Analysis of variability in estimates of cell proliferation parameters for cyton-based models using CFSE-based flow cytometry data

Abstract

In this article we assess variability in cell proliferation dynamics observed for CD4+ and CD8+ T cells collected from two healthy donors. We review a recently developed class of models that incorporates the so-called “cyton model” for cell numbers into a conservation-based PDE model for cell population dynamics and describe a statistical model that relates CFSE-based flow cytometry data to such models. A parameter estimation scheme is summarized and then applied to a large body of data to assess experimental variability (variation in parameter estimates as identical experiments are replicated) and biological variability (differences in parameter estimates obtained for different donors and cell types) in the context of these models. Variability in the data obtained from replicated experiments is also discussed. The results of this study indicate that many of the cyton model parameters for describing cell proliferation can be reliably estimated using our approach; however, they also show that substantial changes to our mathematical model and/or experimental procedures may be required to ensure identifiability of the remaining cell proliferation parameters.