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- W4309151026 abstract "Abstract Cellular stimulation via factors such as cytokines followed by multiparameter single-cell measurements is a powerful approach to interrogate cellular functions. However, transforming such high-dimensional data into biological insights presents unique challenges, particularly given the extensive response heterogeneity among single cells, such as the presence of bimodal responding versus non-responding subpopulations upon stimulation. Here we present an unsupervised h igh- d imensional approach for analyzing stim ulation responses at the single cell level ( HDStIM) and apply it to evaluate how pediatric development may shape peripheral immune cell signaling states and responsiveness to stimulations in 42 subjects (age: 2 - 16). We show that in comparison to the conventional approach of assessing one marker at a time by averaging across single cells, HDStIM can effectively learn, in an unsupervised fashion, the multi-parameter signature of responding versus non-responding cells to accurately quantify responses within cell populations. HDStIM reveals that the extent of pre-stimulation/baseline activation of interferon-related and TCR signaling molecules in myeloid and T cells, respectively, increases during puberty. This suggests that puberty is marked by a heightened “tonic” activation state in these cells, perhaps to strengthen defense against pathogens during this period of human development." @default.
- W4309151026 created "2022-11-23" @default.
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- W4309151026 date "2022-11-16" @default.
- W4309151026 modified "2023-09-27" @default.
- W4309151026 title "Multiparameter stimulation mapping of signaling states in single pediatric immune cells reveals heightened tonic activation during puberty" @default.
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- W4309151026 doi "https://doi.org/10.1101/2022.11.14.516371" @default.
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