Journal
BIOINFORMATICS
Volume 38, Issue 12, Pages 3216-3221Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btac294
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Funding
- National Cancer Institute [U2C CA233291, U54 CA217450]
- National Institutes of Health [P01 AI139449]
- Cancer Center Support Grant [P30CA068485]
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This study developed a statistical method for examining dysregulated ligand-receptor interactions in different conditions, and successfully applied it to the study of important diseases such as COVID-19 infection and pulmonary fibrosis.
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-beta signaling from alveolar type II cells in the pathogenesis of pulmonary fibrosis.
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