scShaper: an ensemble method for fast and accurate linear trajectory inference from single-cell RNA-seq data

Bioinformatics. 2022 Feb 7;38(5):1328-1335. doi: 10.1093/bioinformatics/btab831.

Abstract

Motivation: Computational models are needed to infer a representation of the cells, i.e. a trajectory, from single-cell RNA-sequencing data that model cell differentiation during a dynamic process. Although many trajectory inference methods exist, their performance varies greatly depending on the dataset and hence there is a need to establish more accurate, better generalizable methods.

Results: We introduce scShaper, a new trajectory inference method that enables accurate linear trajectory inference. The ensemble approach of scShaper generates a continuous smooth pseudotime based on a set of discrete pseudotimes. We demonstrate that scShaper is able to infer accurate trajectories for a variety of trigonometric trajectories, including many for which the commonly used principal curves method fails. A comprehensive benchmarking with state-of-the-art methods revealed that scShaper achieved superior accuracy of the cell ordering and, in particular, the differentially expressed genes. Moreover, scShaper is a fast method with few hyperparameters, making it a promising alternative to the principal curves method for linear pseudotemporal ordering.

Availability and implementation: scShaper is available as an R package at https://github.com/elolab/scshaper. The test data are available at https://doi.org/10.5281/zenodo.5734488.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Exome Sequencing
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Single-Cell Gene Expression Analysis*
  • Software*