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DeepPhosPPI:一种用于预测磷酸化对蛋白质-蛋白质相互作用影响的深度学习框架,该框架采用了注意力卷积神经网络和变换器。

DeepPhosPPI: a deep learning framework with attention-CNN and transformer for predicting phosphorylation effects on protein-protein interactions.

作者信息

Gong Yinyin, Li Rui, Liu Yan, Wang Jilong, Chen Danny Z, Kwoh Chee Keong

机构信息

College of Computer Science and Electronic Engineering, Hunan University, Changsha, 410083, China.

College of Computing and Data Science, Nanyang Technological University, 639798, Singapore.

出版信息

Brief Bioinform. 2025 Sep 6;26(5). doi: 10.1093/bib/bbaf462.

Abstract

Protein phosphorylation regulates protein function and cellular signaling pathways, and is strongly associated with diseases, including neurodegenerative disorders and cancer. Phosphorylation plays a critical role in regulating protein activity and cellular signaling by modulating protein-protein interactions (PPIs). It alters binding affinities and interaction networks, thereby influencing biological processes and maintaining cellular homeostasis. Experimental validation of these effects is labor-intensive and expensive, highlighting the need for efficient computational approaches. We propose DeepPhosPPI, the first sequence-based deep learning framework for phosphorylation effects on PPIs prediction, which employs the pre-trained protein language model for feature embedding, with ProtBERT and ESM-2 as alternative backbone encoders. By combining attention-based convolutional neural network and Transformer models, DeepPhosPPI accurately predicts phosphorylation effects. The experimental results show that DeepPhosPPI consistently outperforms state-of-the-art methods in multiple tasks, including functional sites identification and regulatory effect classification.

摘要

蛋白质磷酸化调节蛋白质功能和细胞信号通路,并且与包括神经退行性疾病和癌症在内的多种疾病密切相关。磷酸化通过调节蛋白质-蛋白质相互作用(PPI)在调控蛋白质活性和细胞信号传导中发挥关键作用。它改变结合亲和力和相互作用网络,从而影响生物过程并维持细胞内稳态。对这些效应进行实验验证既费力又昂贵,这凸显了高效计算方法的必要性。我们提出了DeepPhosPPI,这是首个基于序列的用于预测磷酸化对PPI影响的深度学习框架,它采用预训练的蛋白质语言模型进行特征嵌入,以ProtBERT和ESM-2作为替代的主干编码器。通过结合基于注意力的卷积神经网络和Transformer模型,DeepPhosPPI能够准确预测磷酸化效应。实验结果表明,DeepPhosPPI在包括功能位点识别和调控效应分类在内的多个任务中始终优于现有方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b86d/12414479/503da8e3d27d/bbaf462f1.jpg

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