Identifying cell-to-cell variability using mathematical and statistical modelling

Cell-to-cell variability is often a primary source of variability in experimental data. Yet, it is common for mathematical analysis of biological systems to neglect biological variability by assuming that model parameters remain fixed between measurements. In this two-part talk, I present new mathematical and statistical tools to identify cell-to-cell variability from experimental data, based on mathematical models with random parameters. First, I identify variability in the internalisation of material by cells using approximate Bayesian computation and noisy flow cytometry measurements from several million cells. Second, I develop a computationally efficient method for inference and identifiability analysis of random parameter models based on an approximate moment-matched solution constructed through a multivariate Taylor expansion. Overall, I show how analysis of random parameter models can provide more precise parameter estimates and more accurate predictions with minimal additional computational cost compared to traditional modelling approaches.