BLTSA: pseudotime prediction for single cells by branched local tangent space alignment

Abstract

Motivation: The development of single-cell RNA sequencing (scRNA-seq) technology makes it possible to study the cellular dynamic processes such as cell cycle and cell differentiation. Due to the difficulties in generating genuine time-series scRNA-seq data, it is of great importance to computationally infer the pseudotime of the cells along differentiation trajectory based on their gene expression patterns. The existing pseudotime prediction methods often suffer from the high level noise of single-cell data, thus it is still necessary to study the single-cell trajectory inference methods. Results: In this study, we propose a branched local tangent space alignment (BLTSA) method to infer single-cell pseudotime for multi-furcation trajectories. By assuming that single cells are sampled from a low-dimensional self-intersecting manifold, BLTSA first identifies the tip and branching cells in the trajectory based on cells’ local Euclidean neighborhoods. Local coordinates within the tangent spaces are then determined by each cell’s local neighborhood after clustering all the cells to different branches iteratively. The global coordinates for all the single cells are finally obtained by aligning the local coordinates based on the tangent spaces. We evaluate the performance of BLTSA on four simulation datasets and five real datasets. The experimental results show that BLTSA has obvious advantages over other comparison methods.