Learning Latent Trajectories in Developmental Time Series with Hidden-Markov Optimal Transport

Peter Halmos, Julian Gold, Xinhao Liu, Benjamin J. Raphael

Abstract: Deriving the sequence of transitions between cell types, or differentiation events, that occur during organismal development is one of the fundamental challenges in developmental biology. Single-cell and spatial sequencing of samples from different developmental timepoints provide data to investigate differentiation but inferring a sequence of differentiation events requires: (1) finding trajectories, or ancestor:descendant relationships, between cells from consecutive timepoints; (2) coarse-graining these trajectories into a differentiation map, or collection of transitions between cell types, rather than individual cells. We introduce Hidden-Markov Optimal Transport (HM-OT), an algorithm that simultaneously groups cells into cell types and learns transitions between these cell types from single-cell or spatial developmental time series. HM-OT uses low-rank optimal transport to simultaneously align samples in a time series and learn a sequence of clusterings and a differentiation map with minimal total transport cost.