A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium

Maclaren, Oliver J., Parker, Aimée, Pin, Carmen, Carding, Simon R., Watson, Alastair J. M. ORCID: https://orcid.org/0000-0003-3326-0426, Fletcher, Alexander G., Byrne, Helen M. and Maini, Phillip K. (2017) A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium. PLoS Computational Biology, 13 (7). ISSN 1553-734X

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Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions—uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
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Depositing User: Pure Connector
Date Deposited: 26 Jul 2017 05:04
Last Modified: 20 Dec 2022 08:58
URI: https://ueaeprints.uea.ac.uk/id/eprint/64268
DOI: 10.1371/journal.pcbi.1005688


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