Accurately identifying cell types in single-cell RNA sequencing data is critical for understanding cellular differentiation and pathological mechanisms in downstream analysis. As traditional biological approaches are laborious and time-intensive, it is imperative to develop computational biology methods for cell classification. However, it remains a challenge for existing methods to adequately utilize the potential gene expression information within the vast amount of unlabeled cell data, which limits their classification and generalization performance. Therefore, we propose a novel self-supervised graph representation learning framework for single-cell classification, named scSSGC. Specifically, in the pre-training stage of self-supervised learning, multiple K-means clustering tasks conducted on unlabeled cell data are jointly employed for model training, thereby mitigating the issue of limited labeled data. To effectively capture the potential interactions among cells, we introduce a locally augmented graph neural network to enhance the information aggregation capability for nodes with fewer neighbors in the cell graph. A range of benchmark experiments demonstrates that scSSGC outperforms existing state-of-the-art cell classification methods. More importantly, scSSGC provides stable performance when faced with cross-datasets, indicating better generalization ability.

Keywords: Cell–cell network; Graph neural network; Self-supervised learning; Single-cell classification.

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