Analyses of cell-to-cell communication combining a heterogeneous deep ensemble framework and scoring approaches from single-cell RNA sequencing data

Cell-to-cell communication (CCC) plays essential roles in multicellular organisms. the identification of CCC between cancer cells themselves and one between cancer cells and normal cells in tumor microenvironment contributes to the understanding of carcinogenesis, cancer development and metastasis. CCC is usually mediated by Ligand-Receptor Interactions (LRIs). In this manuscript, we developed an LRI-mediated CCC estimation framework (LRI-EnABCLG) by incorporating LRI collection, prediction and filtering, CCC inference and visualization. First, four LRI datasets were collected. Second, LRIs were predicted by a heterogeneous deep ensemble model. Third, LRIs were filtered by combining single-cell sequencing (scRNA-seq) data. Fourth, CCC was inferred by combining the filtered LRIs and scRNA-seq data. Finally, the proposed CCC prediction framework was applied to CCC analysis in colorectal tumor tissues. Our proposed LRI-EnABCLG model obtained better LRI prediction performance. Case study demonstrated that fibroblasts was more likely to communicate with colorectal cancer cells, which was in accord with the results from iTALK (a classical CCC analysis pipeline). We anticipate that this work can contribute to diagnosis and treatment of cancers.