Deciphering ligand-receptor-mediated intercellular communication based on ensemble deep learning and the joint...

Cell-cell communication in a tumor microenvironment is vital to tumorigenesis, tumor progression and therapy. Intercellular communication inference helps understand molecular mechanisms of tumor growth, progression and metastasis.

Focusing on ligand-receptor co-expressions, in this study, we developed an ensemble deep learning framework, CellComNet, to decipher ligand-receptor-mediated cell-cell communication from single-cell transcriptomic data. First, credible LRIs are captured by integrating data arrangement, feature extraction, dimension reduction, and LRI classification based on an ensemble of heterogeneous Newton boosting machine and deep neural network. Next, known and identified LRIs are screened based on single-cell RNA sequencing (scRNA-seq) data in certain tissues. Finally, cell-cell communication is inferred by incorporating scRNA-seq data, the screened LRIs, a joint scoring strategy that combines expression thresholding and expression product of ligands and receptors.

The proposed CellComNet framework was compared with four competing protein-protein interaction prediction models (PIPR, XGBoost, DNNXGB, and OR-RCNN) and obtained the best AUCs and AUPRs on four LRI datasets, elucidating the optimal LRI classification ability. CellComNet was further applied to analyze intercellular communication in human melanoma and head and neck squamous cell carcinoma (HNSCC) tissues. The results demonstrate that cancer-associated fibroblasts highly communicate with melanoma cells and endothelial cells strong communicate with HNSCC cells.

The proposed CellComNet framework efficiently identified credible LRIs and significantly improved cell-cell communication inference performance. We anticipate that CellComNet can contribute to anticancer drug design and tumor-targeted therapy.