用排序代替回归,提升抗体-抗原亲和力预测精度
AbLWR:A Context-Aware Listwise Ranking Framework for Antibody-Antigen Binding Affinity Prediction via Positive-Unlabeled Learning
- 将亲和力预测转为列表级排序,缓解标签稀缺问题
- 在随机交叉验证中P@1提升超10%,显著优于现有方法
- 适合抗体药物设计者,尤其擅长区分细微突变差异
准确预测抗体-抗原结合亲和力对治疗设计至关重要,但受限于标签极度稀疏及抗原变异的复杂性。本文提出AbLWR框架,将传统的亲和力回归任务重构为列表级排序问题。为缓解标签稀疏,引入正-未标记(PU)学习机制,结合双层对比目标与元优化标签精炼以学习鲁棒表征。针对抗原变异,采用同源抗原采样策略,并利用多头自注意力(MHSA)显式建模训练列表内样本间关系,捕捉细微亲和力差异。大量实验表明,AbLWR显著优于当前最优基线,在随机交叉验证中Precision@1(P@1)提升超过10%。流感病毒与IL-33的案例研究验证其实际应用价值,展现出在区分微小病毒突变时的稳定排序能力,并能高效筛选出高潜力候选分子用于湿实验验证。
原文摘要 · Abstract (English)
Accurate prediction of antibody-antigen binding affinity is fundamental to therapeutic design, yet remains constrained by severe label sparsity and the complexity of antigenic variations. In this paper, we propose AbLWR (Antibody-antigen binding affinity List-Wise Ranking), a novel framework that reformulates the conventional affinity regression task as a listwise ranking problem. To mitigate label sparsity, AbLWR incorporates a PU (Positive-Unlabeled) learning mechanism leveraging a dual-level contrastive objective and meta-optimized label refinement to learn robust representations. Furthermore, we address antigenic variation by employing a homologous antigen sampling strategy where Multi-Head Self-Attention (MHSA) explicitly models inter-sample relationships within training lists to capture subtle affinity nuances. Extensive experiments demonstrate that AbLWR significantly outperforms state-of-the-art baselines, improving the Precision@1 (P@1) by over 10$\%$ in randomized cross-validation experiments. Notably, case studies on Influenza and IL-33 validate its practical utility, demonstrating robust ranking consistency in distinguishing subtle viral mutations and efficiently prioritizing top-tier candidates for wet-lab screening.
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