Abstract
The role of cell-cell communications (CCCs) is increasingly recognized as being important to differentiation, invasion, metastasis, and drug resistance in tumoral tissues. Developing CCC inference methods using traditional experimental methods are time-consuming, labor-intensive, cannot handle large amounts of data. To facilitate inference of CCCs, we proposed a computational framework, called CellMsg, which involves two primary steps: identifying ligand-receptor interactions (LRIs) and measuring the strength of LRIs-mediated CCCs. Specifically, CellMsg first identifies high-confident LRIs based on multimodal features of ligands and receptors and graph convolutional networks. Then, CellMsg measures the strength of intercellular communication by combining the identified LRIs and single-cell RNA-seq data using a three-point estimation method. Performance evaluation on four benchmark LRI datasets by five-fold cross validation demonstrated that CellMsg accurately captured the relationships between ligands and receptors, resulting in the identification of high-confident LRIs. Compared with other methods of identifying LRIs, CellMsg has better prediction performance and robustness. Furthermore, the LRIs identified by CellMsg were successfully validated through molecular docking. Finally, we examined the overlap of LRIs between CellMsg and five other classical CCC databases, as well as the intercellular crosstalk among seven cell types within a human melanoma tissue. In summary, CellMsg establishes a complete, reliable, and well-organized LRI database and an effective CCC strength evaluation method for each single-cell RNA-seq data. It provides a computational tool allowing researchers to decipher intercellular communications. CellMsg is freely available at https://github.com/pengsl-lab/CellMsg.