FateLimit quantifies the prediction horizon of cell fate

Authors:
Preprint
Publisher website
Google Scholar
Abstract
Single-cell technologies have enabled increasingly detailed reconstruction of developmental trajectories, yet a fundamental question remains unresolved: when does future cellular identity become predictable from a cell’s current molecular state? Existing approaches infer lineage relationships, transition probabilities or future transcriptional dynamics, but do not directly quantify the emergence of fate predictability during cellular state transitions. Here we present FateLimit, an information-theoretic framework for measuring the temporal dynamics of cell-fate predictability from single-cell omics data. FateLimit combines probabilistic fate assignment, fate entropy and mutual information to quantify how information about future cellular outcomes is encoded in present molecular states. We introduce two quantitative descriptors: the Fate Information Half-Life (FIHL), which measures the characteristic timescale of fate-information dynamics, and the Prediction Horizon (PH), defined as the earliest developmental stage at which observed fate predictability exceeds the 95th percentile of a permutation-derived null distribution. We applied FateLimit across developmental, lineage-tracing and reprogramming systems, including pancreatic endocrinogenesis, CellTag reprogramming, human hematopoiesis and zebrafish embryogenesis. Across all datasets, FateLimit identified significant fate information and reproducible prediction horizons that were robust to cell-state representation, lineage structure and biological context. Comparative analysis revealed that prediction horizons differ substantially among cellular lineages, indicating that distinct developmental programs acquire predictive information at different rates. FateLimit establishes a general framework for quantifying the predictability of future cellular identity from present molecular states. By transforming developmental trajectories into predictability landscapes, FateLimit enables systematic comparison of commitment dynamics across biological systems and establishes prediction horizons as a quantitative measure of cell-fate determination.
Funding Information
  • Korea Health Industry Development Institute (RS-2025-25456722)
  • Ministry of Education (MOE) and the Seoul Metropolitan Government (2026-RISE-01-022-05)

This publication has 66 references indexed in Scilit: