Quantification and statistical comparison of cell-state transition kinetics using a parametric failure-based model

Abstract

Successful development of multicellular organisms requires cells to transition between states with precise timing. Distinct cell states are often understood as being maintained by stabilizing regulatory networks, such that a complete cell-state transition requires network rewiring through partial dismantling of the current state and concurrent reconfiguration into a new one. Empirically, these transitions are often investigated by quantifying the gain or loss of expression of a small number of state-specific markers, frequently a single proxy. A general quantitative framework for comparing the kinetics of such transitions across experimental conditions is lacking. Here, we show that the delayed Weibull distribution provides a natural description of cell-state transition kinetics when transition is viewed as the cumulative consequence of many molecular events, whose timing may vary between cells and conditions, analogous to system failure in reliability theory. This formulation yields a compact model with interpretable parameters describing the delay before transition onset, the characteristic timescale of transition, the temporal form of the transition hazard, and the fraction of cells competent to respond. Together, this framework provides a practical and interpretable approach for quantifying the kinetics of cell-state transitions and how they are altered by perturbation.