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

Author

Listed:
  • Adrienne Chang

    (Cornell University)

  • Conor J. Loy

    (Cornell University)

  • Daniel Eweis-LaBolle

    (Cornell University)

  • Joan S. Lenz

    (Cornell University)

  • Amy Steadman

    (Inc.)

  • Alfred Andgrama

    (World Alliance for Lung and Intensive Care Medicine in Uganda)

  • Nguyen Viet Nhung

    (National Lung Hospital)

  • Charles Yu

    (De La Salle Medical and Health Sciences Institute)

  • William Worodria

    (World Alliance for Lung and Intensive Care Medicine in Uganda)

  • Claudia M. Denkinger

    (University Hospital Heidelberg & German Center of Infection Research)

  • Payam Nahid

    (University of California San Francisco)

  • Adithya Cattamanchi

    (University of California San Francisco
    University of California Irvine)

  • Iwijn De Vlaminck

    (Cornell University)

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.

Suggested Citation

  • 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 , 2024. "Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49245-6
    DOI: 10.1038/s41467-024-49245-6
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    References listed on IDEAS

    as
    1. Humphrey Mulenga & Chambrez-Zita Zauchenberger & Erick W Bunyasi & Stanley Kimbung Mbandi & Simon C Mendelsohn & Benjamin Kagina & Adam Penn-Nicholson & Thomas J Scriba & Mark Hatherill, 2020. "Performance of diagnostic and predictive host blood transcriptomic signatures for Tuberculosis disease: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 15(8), pages 1-17, August.
    2. Kuhn, Max, 2008. "Building Predictive Models in R Using the caret Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 28(i05).
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