Autoencoder and Optimal Transport to Infer Single-Cell Trajectories of Biological Processes

Although we can increasingly image and measure biological processes at single-cell resolution, most assays can only take snapshots from a population of cells in time. Here we describe ImageAEOT , which combines an A uto E ncoder, to map single-cell Image s from different cell populations to a common latent space, with the framework of O ptimal T ransport to infer cellular trajectories. As a proof-of-concept, we apply ImageAEOT to nuclear and chromatin images during the activation of fibroblasts by tumor cells in engineered 3D tissues. We further validate ImageAEOT on chromatin images of various breast cancer cell lines and human tissue samples, thereby linking alterations in chromatin condensation patterns to different stages of tumor progression. Importantly, ImageAEOT can infer the trajectory of a particular cell from one snapshot in time and identify the changing features to provide early biomarkers for developmental and disease progression.