Understanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. Researchers from the University of California, Irvine constructed a database of interactions among ligands, receptors and their cofactors that accurately represent known heteromeric molecular complexes. They then developed CellChat, a tool that is able to quantitatively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applying CellChat to mouse and human skin datasets shows its ability to extract complex signaling patterns. This versatile and easy-to-use toolkit CellChat and a web-based Explorer will help discover novel intercellular communications and build cell-cell communication atlases in diverse tissues.
Overview of CellChat
a Overview of the ligand-receptor interaction database. CellChatDB takes into account known composition of the ligand-receptor complexes, including complexes with multimeric ligands and receptors, as well as several cofactor types: soluble agonists, antagonists, co-stimulatory and co-inhibitory membrane-bound receptors. CellChatDB contains 2021 validated interactions, including 60% of secreting interactions. In addition, 48% of the interactions involve heteromeric molecular complexes. b CellChat either requires user assigned cell labels as input or automatically groups cells based on the low-dimensional data representation supplied as input. c CellChat models the communication probability and identifies significant communications. d CellChat offers several visualization outputs for different analytical tasks. Different colors in the hierarchy plot and circle plot represent different cell groups. Colors in the bubble plot are proportional to the communication probability, where dark and yellow colors correspond to the smallest and largest values. e CellChat quantitatively measures networks through approaches from graph theory, pattern recognition and manifold learning, to better facilitate the interpretation of intercellular communication networks and the identification of design principles. In addition to analyzing individual dataset, CellChat also delineates signaling changes across different contexts, such as different developmental stages and biological conditions.
Availability – http://www.cellchat.org/