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Andrew Parker

Publications and source records attributed to Andrew Parker.

2 recordsLinked to original sources

Using approximate Bayesian computation to quantify cell-cell adhesion parameters in a cell migratory process

In this work we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell-cell interactions. This is important as cell-cell interactions, such as adhesion and repulsion, have been shown to play an important role in cell migration. Initially, we demonstrate with a model of an ideal experiment that we are able to identify model parameters for agent motility and adhesion, given we choose appropriate summary statistics. Following this, we replace our model of an ideal experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental repeats. The results presented in this work therefore describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, the results presented in this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell-cell adhesion or repulsion are known to play a significant role.

Systems Biology

Incorporating pushing in exclusion process models of cell migration

The macroscale movement behaviour of a wide range of isolated migrating cells has been well characterised experimentally. Recently, attention has turned to understanding the behaviour of cells in crowded environments. In such scenarios it is possible for cells to interact mechanistically, inducing neighbouring cells to move in order to make room for their own movements or progeny. Although the behaviour of interacting cells has been modelled extensively through volume-exclusion processes, no models, thus far, have explicitly accounted for the ability of cells to actively displace each other.\n\nIn this work we consider both on and off-lattice volume-exclusion position-jump processes in which cells are explicitly allowed to induce movements in their near neighbours in order to create space for themselves (which we refer to as pushing). From these simple individual-level representations we derive continuum partial differential equations for the average occupancy of the domain. We find that, for limited amounts of pushing, the comparison between the averaged individual-level simulations and the population-level model is nearly as good as in the scenario without pushing but, that for larger and more complicated pushing events the assumptions used to derive the population-level model begin to break down. Interestingly, we find that, in the on-lattice case, the diffusion coefficient of the population-level model is increased by pushing, whereas, for the particular off-lattice model that we investigate, the diffusion coefficient is reduced. We conclude therefore, that it is important to consider carefully the appropriate individual-level model to use when representing complex cell-cell interactions such as pushing.

Systems Biology