用上下文学习提升抗体亲和力排序精度,尤其在数据少时更有效。
AbICL: In-Context Learning for Antigen-Specific Antibody Affinity Ranking

- 基于结构编码器与上下文排名头,通过元训练实现无需梯度更新的上下文适应。
- 在AbRank基准上多数数据划分和评估指标上优于现有基线方法。
- 小样本下依赖上下文匹配度,分布偏移或精细区分时优势更明显,适合抗体发现场景。
根据结合亲和力准确排序抗体候选物对治疗性抗体发现至关重要。现有方法独立处理亲和力比较,忽略其他标注比较中的上下文信息,难以捕捉抗原特异性结合格局。对于许多靶点抗原,仅有少量实验表征的亲和力比较数据可用。关键问题是:模型能否利用这些已有比较,推断出有助于后续亲和力排序的抗原特异性模式?这种从标注示例中学习的形式类似于上下文学习(In-Context Learning, ICL),启发我们从ICL视角重新思考抗体亲和力排序。为此,我们提出AbICL,一种面向抗原特异性抗体亲和力排序的ICL框架。AbICL结合预训练结构编码器与上下文排名头,并采用分段元训练策略,使模型在测试时无需梯度更新即可利用支持示例进行自适应。在AbRank基准上的实验表明,AbICL在几乎所有数据划分和评估基准上均持续优于现有排序基线。进一步分析显示,上下文示例的价值取决于其与目标推理任务的匹配程度,在分布偏移和细粒度亲和力区分下愈发显著。这些发现凸显了ICL作为抗原特异性亲和力排序有效范式,尤其在单一全局排序函数不足的挑战性场景中。
原文摘要 · Abstract (English)
Accurate ranking of antibody candidates according to their binding affinity is essential for therapeutic antibody discovery. However, existing methods treat affinity comparisons independently and ignore the contextual information encoded in other labeled comparisons, limiting their ability to capture antigen-specific binding landscapes. For many target antigens, a small number of experimentally characterized affinity comparisons are often available. An important question is whether the model can exploit these existing comparisons to infer antigen-specific ranking patterns that facilitate subsequent affinity ranking. This form of learning from labeled demonstrations closely resembles the paradigm of In-Context Learning, motivating us to revisit antibody affinity ranking from an ICL perspective. To this end, we propose AbICL, an ICL framework for antigen-specific antibody affinity ranking. AbICL combines a pretrained structural encoder with a context ranking head and is trained with an episodic meta-training strategy that enables the model to leverage support demonstrations for test-time adaptation without gradient updates. Experiments on the AbRank benchmark demonstrate that AbICL consistently outperforms existing ranking baselines across almost all data splits and evaluation benchmarks. Further analysis shows that the value of contextual demonstrations depends on how well they match the target inference task, and becomes increasingly pronounced under distribution shift and fine-grained affinity discrimination. These findings highlight the potential of ICL as an effective paradigm for antigen-specific antibody affinity ranking, particularly in challenging settings where a single global ranking function is insufficient.
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