Dysregulated ligand-receptor interactions from single-cell transcriptomics

Bioinformatics. 2022 Jun 13;38(12):3216-3221. doi: 10.1093/bioinformatics/btac294.

Abstract

Motivation: Intracellular communication is crucial to many biological processes, such as differentiation, development, homeostasis and inflammation. Single-cell transcriptomics provides an unprecedented opportunity for studying cell-cell communications mediated by ligand-receptor interactions. Although computational methods have been developed to infer cell type-specific ligand-receptor interactions from one single-cell transcriptomics profile, there is lack of approaches considering ligand and receptor simultaneously to identifying dysregulated interactions across conditions from multiple single-cell profiles.

Results: We developed scLR, a statistical method for examining dysregulated ligand-receptor interactions between two conditions. scLR models the distribution of the product of ligands and receptors expressions and accounts for inter-sample variances and small sample sizes. scLR achieved high sensitivity and specificity in simulation studies. scLR revealed important cytokine signaling between macrophages and proliferating T cells during severe acute COVID-19 infection, and activated TGF-β signaling from alveolar type II cells in the pathogenesis of pulmonary fibrosis.

Availability and implementation: scLR is freely available at https://github.com/cyhsuTN/scLR.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19*
  • Humans
  • Ligands
  • Sample Size
  • Transcriptome*

Substances

  • Ligands