Gene-Chronos: parameter-efficient developmental time inference using a pretrained single-cell foundation model.

Abstract

Large-scale single-cell and spatial transcriptomic atlases enable the study of developmental processes at high resolution. However, most datasets capture only static snapshots of cells, making it difficult to infer continuous biological time from transcriptomic profiles. Existing temporal inference methods often show limited robustness across heterogeneous datasets, and recent single-cell foundation models, although powerful for representation learning, are not designed to capture continuous temporal relationships. We present Gene-Chronos, a parameter-efficient framework for developmental time inference built on a frozen pretrained Geneformer backbone. The model introduces learnable temporal prompt tokens and a temporal contrastive objective to extract time-informative signals and encourage temporally coherent organization of cell representations. Across multiple benchmark datasets spanning diverse species and developmental stages, Gene-Chronos outperforms existing approaches and demonstrates strong generalization to previously unseen samples. Attention-based analyses further identify genes associated with developmental progression, providing interpretable insights into temporal gene expression dynamics.