Quantifying uncertainty in parameter estimates for stochastic models of collective cell spreading using approximate Bayesian computation

Mathematical Biosciences
Brenda N VoMatthew J Simpson

Abstract

Wound healing and tumour growth involve collective cell spreading, which is driven by individual motility and proliferation events within a population of cells. Mathematical models are often used to interpret experimental data and to estimate the parameters so that predictions can be made. Existing methods for parameter estimation typically assume that these parameters are constants and often ignore any uncertainty in the estimated values. We use approximate Bayesian computation (ABC) to estimate the cell diffusivity, D, and the cell proliferation rate, λ, from a discrete model of collective cell spreading, and we quantify the uncertainty associated with these estimates using Bayesian inference. We use a detailed experimental data set describing the collective cell spreading of 3T3 fibroblast cells. The ABC analysis is conducted for different combinations of initial cell densities and experimental times in two separate scenarios: (i) where collective cell spreading is driven by cell motility alone, and (ii) where collective cell spreading is driven by combined cell motility and cell proliferation. We find that D can be estimated precisely, with a small coefficient of variation (CV) of 2-6%. Our results indicate that D appears t...Continue Reading

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Citations

Apr 18, 2016·Journal of Theoretical Biology·Stuart T JohnstonMatthew J Simpson
Dec 8, 2015·PLoS Computational Biology·Brenda N VoGraeme J Pettet
Feb 3, 2018·Journal of Mathematical Biology·Ben LambertHelen M Byrne
Oct 16, 2019·Proceedings. Mathematical, Physical, and Engineering Sciences·Maud El-HachemMatthew J Simpson
Mar 4, 2020·Journal of the Royal Society, Interface·Matthew J SimpsonOliver J Maclaren
Mar 25, 2017·Bulletin of Mathematical Biology·Wang JinMatthew J Simpson
Jul 1, 2017·Bulletin of Mathematical Biology·Alexander P BrowningMatthew J Simpson
Sep 19, 2018·Royal Society Open Science·Andrew ParkerRuth E Baker
Apr 9, 2019·Journal of the Royal Society, Interface·David J WarneMatthew J Simpson
Jun 27, 2017·NPJ Systems Biology and Applications·Robert J H RossC A Yates

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