Clustering and visualization of single-cell RNA-seq data using path metrics

PLoS Comput Biol. 2024 May 29;20(5):e1012014. doi: 10.1371/journal.pcbi.1012014. eCollection 2024 May.

Abstract

Recent advances in single-cell technologies have enabled high-resolution characterization of tissue and cancer compositions. Although numerous tools for dimension reduction and clustering are available for single-cell data analyses, these methods often fail to simultaneously preserve local cluster structure and global data geometry. To address these challenges, we developed a novel analyses framework, Single-Cell Path Metrics Profiling (scPMP), using power-weighted path metrics, which measure distances between cells in a data-driven way. Unlike Euclidean distance and other commonly used distance metrics, path metrics are density sensitive and respect the underlying data geometry. By combining path metrics with multidimensional scaling, a low dimensional embedding of the data is obtained which preserves both the global data geometry and cluster structure. We evaluate the method both for clustering quality and geometric fidelity, and it outperforms current scRNAseq clustering algorithms on a wide range of benchmarking data sets.

MeSH terms

  • Algorithms*
  • Cluster Analysis
  • Computational Biology* / methods
  • Gene Expression Profiling / methods
  • Gene Expression Profiling / statistics & numerical data
  • Humans
  • RNA-Seq / methods
  • RNA-Seq / statistics & numerical data
  • Sequence Analysis, RNA / methods
  • Sequence Analysis, RNA / statistics & numerical data
  • Single-Cell Analysis* / methods
  • Single-Cell Analysis* / statistics & numerical data
  • Single-Cell Gene Expression Analysis