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Predicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells

Author

Listed:
  • Noa Bossel Ben-Moshe

    (Weizmann Institute of Science)

  • Shelly Hen-Avivi

    (Weizmann Institute of Science)

  • Natalia Levitin

    (Weizmann Institute of Science)

  • Dror Yehezkel

    (Weizmann Institute of Science)

  • Marije Oosting

    (Radboud University Medical Center)

  • Leo A. B. Joosten

    (Radboud University Medical Center)

  • Mihai G. Netea

    (Radboud University Medical Center
    University of Bonn)

  • Roi Avraham

    (Weizmann Institute of Science)

Abstract

Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Advances in single cell RNA-sequencing (scRNA-seq) allow probing of these immune interactions, such as cell-type compositions, which are then interpreted by deconvolution algorithms using bulk RNA-seq measurements. However, not all aspects of immune surveillance are represented by current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we develop a deconvolution algorithm for inferring cell-type specific infection responses from bulk measurements. We apply our dynamic deconvolution algorithm to a cohort of healthy individuals challenged ex vivo with Salmonella, and to three cohorts of tuberculosis patients during different stages of disease. We reveal cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and human infection outcomes.

Suggested Citation

  • Noa Bossel Ben-Moshe & Shelly Hen-Avivi & Natalia Levitin & Dror Yehezkel & Marije Oosting & Leo A. B. Joosten & Mihai G. Netea & Roi Avraham, 2019. "Predicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11257-y
    DOI: 10.1038/s41467-019-11257-y
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    Cited by:

    1. Timothy R. McCulloch & Gustavo R. Rossi & Louisa Alim & Pui Yeng Lam & Joshua K. M. Wong & Elaina Coleborn & Snehlata Kumari & Colm Keane & Andrew J. Kueh & Marco J. Herold & Christoph Wilhelm & Percy, 2024. "Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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