Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments

Abstract

In-vitro chemo-sensitivity experiments are an essential step in the early stages of cancer therapy development, but existing data analysis methods suffer from problems with fitting, do not permit assessment of uncertainty, and can give misleading estimates of cell growth inhibition. We present an approach (bdChemo) based on a mechanistic model of cell division and death that permits rigorous statistical analyses of chemo-sensitivity experiment data by simultaneous estimation of cell division and apoptosis rates as functions of dose, without making strong assumptions about the shape of the dose-response curve. We demonstrate the utility of this method using a large-scale NCI-DREAM challenge dataset. We developed an R package “bdChemo” implementing this method, available at https://github.com/YiyiLiu1/bdChemo.