Highlights d Fate-seq links the drug response of a single cell to its own transcriptomic profile d Fate-seq recovers variable cell decision information from unstructured variability d It identifies molecular factors causing the intrinsic resistance to cancer drugs d A TRAIL therapeutic efficacy profile is performed in HeLa cells as proof of concept

The apoptotic signaling pathway designates a set of biochemical reactions involved in programmed cell death. One of the triggering mechanisms of apoptosis is the binding of death ligands to death receptors on the cell membrane, a known stimulus for the activation of the so-called extrinsic apoptosis signaling pathway. Stimulation by death ligands results in an important variability in cell response dynamics that elicits differing fates: cell survival or cell death. To understand the hallmarks of this cell fate decision and the heterogeneity of cell response, a system of ordinary differential equations based on mass-action rate laws was implemented to represent the reactions at the receptor level and evaluate the cell dynamics in response to anticancer drugs.