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将药效团概念与图神经网络相结合用于化学性质预测与解释。

Integrating concept of pharmacophore with graph neural networks for chemical property prediction and interpretation.

作者信息

Kong Yue, Zhao Xiaoman, Liu Ruizi, Yang Zhenwu, Yin Hongyan, Zhao Bowen, Wang Jinling, Qin Bingjie, Yan Aixia

机构信息

State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P. O. Box 53, Beijing, 100029, People's Republic of China.

Hyper-Dimension Insight Pharmaceuticals Ltd. Room 511, Block A, No. 2C, DongSanHuan North Road, Beijing, People's Republic of China.

出版信息

J Cheminform. 2022 Aug 4;14(1):52. doi: 10.1186/s13321-022-00634-3.

Abstract

Recently, graph neural networks (GNNs) have revolutionized the field of chemical property prediction and achieved state-of-the-art results on benchmark data sets. Compared with the traditional descriptor- and fingerprint-based QSAR models, GNNs can learn task related representations, which completely gets rid of the rules defined by experts. However, due to the lack of useful prior knowledge, the prediction performance and interpretability of the GNNs may be affected. In this study, we introduced a new GNN model called RG-MPNN for chemical property prediction that integrated pharmacophore information hierarchically into message-passing neural network (MPNN) architecture, specifically, in the way of pharmacophore-based reduced-graph (RG) pooling. RG-MPNN absorbed not only the information of atoms and bonds from the atom-level message-passing phase, but also the information of pharmacophores from the RG-level message-passing phase. Our experimental results on eleven benchmark and ten kinase data sets showed that our model consistently matched or outperformed other existing GNN models. Furthermore, we demonstrated that applying pharmacophore-based RG pooling to MPNN architecture can generally help GNN models improve the predictive power. The cluster analysis of RG-MPNN representations and the importance analysis of pharmacophore nodes will help chemists gain insights for hit discovery and lead optimization.

摘要

最近,图神经网络(GNNs)彻底改变了化学性质预测领域,并在基准数据集上取得了最优结果。与传统的基于描述符和指纹的定量构效关系(QSAR)模型相比,GNNs可以学习与任务相关的表示,完全摆脱了专家定义的规则。然而,由于缺乏有用的先验知识,GNNs的预测性能和可解释性可能会受到影响。在本研究中,我们引入了一种名为RG-MPNN的新GNN模型用于化学性质预测,该模型将药效团信息分层集成到消息传递神经网络(MPNN)架构中,具体而言,是以基于药效团的简化图(RG)池化的方式。RG-MPNN不仅从原子级消息传递阶段吸收了原子和键的信息,还从RG级消息传递阶段吸收了药效团的信息。我们在11个基准数据集和10个激酶数据集上的实验结果表明,我们的模型始终与其他现有GNN模型相当或优于它们。此外,我们证明将基于药效团的RG池化应用于MPNN架构通常可以帮助GNN模型提高预测能力。RG-MPNN表示的聚类分析和药效团节点的重要性分析将有助于化学家深入了解命中发现和先导优化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd52/9351086/8cfdf3ad1909/13321_2022_634_Fig1_HTML.jpg

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