Generative and Contrastive Self-Supervised Learning for Virulence Factor Identification Based on Protein-Protein...

Virulence factors (VFs), produced by pathogens, facilitate pathogenic microorganisms to invade, colonize, and damage the host cells. Accurate VF identification advances pathogenic mechanism understanding and provides novel anti-virulence targets. Existing models primarily utilize protein sequence features while overlooking the systematic protein-protein interaction (PPI) information, despite pathogenesis typically resulting from coordinated protein-protein actions. Moreover, a severe imbalance exists between virulence and non-virulence proteins, which causes existing models trained on balanced datasets by sampling to fail in incorporating proteins' inherent distributional characteristics, thus restricting generalization to real-world imbalanced data. To address these challenges, we propose a novel Generative and Contrastive self-supervised learning framework for Virulence Factor identification (GC-VF) that transforms VF identification into an imbalanced node classification task on graphs generated from PPI networks. The framework encompasses two core modules: the generative attribute reconstruction module learns attribute space representations via feature reconstruction, capturing intrinsic data patterns and reducing noise; the local contrastive learning module employs node-level contrastive learning to precisely capture local features and contextual information, avoiding global aggregation losses while ensuring node representations truly reflect inherent characteristics. Comprehensive benchmark experiments demonstrate that GC-VF outperforms baseline methods on naturally imbalanced datasets, exhibiting higher accuracy and stability, as well as providing a potential solution for accurate VF identification.