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Fractional response analysis reveals logarithmic cytokine responses in cellular populations

Karol Nienałtowski, Rachel E. Rigby, Jarosław Walczak, Karolina E. Zakrzewska, Jan Rehwinkel, Michał Komorowski
doi: https://doi.org/10.1101/2020.12.08.413468
Karol Nienałtowski
1Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland
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Rachel E. Rigby
2Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Jarosław Walczak
1Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland
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Karolina E. Zakrzewska
1Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland
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Jan Rehwinkel
2Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Michał Komorowski
1Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland
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  • For correspondence: m.komorowski@sysbiosig.org
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ABSTRACT

Although we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose-response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, uncovers otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 09, 2020.
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Fractional response analysis reveals logarithmic cytokine responses in cellular populations
Karol Nienałtowski, Rachel E. Rigby, Jarosław Walczak, Karolina E. Zakrzewska, Jan Rehwinkel, Michał Komorowski
bioRxiv 2020.12.08.413468; doi: https://doi.org/10.1101/2020.12.08.413468
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Fractional response analysis reveals logarithmic cytokine responses in cellular populations
Karol Nienałtowski, Rachel E. Rigby, Jarosław Walczak, Karolina E. Zakrzewska, Jan Rehwinkel, Michał Komorowski
bioRxiv 2020.12.08.413468; doi: https://doi.org/10.1101/2020.12.08.413468

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