Multiplexed high-throughput immune cell imaging reveals molecular health-associated phenotypes

Phenotypic plasticity is essential to the immune system, yet the factors that shape it are not fully understood. Here, we comprehensively analyze immune cell phenotypes including morphology across human cohorts by single-round multiplexed immunofluorescence, automated microscopy, and deep learning....

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Bibliographic Details
Published in:Science advances 2022-11, Vol.8 (44), p.eabn5631-eabn5631
Main Authors: Severin, Yannik, Hale, Benjamin D, Mena, Julien, Goslings, David, Frey, Beat M, Snijder, Berend
Format: Article
Language:English
Subjects:
Humans
Inflammation - genetics
Neural Networks, Computer
Phenotype
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Summary:Phenotypic plasticity is essential to the immune system, yet the factors that shape it are not fully understood. Here, we comprehensively analyze immune cell phenotypes including morphology across human cohorts by single-round multiplexed immunofluorescence, automated microscopy, and deep learning. Using the uncertainty of convolutional neural networks to cluster the phenotypes of eight distinct immune cell subsets, we find that the resulting maps are influenced by donor age, gender, and blood pressure, revealing distinct polarization and activation-associated phenotypes across immune cell classes. We further associate T cell morphology to transcriptional state based on their joint donor variability and validate an inflammation-associated polarized T cell morphology and an age-associated loss of mitochondria in CD4 T cells. Together, we show that immune cell phenotypes reflect both molecular and personal health information, opening new perspectives into the deep immune phenotyping of individual people in health and disease.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abn5631