scGALA: Graph Link Prediction Based Cell Alignment for Comprehensive Data Integration

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Abstract

Single-cell technologies have transformed our understanding of cellular heterogeneity through multimodal data acquisition. However, robust cell alignment remains a major challenge for data integration and harmonization, including batch correction, label transfer, and multiomics integration. Many existing methods constrain alignment based on rigid feature-wise distance metrics, limiting their ability to capture accurate cell correspondence across diverse cell populations and conditions. We introduce scGALA, a graph-based learning framework that redefines cell alignment by combining graph attention networks with a score-driven, task-independent optimization strategy. scGALA constructs enriched graphs of cell–cell relationships by integrating gene expression profiles with auxiliary information such as spatial coordinates and iteratively refines alignment via self-supervised graph link prediction, where a deep neural network is trained to identify and reinforce high-confidence correspondences across datasets. In extensive benchmarks, scGALA identifies over 25 percent more high-confidence alignments without compromising accuracy. By improving the core step of cell alignment, scGALA serves as a versatile enhancer for a wide range of single-cell data integration tasks.

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