通过联合重构与对比学习,提升未知蛋白间的相互作用预测能力
Joint Masked Reconstruction and Contrastive Learning for Mining Interactions Between Proteins
- 分两阶段建模:先用图注意力重建残基结构,再用多图对比学习挖掘互作信号
- 在三个数据集上均超越现有最优模型,尤其对未见蛋白表现更优
- 适合需要预测新蛋白互作的生物医学研究者使用
蛋白质-蛋白质互作(PPI)预测对于揭示细胞运作机制具有重要意义,对药物研发和临床治疗有重要应用价值。目前多数方法集中于氨基酸序列分析,基于蛋白质结构的研究仍处于初级阶段。尽管近年出现若干结构基算法,但仍面临两大挑战:(1)提取蛋白质内在结构信息需大量计算资源;(2)模型过度依赖已见蛋白数据,难以发现未知蛋白间的互作线索。为此,本文提出一种融合掩码重建与对比学习的新方法JmcPPI。该方法将PPI预测分为两个阶段:在残基结构编码阶段,设计两项特征重建任务,并利用图注意力机制捕捉残基间结构信息;在蛋白互作推理阶段,对原始PPI图进行扰动,采用多图对比学习策略,深入挖掘新蛋白的外在互作信息。在三个常用PPI数据集上的实验表明,JmcPPI在不同数据划分方案下均优于现有最优基线模型。代码已公开于https://github.com/lijfrank-open/JmcPPI。
原文摘要 · Abstract (English)
Protein-protein interaction (PPI) prediction is an instrumental means in elucidating the mechanisms underlying cellular operations, holding significant practical implications for the realms of pharmaceutical development and clinical treatment. Presently, the majority of research methods primarily concentrate on the analysis of amino acid sequences, while investigations predicated on protein structures remain in the nascent stages of exploration. Despite the emergence of several structure-based algorithms in recent years, these are still confronted with inherent challenges: (1) the extraction of intrinsic structural information of proteins typically necessitates the expenditure of substantial computational resources; (2) these models are overly reliant on seen protein data, struggling to effectively unearth interaction cues between unknown proteins. To further propel advancements in this domain, this paper introduces a novel PPI prediction method jointing masked reconstruction and contrastive learning, termed JmcPPI. This methodology dissects the PPI prediction task into two distinct phases: during the residue structure encoding phase, JmcPPI devises two feature reconstruction tasks and employs graph attention mechanism to capture structural information between residues; during the protein interaction inference phase, JmcPPI perturbs the original PPI graph and employs a multi-graph contrastive learning strategy to thoroughly mine extrinsic interaction information of novel proteins. Extensive experiments conducted on three widely utilized PPI datasets demonstrate that JmcPPI surpasses existing optimal baseline models across various data partition schemes. The associated code can be accessed via https://github.com/lijfrank-open/JmcPPI.
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