Entropy-based inference of transition states and cellular trajectory for single-cell transcriptomics

Abstract The development of single-cell RNA-seq (scRNA-seq) technology allows researchers to characterize the cell types, states and transitions during dynamic biological processes at single-cell resolution. One of the critical tasks is to infer pseudo-time trajectory. However, the existence of transition cells in the intermediate state of complex biological processes poses a challenge for the trajectory inference. Here, we propose a new single-cell trajectory inference method based on transition entropy, named scTite, to identify transitional states and reconstruct cell trajectory from scRNA-seq data. Taking into account the continuity of cellular processes, we introduce a new metric called transition entropy to measure the uncertainty of a cell belonging to different cell clusters, and then identify cell states and transition cells. Specifically, we adopt different strategies to infer the trajectory for the identified cell states and transition cells, and combine them to obtain a detailed cell trajectory. For the identified cell clusters, we utilize the Wasserstein distance based on the probability distribution to calculate distance between clusters, and construct the minimum spanning tree. Meanwhile, we adopt the signaling entropy and partial correlation coefficient to determine transition paths, which contain a group of transition cells with the largest similarity. Then the transitional paths and the MST are combined to infer a refined cell trajectory. We apply scTite to four real scRNA-seq datasets and an integrated dataset, and conduct extensive performance comparison with nine existing trajectory inference methods. The experimental results demonstrate that the proposed method can reconstruct the cell trajectory more accurately than the compared algorithms. The scTite software package is available at https://github.com/dblab2022/scTite.