生物标志物
肺结核
核糖核酸
寄主(生物学)
计算生物学
细胞
主机响应
生物
病毒学
医学
免疫学
免疫系统
基因
遗传学
病理
作者
Adrienne Chang,Conor Loy,Daniel Eweis-LaBolle,Joan Sesing Lenz,Amy Steadman,Adrienne Chang,Nhung Viet Nguyen,Charles Yu,William Worodria,Claudia M. Denkinger,Payam Nahid,Adithya Cattamanchi,Iwijn De Vlaminck
标识
DOI:10.1038/s41467-024-49245-6
摘要
Abstract Tuberculosis (TB) remains a leading cause of death from an infectious disease worldwide, partly due to a lack of effective strategies to screen and triage individuals with potential TB. Whole blood RNA signatures have been tested as biomarkers for TB, but have failed to meet the World Health Organization’s (WHO) optimal target product profiles (TPP). Here, we use RNA sequencing and machine-learning to investigate the utility of plasma cell-free RNA (cfRNA) as a host-response biomarker for TB in cohorts from Uganda, Vietnam and Philippines. We report a 6-gene cfRNA signature, which differentiates TB-positive and TB-negative individuals with AUC = 0.95, 0.92, and 0.95 in test, training and validation, respectively. This signature meets WHO TPPs (sensitivity: 97.1% [95% CI: 80.9-100%], specificity: 85.2% [95% CI: 72.4-100%]) regardless of geographic location, sample collection method and HIV status. Overall, our results identify plasma cfRNA as a promising host response biomarker to diagnose TB.
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