyclopedia of Genes and Genomes analysis; WGCNA: Weighted correlation network analysis; GSEA: Gene-set enrichment analysis.
Figure 1.
Figure 1.
Flow diagram of data collection and analysis. PBMC: peripheral blood cells; GO analysis: Gene Ontology analysis; KEGG analysis: Kyoto Encyclopedia of Genes and Genomes analysis; WGCNA: Weighted correlation network analysis; GSEA: Gene-set enrichment analysis.
Figure 2.
Figure 2.
Transcriptional patterns of peripheral blood mononuclear cells defining stimulated and un-stimulated, TB progressors and non-progressors. (A) Principal component analysis diagram. (B) Unsupervised hierarchical clustering of transcribed genes and differentially expressed over 1.5-fold for 12 PBMC samples. (C) Volcano plot shows the upregulated and downregulated transcribed genes between TB progressors and non-progressors. (D) Venn diagrams showing overlaps of TB-specific genes changes between TB progressors and non-progressors. TB progressors: P107 and P129; Non-progressors: P102, P105, P170 and P173. A: PBMCs stimulated by TB antigen, N: PBMCs incubated without TB antigen.
Figure 2.
Figure 2.
Transcriptional patterns of peripheral blood mononuclear cells defining stimulated and un-stimulated, TB progressors and non-progressors. (A) Principal component analysis diagram. (B) Unsupervised hierarchical clustering of transcribed genes and differentially expressed over 1.5-fold for 12 PBMC samples. (C) Volcano plot shows the upregulated and downregulated transcribed genes between TB progressors and non-progressors. (D) Venn diagrams showing overlaps of TB-specific genes changes between TB progressors and non-progressors. TB progressors: P107 and P129; Non-progressors: P102, P105, P170 and P173. A: PBMCs stimulated by TB antigen, N: PBMCs incubated without TB antigen.
Figure 3.
Figure 3.
Different gene expression and functional enrichment analysis of TB progressors and non-progressors using un-stimulated (left) and stimulated (right) samples. (A–B) DEGs was applied to GO analysis in BP, CC and MF. (C–D) DEGs was applied to KEGG analysis.
Figure 3.
Figure 3.
Different gene expression and functional enrichment analysis of TB progressors and non-progressors using un-stimulated (left) and stimulated (right) samples. (A–B) DEGs was applied to GO analysis in BP, CC and MF. (C–D) DEGs was applied to KEGG analysis.
Figure 4.
Figure 4.
Modular transcriptional signatures of TB progressors compared to non-progressors. Fold enrichment scores derived using QuSAGE are depicted, with red and blue indicating modules over- or under-expressed. Colour intensity and size represent the degree of enrichment.
Figure 4.
Figure 4.
Modular transcriptional signatures of TB progressors compared to non-progressors. Fold enrichment scores derived using QuSAGE are depicted, with red and blue indicating modules over- or under-expressed. Colour intensity and size represent the degree of enrichment.
Figure 5.
Figure 5.
Normalized expression value of twenty discriminatively expressed TB-specific genes related with type II interferon between TB progressors (red) and non-progressors (blue). Kruskal–Wallis tests were used to compare the differences among the two groups. **Significant difference: 0.001 P < 0.01; ***Significant difference: P < 0.0001. Log2 fold changes and P value were listed on the right.
Figure 5.
Figure 5.
Normalized expression value of twenty discriminatively expressed TB-specific genes related with type II interferon between TB progressors (red) and non-progressors (blue). Kruskal–Wallis tests were used to compare the differences among the two groups. **Significant difference: 0.001 P < 0.01; ***Significant difference: P < 0.0001. Log2 fold changes and P value were listed on the right.

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