Dysregulated ligand–receptor interactions from single-cell transcriptomics

Abstract

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.