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Choosing an appropriate modelling framework for analysing multispecies co-culture cell biology experiments

Deborah C Markham, Matthew J Simpson, View ORCID ProfileRuth E Baker
doi: https://doi.org/10.1101/008318
Deborah C Markham
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Radcliffe Observatory Quarter, Oxford OX2 6GG, UK. E-mail: .
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  • For correspondence: ruth.baker@maths.ox.ac.uk
Matthew J Simpson
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Ruth E Baker
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Abstract

In vitro cell biology assays play a crucial role in informing our understanding of the migratory, proliferative and invasive properties of many cell types in different biological contexts. While mono-culture assays involve the study of a population of cells composed of a single cell type, co-culture assays study a population of cells composed of multiple cell types (or subpopulations of cells). Such co-culture assays can provide more realistic insights into many biological processes including tissue repair, tissue regeneration and malignant spreading. Typically, system parameters, such as motility and proliferation rates, are estimated by calibrating a mathematical or computational model to the observed experimental data. However, parameter estimates can be highly sensitive to the choice of model and modelling framework. This observation motivates us to consider the fundamental question of how we can best choose a model to facilitate accurate parameter estimation for a particular assay. In this work we describe three mathematical models of mono-culture and co-culture assays that include different levels of spatial detail. We study various spatial summary statistics to explore if they can be used to distinguish between the suitability of each model over a range of parameter space. Our results for mono-culture experiments are promising, in that we suggest two spatial statistics that can be used to direct model choice. However, co-culture experiments are far more challenging: we show that these same spatial statistics which provide useful insight into mono-culture systems are insufficient for co-culture systems. Therefore, we conclude that great care ought to be exercised when estimating the parameters of co-culture assays.

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Posted December 02, 2014.
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Choosing an appropriate modelling framework for analysing multispecies co-culture cell biology experiments
Deborah C Markham, Matthew J Simpson, Ruth E Baker
bioRxiv 008318; doi: https://doi.org/10.1101/008318
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Choosing an appropriate modelling framework for analysing multispecies co-culture cell biology experiments
Deborah C Markham, Matthew J Simpson, Ruth E Baker
bioRxiv 008318; doi: https://doi.org/10.1101/008318

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