JBHI Journal 2026 Journal Article
DPGOK: A Deep Learning-Based Method for Protein Function Prediction by Fusing GO Knowledge With Protein Features
- Qiurong Yang
- Wenkang Wang
- Wei Fan
- Ruiqing Zheng
- Min Li
Accurately predicting protein functions is critical for understanding disease mechanisms and discovering potential drug targets. Gene Ontology (GO), with its hierarchical and semantic information, provides valuable context that can be integrated to improve prediction accuracy. Recently, several existing methods have attempted to integrate GO knowledge with protein sequence features for function prediction. However, these methods ignore the fact that GO embeddings should be tailored to proteins to reflect protein-specific functional relevance. To address this limitation, we proposed DPGOK, a deep learning-based method that fused protein-aware GO representations with protein features for function prediction. DPGOK first learns GO semantic representations with a knowledge graph loss and further generates protein-aware GO embeddings under the guidance of protein features. Results show that DPGOK outperforms state-of-the-art methods across all GO domains. Additional experiments demonstrated that DPGOK is capable of discovering hierarchically deeper and more informative functions for target proteins. Ablation studies revealed that the knowledge graph loss we introduced contributes to more stable and semantically coherent GO representations across different domains. Finally, we find that the predictive performance can be further improved when DPGOK is combined with homology-based approaches.