Identifying cell-to-cell variability in internalisation using flow cytometry

AP Browning, N Ansari, C Drovandi, A Johnston, MJ Simpson, AL Jenner

Preprint

Biological heterogeneity is a primary contributor to the variation observed in experiments that probe dynamical processes, such as internalisation. Given that internalisation is the primary means by which cells absorb drugs, viruses and other material, quantifying cell-to-cell variability in internalisation is of high biological interest. Yet, it is common for studies of internalisation to neglect cell-to-cell variability.

We develop a simple mathematical model of internalisation that captures the dynamical behaviour, cell-to-cell variation, and extrinsic noise introduced by flow cytometry. We calibrate our model through a novel distribution-matching approximate Bayesian computation algorithm to flow cytometry data collected from an experiment that probes the internalisation of antibody by transferrin receptors in C1R cells. Our model reproduces experimental observations, identifies cell-to-cell variability in the internalisation and recycling rates, and, importantly, provides information relating to inferential uncertainty. Given that our approach is agnostic to sample size and signal-to-noise ratio, our modelling framework is broadly applicable to identify biological variability in single-cell data from experiments that probe a range of dynamical processes.