Towards a mathematical theory of trajectory inference
This work addresses trajectory inference for single-cell RNA-sequencing analysis, which is incremental as it builds on existing optimal transport methods.
The authors tackled the problem of inferring trajectories of stochastic processes from samples of temporal marginals, particularly in single-cell RNA-sequencing data where cell trajectories cannot be directly tracked, and they developed an efficient algorithm (gWOT) that yields good reconstructions on synthetic and real datasets.
We devise a theoretical framework and a numerical method to infer trajectories of a stochastic process from samples of its temporal marginals. This problem arises in the analysis of single cell RNA-sequencing data, which provide high dimensional measurements of cell states but cannot track the trajectories of the cells over time. We prove that for a class of stochastic processes it is possible to recover the ground truth trajectories from limited samples of the temporal marginals at each time-point, and provide an efficient algorithm to do so in practice. The method we develop, Global Waddington-OT (gWOT), boils down to a smooth convex optimization problem posed globally over all time-points involving entropy-regularized optimal transport. We demonstrate that this problem can be solved efficiently in practice and yields good reconstructions, as we show on several synthetic and real datasets.