A self-exciting point process to study multicellular spatial signaling patterns. Author Archit Verma, Siddhartha Jena, Danielle Isakov, Kazuhiro Aoki, Jared Toettcher, Barbara Engelhardt Publication Year 2021 Type Journal Article 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 Animals, Models, Biological, Signal Transduction, Models, Statistical, MAP Kinase Signaling System, Mice, Transgenic, Epithelial Cells, Keratinocytes, Dogs, Protein Kinase Inhibitors, Madin Darby Canine Kidney Cells, Dipeptides, Spatio-Temporal Analysis, Hydroxamic Acids, Mice, Inbred Strains Journal Proc Natl Acad Sci U S A Volume 118 Issue 32 Date Published 2021 Aug 10 ISSN Number 1091-6490 DOI 10.1073/pnas.2026123118 Alternate Journal Proc Natl Acad Sci U S A PMCID PMC8364135 PMID 34362843 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML