scRL: Utilizing Reinforcement Learning to Evaluate Fate Decisions in Single-Cell Data

Single-cell RNA sequencing now profiles whole transcriptomes for hundreds of thousands of cells, yet existing trajectory-inference tools rarely pinpoint where and when fate decisions are made. We present single-cell reinforcement learning (scRL), an actor-critic framework that recasts differentiation as a sequential decision process on an interpretable latent manifold derived with Latent Dirichlet Allocation. The critic learns state-value functions that quantify fate intensity for each cell, while the actor traces optimal developmental routes across the manifold. Benchmarks on hematopoiesis, mouse endocrinogenesis, acute myeloid leukemia, and gene-knockout and irradiation datasets show that scRL surpasses fifteen state-of-the-art methods in five independent evaluation dimensions, recovering early decision states that precede overt lineage commitment and revealing regulators such as <i>Dapp1</i>. Beyond fate decisions, the same framework produces competitive measures of lineage-contribution intensity without requiring ground-truth probabilities, providing a unified and extensible approach for decoding developmental logic from single-cell data.