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

Autor: Oliver J Maclaren, Aimée Parker, Carmen Pin, Simon R Carding, Alastair J M Watson, Alexander G Fletcher, Helen M Byrne, Philip K Maini
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS Computational Biology, Vol 13, Iss 7, p e1005688 (2017)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1005688
Popis: 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.
Databáze: Directory of Open Access Journals
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