LISA2: Learning Complex Single-Cell Trajectory and Expression Trends

Single-cell transcriptional and epigenomics profiles have been applied in a variety of tissues and diseases for discovering new cell types, differentiation trajectories, and gene regulatory networks. Many methods such as Monocle 2/3, URD, and STREAM have been developed for tree-based trajectory building. Here, we propose a fast and flexible trajectory learning method, LISA2, for single-cell data analysis. This new method has two distinctive features: (1) LISA2 utilizes specified leaves and root to reduce the complexity for building the developmental trajectory, especially for some special cases such as rare cell populations and adjacent terminal cell states; and (2) LISA2 is applicable for both transcriptomics and epigenomics data. LISA2 visualizes complex trajectories using 3D Landmark ISOmetric feature MAPping (L-ISOMAP). We apply LISA2 to simulation and real datasets in cerebellum, diencephalon, and hematopoietic stem cells including both single-cell transcriptomics data and single-cell assay for transposase-accessible chromatin data. LISA2 is efficient in estimating single-cell trajectory and expression trends for different kinds of molecular state of cells.