CellStream: Dynamical Optimal Transport Informed Embeddings for Reconstructing Cellular Trajectories from Snapshots Data

Abstract: Single-cell RNA sequencing (scRNA-seq), especially temporally resolved datasets, enables genome-wide profiling of gene expression dynamics at single-cell resolution across discrete time points. However, current technologies provide only sparse, static snapshots of cell states and are inherently influenced by technical noise, complicating the inference and representation of continuous transcriptional dynamics. Although embedding methods can reduce dimensionality and mitigate technical noise, the majority of existing approaches typically treat trajectory inference separately from embedding construction, often neglecting temporal structure. To address this challenge, here we introduce CellStream, a novel deep learning framework that jointly learns embedding and cellular dynamics from single-cell snapshot data by integrating an autoencoder with unbalanced dynamical optimal transport. Compared to existing methods, CellStream generates dynamics-informed embeddings that robustly capture temporal developmental processes while maintaining high consistency with the underlying data manifold. We demonstrate CellStream's effectiveness on both simulated datasets and real scRNA-seq data, including spatial transcriptomics. Our experiments indicate significant quantitative improvements over state-of-the-art methods in representing cellular trajectories with enhanced temporal coherence and reduced noise sensitivity. Overall, CellStream provides a new tool for learning and representing continuous streams from the noisy, static snapshots of single-cell gene expression.