融合多模态信息,提升抗体结合位点预测精度
CAME-AB: Cross-Modality Attention with Mixture-of-Experts for Antibody Binding Site Prediction
- 引入五种生物特征模态,动态加权融合增强跨模态推理
- 在多个数据集上实现更高精确率、召回率与F1分数
- 适合抗体药物设计与计算免疫学研究者使用
抗体结合位点预测在计算免疫学和治疗性抗体设计中至关重要。现有基于序列或结构的方法依赖单一视图特征,难以识别抗原上的抗体特异性结合位点。本文提出CAME-AB,一种基于混合专家(MoE)的跨模态注意力框架,整合原始氨基酸编码、BLOSUM替代谱、预训练语言模型嵌入、结构感知特征及GCN优化的生化图等五类生物相关模态,构建统一多模态表征。通过自适应模态融合模块,动态学习各模态的全局相关性与输入特定贡献权重。结合Transformer编码器与MoE模块,促进特征专业化与容量扩展。引入监督对比学习目标,显式塑造潜在空间几何结构,增强类内紧凑性与类间可分性。训练中采用随机权重平均以提升优化稳定性与泛化能力。在基准抗体-抗原数据集上的大量实验表明,CAME-AB在精确率、召回率、F1分数、AUC-ROC与MCC等多个指标上持续优于强基线模型。消融实验证实了各组件有效性及多模态融合的优势。模型实现细节与代码已公开于https://anonymous.4open.science/r/CAME-AB-C525。
原文摘要 · Abstract (English)
Antibody binding site prediction plays a pivotal role in computational immunology and therapeutic antibody design. Existing sequence or structure methods rely on single-view features and fail to identify antibody-specific binding sites on the antigens. In this paper, we propose \textbf{CAME-AB}, a novel Cross-modality Attention framework with a Mixture-of-Experts (MoE) backbone for robust antibody binding site prediction. CAME-AB integrates five biologically grounded modalities, including raw amino acid encodings, BLOSUM substitution profiles, pretrained language model embeddings, structure-aware features, and GCN-refined biochemical graphs, into a unified multimodal representation. To enhance adaptive cross-modal reasoning, we propose an \emph{adaptive modality fusion} module that learns to dynamically weight each modality based on its global relevance and input-specific contribution. A Transformer encoder combined with an MoE module further promotes feature specialization and capacity expansion. We additionally incorporate a supervised contrastive learning objective to explicitly shape the latent space geometry, encouraging intra-class compactness and inter-class separability. To improve optimization stability and generalization, we apply stochastic weight averaging during training. Extensive experiments on benchmark antibody-antigen datasets demonstrate that CAME-AB consistently outperforms strong baselines on multiple metrics, including Precision, Recall, F1-score, AUC-ROC, and MCC. Ablation studies further validate the effectiveness of each architectural component and the benefit of multimodal feature integration. The model implementation details and the codes are available on https://anonymous.4open.science/r/CAME-AB-C525
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