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Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis

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Title: Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis
Authors: Adrienne Chang, Conor J. Loy, Daniel Eweis-LaBolle, Joan S. Lenz, Amy Steadman, Alfred Andgrama, Nguyen Viet Nhung, Charles Yu, William Worodria, Claudia M. Denkinger, Payam Nahid, Adithya Cattamanchi, Iwijn De Vlaminck
Source: Nature Communications, Vol 15, Iss 1, Pp 1-8 (2024)
Publisher Information: Nature Portfolio, 2024.
Publication Year: 2024
Collection: LCC:Science
Subject Terms: Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-024-49245-6
Access URL: https://doaj.org/article/b8b998ef5de540aa99fffdd6bd7bf167
Accession Number: edsdoj.b8b998ef5de540aa99fffdd6bd7bf167
Database: Directory of Open Access Journals
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  Data: 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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