Identifying potential ligand-receptor interactions based on gradient boosted neural network and interpretable boosting machine for intercellular communication analysis.

Cell-cell communication is essential to many key biological processes. Intercellular communication is generally mediated by ligand-receptor interactions (LRIs). Thus, building a comprehensive and high-quality LRI resource can significantly improve intercellular communication analysis. Meantime, due to lack of a "gold standard" dataset, it remains a challenge to evaluate LRI-mediated intercellular communication results. Here, we introduce CellGiQ, a high-confident LRI prediction framework for intercellular communication analysis. Highly confident LRIs are first inferred by LRI feature extraction with BioTriangle, LRI selection using LightGBM, and LRI classification based on ensemble of gradient boosted neural network and interpretable boosting machine. Subsequently, known and identified high-confident LRIs are filtered by combining single-cell RNA sequencing (scRNA-seq) data and further applied to intercellular communication inference through a quartile scoring strategy. To validation the predictions, CellGiQ exploited several evaluation strategies: using AUC and AUPR, it surpassed six competing LRI prediction models on four LRI datasets; through Venn diagrams and molecular docking, its predicted LRIs were validated by five other popular intercellular communication inference methods; based on the overlapping LRIs, it computed high Jaccard index with six other state-of-the-art intercellular communication prediction tools within human HNSCC tissues; by comparing with classical models and literature retrieve, its inferred HNSCC-related intercellular communication results was further validated. The novelty of this study is to identify high-confident LRIs based on machine learning as well as design several LRI validation ways, providing reference for computational LRI prediction. CellGiQ provides an open-source and useful tool to decompose LRI-mediated intercellular communication at single cell resolution. CellGiQ is freely available at https://github.com/plhhnu/CellGiQ.