arXiv:2409.00610q-bio.QMcs.LG2024-09被引 1

用图像检测思路预测蛋白功能位点,提升定位精度

ProteinRPN: Towards Accurate Protein Function Prediction with Graph-Based Region Proposals

  • 借鉴目标检测的区域提议机制,识别潜在功能区域
  • 在多个GO分类任务中准确率提升,能精确定位关键残基
  • 适合结构生物学与药物设计领域研究者参考

蛋白质功能预测是生物信息学中的关键任务,对理解生物过程和疾病机制具有重要意义。尽管序列与功能的关系已被广泛研究,但将蛋白质结构映射到功能仍面临巨大挑战。现有模型(如CNN和图神经网络)多从回顾性视角出发,难以揭示关键残基的功能意义,导致性能不佳。受计算机视觉中区域提议网络启发,本文提出蛋白质区域提议网络(ProteinRPN),其区域提议模块识别潜在功能区域(锚点),并通过层次感知节点丢弃池化层,优先保留具有明确二级结构和空间邻近性的节点。通过注意力机制增强预测功能节点的表征,并输入图多重集变换器(Graph Multiset Transformer),该模型在扰动蛋白结构上使用监督对比学习(SupCon)和InfoNCE损失进行训练。实验表明,该方法在预测基因本体(GO)术语方面表现显著提升,有效定位功能残基。所提出的框架为蛋白质功能注释提供了一种鲁棒且可扩展的解决方案,推动了计算生物学中蛋白质结构-功能关系的理解。

原文摘要 · Abstract (English)

Protein function prediction is a crucial task in bioinformatics, with significant implications for understanding biological processes and disease mechanisms. While the relationship between sequence and function has been extensively explored, translating protein structure to function continues to present substantial challenges. Various models, particularly, CNN and graph-based deep learning approaches that integrate structural and functional data, have been proposed to address these challenges. However, these methods often fall short in elucidating the functional significance of key residues essential for protein functionality, as they predominantly adopt a retrospective perspective, leading to suboptimal performance. Inspired by region proposal networks in computer vision, we introduce the Protein Region Proposal Network (ProteinRPN) for accurate protein function prediction. Specifically, the region proposal module component of ProteinRPN identifies potential functional regions (anchors) which are refined through the hierarchy-aware node drop pooling layer favoring nodes with defined secondary structures and spatial proximity. The representations of the predicted functional nodes are enriched using attention mechanisms and subsequently fed into a Graph Multiset Transformer, which is trained with supervised contrastive (SupCon) and InfoNCE losses on perturbed protein structures. Our model demonstrates significant improvements in predicting Gene Ontology (GO) terms, effectively localizing functional residues within protein structures. The proposed framework provides a robust, scalable solution for protein function annotation, advancing the understanding of protein structure-function relationships in computational biology.

蛋白功能预测图神经网络结构生物学

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