CellGAT: A GAT-Based Method for Constructing a Cell Communication Network Integrating Multiomics Information

The growth, development, and differentiation of multicellular organisms are primarily driven by intercellular communication, which coordinates the activities of diverse cell types. This cell-to-cell signaling is typically mediated by various types of protein–protein interactions, including ligand–receptor; receptor–receptor, and extracellular matrix–receptor interactions. Currently, computational methods for inferring ligand–receptor communication primarily depend on gene expression data of ligand–receptor pairs and spatial information of cells. Some approaches integrate protein complexes; transcription factors; or pathway information to construct cell communication networks. However, few methods consider the critical role of protein–protein interactions (PPIs) in intercellular communication networks, especially when predicting communication between different cell types in the absence of cell type information. These methods often rely on ligand–receptor pairs that lack PPI evidence, potentially compromising the accuracy of their predictions. To address this issue, we propose CellGAT, a framework that infers intercellular communication by integrating gene expression data of ligand–receptor pairs, PPI information, protein complex data, and experimentally validated pathway information. CellGAT not only builds a priori models but also uses node embedding algorithms and graph attention networks to build cell communication networks based on scRNA-seq (single-cell RNA sequencing) datasets and includes a built-in cell clustering algorithm. Through comparisons with various methods, CellGAT accurately predicts cell–cell communication (CCC) and analyzes its impact on downstream pathways; neighboring cells; and drug interventions.