融合语义与结构信息,提升蛋白质功能预测的泛化能力
STAR-GO: Improving Protein Function Prediction by Learning to Hierarchically Integrate Ontology-Informed Semantic Embeddings
- 用Transformer联合建模基因本体术语的文本定义与层级结构
- 在未见术语上实现优异零样本预测性能,准确率显著提升
- 适合生物信息学、药物发现领域研究者快速定位蛋白功能
准确预测蛋白质功能对解析分子机制和推动生物医学发现至关重要。然而,实验注释远远落后于蛋白质序列数据的快速增长。计算方法通过将蛋白质关联到基因本体(GO)术语来弥补这一差距,这些术语通过层级关系和文本定义编码功能知识。但现有模型常偏重单一模态,限制了泛化能力,尤其在面对不断演进的本体中新增或未见的GO术语时,导致已有模型迅速过时。我们提出STAR-GO,一种基于Transformer的框架,联合建模GO术语的语义与结构特征,以增强零样本蛋白质功能预测。STAR-GO将文本定义与本体图结构整合,学习统一的GO表示,并按层级顺序传播信息,从通用到具体。这些表示随后与蛋白质序列嵌入对齐,捕捉序列-功能关联。STAR-GO在多个基准上达到最优性能,展现出在零样本场景下的卓越泛化能力,验证了语义与结构融合对鲁棒、可适应功能预测的有效性。代码已公开于https://github.com/boun-tabi-lifelu/stargo。
原文摘要 · Abstract (English)
Accurate prediction of protein function is essential for elucidating molecular mechanisms and advancing biological and therapeutic discovery. Yet experimental annotation lags far behind the rapid growth of protein sequence data. Computational approaches address this gap by associating proteins with Gene Ontology (GO) terms, which encode functional knowledge through hierarchical relations and textual definitions. However, existing models often emphasize one modality over the other, limiting their ability to generalize, particularly to unseen or newly introduced GO terms that frequently arise as the ontology evolves, and making the previously trained models outdated. We present STAR-GO, a Transformer-based framework that jointly models the semantic and structural characteristics of GO terms to enhance zero-shot protein function prediction. STAR-GO integrates textual definitions with ontology graph structure to learn unified GO representations, which are processed in hierarchical order to propagate information from general to specific terms. These representations are then aligned with protein sequence embeddings to capture sequence-function relationships. STAR-GO achieves state-of-the-art performance and superior zero-shot generalization, demonstrating the utility of integrating semantics and structure for robust and adaptable protein function prediction. Code is available at https://github.com/boun-tabi-lifelu/stargo.
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