Graph neural networks for single-cell omics data: a review of approaches and applications

Rapid advancement of sequencing technologies now allows for the utilization of precise signals at single-cell resolution in various omics studies. However, the massive volume, ultra-high dimensionality, and high sparsity nature of single-cell data have introduced substantial difficulties to traditional computational methods. The intricate non-Euclidean networks of intracellular and intercellular signaling molecules within single-cell datasets, coupled with the complex, multimodal structures arising from multi-omics joint analysis, pose significant challenges to conventional deep learning operations reliant on Euclidean geometries. Graph neural networks (GNNs) have extended deep learning to non-Euclidean data, allowing cells and their features in single-cell datasets to be modeled as nodes within a graph structure. GNNs have been successfully applied across a broad range of tasks in single-cell data analysis. In this survey, we systematically review 107 successful applications of GNNs and their six variants in various single-cell omics tasks. We begin by outlining the fundamental principles of GNNs and their six variants, followed by a systematic review of GNN-based models applied in single-cell epigenomics, transcriptomics, spatial transcriptomics, proteomics, and multi-omics. In each section dedicated to a specific omics type, we have summarized the publicly available single-cell datasets commonly utilized in the articles reviewed in that section, totaling 77 datasets. Finally, we summarize the potential shortcomings of current research and explore directions for future studies. We anticipate that this review will serve as a guiding resource for researchers to deepen the application of GNNs in single-cell omics.