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

Autor: Marije Oosting, Leo A. B. Joosten, Mihai G. Netea, Shelly Hen-Avivi, Roi Avraham, Natalia Levitin, Dror Yehezkel, Noa Bossel Ben-Moshe
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cell type
Science
Cell
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Predictive medicine
General Physics and Astronomy
02 engineering and technology
Disease
Computational biology
Biology
Article
General Biochemistry
Genetics and Molecular Biology

Cohort Studies
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Immune system
Predictive Value of Tests
Salmonella
medicine
Cluster Analysis
Humans
lcsh:Science
Pathogen
Cells
Cultured

Multidisciplinary
Sequence Analysis
RNA

Gene Expression Profiling
High-Throughput Nucleotide Sequencing
RNA
RNA sequencing
General Chemistry
021001 nanoscience & nanotechnology
Bacterial host response
3. Good health
030104 developmental biology
medicine.anatomical_structure
Immune System
Host-Pathogen Interactions
Salmonella Infections
Natural Killer T-Cells
lcsh:Q
Bacterial infection
Single-Cell Analysis
0210 nano-technology
Algorithms
Ex vivo
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019)
Nature Communications, 10
Nature Communications
ISSN: 2041-1723
Popis: 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.
Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Here, Avraham and colleagues present a deconvolution algorithm that uses single-cell RNA and bulk RNA sequencing measurements of pathogen-infected cells to predict disease risk outcomes.
Databáze: OpenAIRE