@article{1c5b8567ff0b4e3a940dfcca6ae224b0,
title = "A self-exciting point process to study multicellular spatial signaling patterns",
abstract = "Multicellular organisms rely on spatial signaling among cells to drive their organization, development, and response to stimuli. Several models have been proposed to capture the behavior of spatial signaling in multicellular systems, but existing approaches fail to capture both the autonomous behavior of single cells and the interactions of a cell with its neighbors simultaneously. We propose a spatiotemporal model of dynamic cell signaling based on Hawkes processes-self-exciting point processes-that model the signaling processes within a cell and spatial couplings between cells. With this cellular point process (CPP), we capture both the single-cell pathway activation rate and the magnitude and duration of signaling between cells relative to their spatial location. Furthermore, our model captures tissues composed of heterogeneous cell types with different bursting rates and signaling behaviors across multiple signaling proteins. We apply our model to epithelial cell systems that exhibit a range of autonomous and spatial signaling behaviors basally and under pharmacological exposure. Our model identifies known drug-induced signaling deficits, characterizes signaling changes across a wound front, and generalizes to multichannel observations.",
keywords = "Cell signaling, Hawkes process, Keratinocytes, Kinase networks, Point process",
author = "Archit Verma and Jena, {Siddhartha G.} and Isakov, {Danielle R.} and Kazuhiro Aoki and Toettcher, {Jared E.} and Engelhardt, {Barbara E.}",
note = "Funding Information: ACKNOWLEDGMENTS. We would like to thank Alexander Goglia for kindly providing data and annotations from his experimental drug screen (6). S.G.J. was supported by NIH Ruth Kirschstein fellowship F31AR075398 and NIH Training Grant T32GM007388. A.V. and B.E.E. were supported by the NIH National Heart, Lung, and Blood Institute R01 HL133218 and NSF CAREER AWD1005627. J.E.T. was supported by NIH Grant DP2EB024247 and NSF CAREER Award 1750663. B.E.E. and J.E.T. gratefully acknowledge financial support from the Schmidt DataX Fund at Princeton University made possible through a major gift from the Schmidt Futures Foundation. Funding Information: We would like to thank Alexander Goglia for kindly providing data and annotations from his experimental drug screen (6). S.G.J. was supported by NIH Ruth Kirschstein fellowship F31AR075398 and NIH Training Grant T32GM007388. A.V. and B.E.E. were supported by the NIH National Heart, Lung, and Blood Institute R01 HL133218 and NSF CAREER AWD1005627. J.E.T. was supported by NIH Grant DP2EB024247 and NSF CAREER Award 1750663. B.E.E. and J.E.T. gratefully acknowledge financial support from the Schmidt DataX Fund at Princeton University made possible through a major gift from the Schmidt Futures Foundation. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = aug,
day = "10",
doi = "10.1073/pnas.2026123118",
language = "English (US)",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "32",
}