SCOUT: A new algorithm for the inference of pseudo-time trajectory using single-cell data

Abstract

Single cell technology is a powerful tool to reveal intercellular heterogeneity and discover cellular developmental processes. When analyzing the complexity of cellular dynamics and variability, it is important to construct a pseudo-time trajectory using single-cell expression data to reflect the process of cellular development. Although a number of computational and statistical methods have been developed recently for single-cell analysis, more effective and efficient methods are still strongly needed. In this work we propose a new method named SCOUT for the inference of single-cell pseudo-time ordering with bifurcation trajectories. We first propose to use the fixed-radius near neighbors algorithms based on cell densities to find landmarks to represent the cell states, and employ the minimum spanning tree (MST) to determine the developmental branches. We then propose to use the projection of Apollonian circle or a weighted distance to determine the pseudo-time trajectories of single cells. The proposed algorithm is applied to one synthetic and two realistic single-cell datasets (including single-branching and multi-branching trajectories) and the cellular developmental dynamics is recovered successfully. Compared with other popular methods, numerical results show that our proposed method is able to generate more robust and accurate pseudo-time trajectories. The code of the method is implemented in Python and available at https://github.com/statway/SCOUT.

Keywords: Cell heterogeneity; Pseudo-time trajectory; Single-cell transcriptomics.