Mechanistic inference of stochastic gene expression from structured single-cell data

Abstract: Single-cell gene expression measurements encode variability spanning molecular noise, cellular heterogeneity, and technical artifacts. Mechanistic models provide a principled framework to disentangle these sources and extract insight, but inferring underlying dynamics from standard sequencing count data faces fundamental limitations. Structured datasets with temporal, spatial, or multimodal features offer constraints that help resolve these ambiguities, but demand more complex models and advanced inference strategies, including machine learning techniques with associated tradeoffs. This review highlights recent progress in the judicious integration of structured single-cell data, stochastic model development, and innovative inference strategies to extract gene-level insights. These approaches lay the foundation for mechanistic understanding of regulatory networks and multicellular systems.