iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection.

Autor: Hill BD; Department of Chemical Engineering., Zak AJ; Department of Chemical Engineering., Raja S; Department of Chemical Engineering., Bugada LF; Department of Chemical Engineering., Rizvi SM; Department of Chemical Engineering., Roslan SB; Department of Chemical Engineering., Nguyen HN; Department of Chemical Engineering., Chen J; Program in Immunology.; Department of Internal Medicine., Jiang H; Department of Biostatistics, and., Ono A; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA., Goldstein DR; Department of Internal Medicine., Wen F; Department of Chemical Engineering.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 May 30; Vol. 9 (12). Date of Electronic Publication: 2024 May 30.
DOI: 10.1172/jci.insight.172140
Abstrakt: Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult. We have developed a new analytical approach, in silico gating annotating training elucidating (iGATE), based on probabilistic support vector machine classification. By rapidly and accurately "gating" tens of millions of cells in silico into user-defined types, iGATE enabled us to track 25 canonical immune cell types in mouse lung over the course of influenza infection. Applying iGATE to study effects of host genetic background, we show that the lower survival of C57BL/6 mice compared with BALB/c was associated with a more rapid accumulation of inflammatory cell types and decreased IL-10 expression. Furthermore, we demonstrate that the most prominent effect of aging is a defective T cell response, reducing survival of aged mice. Finally, iGATE reveals that the 25 canonical immune cell types exhibited differential influenza infection susceptibility and replication permissiveness in vivo, but neither property varied with host genotype or aging. The software is available at https://github.com/UmichWenLab/iGATE.
Databáze: MEDLINE