Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy.

Autor:	Barone SM; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Paul AGA; Allergy Division, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA., Muehling LM; Allergy Division, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA., Lannigan JA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA., Kwok WW; Benaroya Research Institute at Virginia Mason, Seattle, WA, USA., Turner RB; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA., Woodfolk JA; Allergy Division, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA., Irish JM; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2020 Nov 04. Date of Electronic Publication: 2020 Nov 04.
DOI:	10.1101/2020.07.31.190454
Abstrakt:	For an emerging disease like COVID-19, systems immunology tools may quickly identify and quantitatively characterize cells associated with disease progression or clinical response. With repeated sampling, immune monitoring creates a real-time portrait of the cells reacting to a novel virus before disease specific knowledge and tools are established. However, single cell analysis tools can struggle to reveal rare cells that are under 0.1% of the population. Here, the machine learning workflow Tracking Responders Expanding (T-REX) was created to identify changes in both very rare and common cells in diverse human immune monitoring settings. T-REX identified cells that were highly similar in phenotype and localized to hotspots of significant change during rhinovirus and SARS-CoV-2 infections. Specialized reagents used to detect the rhinovirus-specific CD4 + cells, MHCII tetramers, were not used during unsupervised analysis and instead 'left out' to serve as a test of whether T-REX identified biologically significant cells. In the rhinovirus challenge study, T-REX identified virus-specific CD4 + T cells based on these cells being a distinct phenotype that expanded by ≥95% following infection. T-REX successfully identified hotspots containing virus-specific T cells using pairs of samples comparing Day 7 of infection to samples taken either prior to infection (Day 0) or after clearing the infection (Day 28). Mapping pairwise comparisons in samples according to both the direction and degree of change provided a framework to compare systems level immune changes during infectious disease or therapy response. This revealed that the magnitude and direction of systemic immune change in some COVID-19 patients was comparable to that of blast crisis acute myeloid leukemia patients undergoing induction chemotherapy and characterized the identity of the immune cells that changed the most. Other COVID-19 patients instead matched an immune trajectory like that of individuals with rhinovirus infection or melanoma patients receiving checkpoint inhibitor therapy. T-REX analysis of paired blood samples provides an approach to rapidly identify and characterize mechanistically significant cells and to place emerging diseases into a systems immunology context.
Databáze:	MEDLINE
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