MultistageOT: Multistage optimal transport infers trajectories from a snapshot of single-cell data

Single-cell RNA-sequencing captures a temporal slice, or a snapshot, of a cell differentiation process. A major bioinformatical challenge is the inference of differentiation trajectories from a single snapshot, and methods that account for outlier cells that are unrelated to the differentiation process have yet to be established. We present MultistageOT: a Multistage Optimal Transport-based framework for trajectory inference in a snapshot (https://github.com/dahlinlab/MultistageOT). Application of optimal transport has proven successful for many single-cell tasks, but classical bimarginal optimal transport for trajectory inference fails to model temporal progression in a snapshot. Representing a novel generalization of optimal transport, MultistageOT addresses this major limitation by introducing a temporal dimension, allowing for high resolution modeling of intermediate differentiation stages. We challenge MultistageOT with snapshot data of cell differentiation, demonstrating effectiveness in pseudotime ordering, detection of outliers, and significantly improved fate prediction accuracy over state-of-the-art.