通过重排子序列预训练,提升小样本下的化合物-蛋白相互作用预测能力。
Zero-Shot Learning with Subsequence Reordering Pretraining for Compound-Protein Interaction
- 用子序列重排方式学习蛋白依赖关系,捕捉局部结构特征。
- 在少量数据下仍保持高性能,零样本场景提升显著。
- 适合数据稀缺的药物研发场景,对小样本任务友好。
由于化学空间广阔且不断出现未表征蛋白,零样本化合物-蛋白相互作用(CPI)预测更贴近真实药物研发挑战。现有方法虽在特定任务中表现良好,但仍存在两大问题:(1) 仅基于局部或完整蛋白序列的表示学习常忽略子序列间的复杂依赖关系,而这些关系对空间结构和结合特性预测至关重要;(2) 依赖大规模或稀疏多模态蛋白数据集,需大量训练数据与计算资源,限制可扩展性与效率。为此,我们提出一种新方法,通过子序列重排进行蛋白表示预训练,显式建模子序列间依赖关系。同时引入长度可变的蛋白增强策略,确保在小数据集上的优异预训练性能。通过与多种基线模型结合评估,结果表明该方法显著提升基线模型在CPI任务中的表现,尤其在挑战性的零样本场景中。相较于现有预训练模型,本模型在数据稀缺情况下表现出更优性能。代码已开源:https://github.com/Hoch-Zhang/PSRP-CPI。
原文摘要 · Abstract (English)
Given the vastness of chemical space and the ongoing emergence of previously uncharacterized proteins, zero-shot compound-protein interaction (CPI) prediction better reflects the practical challenges and requirements of real-world drug development. Although existing methods perform adequately during certain CPI tasks, they still face the following challenges: (1) Representation learning from local or complete protein sequences often overlooks the complex interdependencies between subsequences, which are essential for predicting spatial structures and binding properties. (2) Dependence on large-scale or scarce multimodal protein datasets demands significant training data and computational resources, limiting scalability and efficiency. To address these challenges, we propose a novel approach that pretrains protein representations for CPI prediction tasks using subsequence reordering, explicitly capturing the dependencies between protein subsequences. Furthermore, we apply length-variable protein augmentation to ensure excellent pretraining performance on small training datasets. To evaluate the model's effectiveness and zero-shot learning ability, we combine it with various baseline methods. The results demonstrate that our approach can improve the baseline model's performance on the CPI task, especially in the challenging zero-shot scenario. Compared to existing pre-training models, our model demonstrates superior performance, particularly in data-scarce scenarios where training samples are limited. Our implementation is available at https://github.com/Hoch-Zhang/PSRP-CPI.
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