arXiv:2507.02724cs.LGq-bio.BM2025-07被引 2

通过分层对比学习,实现跨物种蛋白质互作精准预测。

Hierarchical Multi-Label Contrastive Learning for Protein-Protein Interaction Prediction Across Organisms

  • 构建分层对比框架,对齐蛋白序列与功能层级特征。
  • 在多个数据集上超越现有方法,低数据场景下仍表现稳健。
  • 无需重训练即可零样本迁移至新物种,适合稀疏数据场景。

近年来,人工智能在科学领域的进展凸显了对比学习在连接异构生物数据模态方面的潜力。基于此范式,我们提出HIPPO(HIerarchical Protein-Protein interaction prediction across Organisms),一种用于跨物种蛋白质互作(PPI)预测的分层对比框架。该框架通过多层级生物表征匹配,对齐蛋白序列及其层级属性。提出的分层对比损失函数模拟了蛋白质功能类别的结构化关系。框架通过数据驱动的惩罚机制自适应融合领域和家族知识,强制学习到的嵌入空间与蛋白功能内在层级保持一致。在基准数据集上的实验表明,HIPPO达到当前最优性能,在低数据条件下表现出鲁棒性。值得注意的是,该模型在不重新训练的情况下展现出强大的零样本迁移能力,可在实验数据有限的未充分表征或罕见生物中实现可靠的PPI预测与功能推断。进一步分析揭示,分层特征融合对捕捉保守的相互作用决定因素(如结合基序和功能注释)至关重要。本工作推进了跨物种PPI预测,并为稀疏或不平衡多物种数据场景下的交互预测提供了统一框架。

原文摘要 · Abstract (English)

Recent advances in AI for science have highlighted the power of contrastive learning in bridging heterogeneous biological data modalities. Building on this paradigm, we propose HIPPO (HIerarchical Protein-Protein interaction prediction across Organisms), a hierarchical contrastive framework for protein-protein interaction(PPI) prediction, where protein sequences and their hierarchical attributes are aligned through multi-tiered biological representation matching. The proposed approach incorporates hierarchical contrastive loss functions that emulate the structured relationship among functional classes of proteins. The framework adaptively incorporates domain and family knowledge through a data-driven penalty mechanism, enforcing consistency between the learned embedding space and the intrinsic hierarchy of protein functions. Experiments on benchmark datasets demonstrate that HIPPO achieves state-of-the-art performance, outperforming existing methods and showing robustness in low-data regimes. Notably, the model demonstrates strong zero-shot transferability to other species without retraining, enabling reliable PPI prediction and functional inference even in less characterized or rare organisms where experimental data are limited. Further analysis reveals that hierarchical feature fusion is critical for capturing conserved interaction determinants, such as binding motifs and functional annotations. This work advances cross-species PPI prediction and provides a unified framework for interaction prediction in scenarios with sparse or imbalanced multi-species data.

蛋白质互作对比学习跨物种零样本

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