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基于多头注意力机制的图嵌入表示学习预测噬菌体-宿主相互作用的有效模型。

An Effective Model for Predicting Phage-Host Interactions Via Graph Embedding Representation Learning With Multi-Head Attention Mechanism.

出版信息

IEEE J Biomed Health Inform. 2023 Jun;27(6):3061-3071. doi: 10.1109/JBHI.2023.3261319. Epub 2023 Jun 5.

Abstract

In the treatment of bacterial infectious diseases, overuse of antibiotics may lead to not only bacterial resistance to antibiotics but also dysbiosis of beneficial bacteria which are essential for maintaining normal human life activities. Instead, phage therapy, which invades and lyses specific pathogenic bacteria without affecting beneficial bacteria, becomes more and more popular to treat bacterial infectious diseases. For the effective phage therapy, it requires to accurately predict potential phage-host interactions from heterogeneous information network consisting of bacteria and phages. Although many models have been proposed for predicting phage-host interactions, most methods fail to consider fully the sparsity and unconnectedness of phage-host heterogeneous information network, deriving the undesirable performance on phage-host interactions prediction. To address the challenge, we propose an effective model called GERMAN-PHI for predicting Phage-Host Interactions via Graph Embedding Representation learning with Multi-head Attention mechaNism. In GERMAN-PHI, the multi-head attention mechanism is utilized to learn representations of phages and hosts from multiple perspectives of phage-host associations, addressing the sparsity and unconnectedness in phage-host heterogeneous information network. More specifically, a module of GAT with talking-heads is employed to learn representations of phages and bacteria, on which neural induction matrix completion is conducted to reconstruct the phage-host association matrix. Results of comprehensive experiments demonstrate that GERMAN-PHI performs better than the state-of-the-art methods on phage-host interactions prediction. In addition, results of case study for two high-risk human pathogens show that GERMAN-PHI can predict validated phages with high accuracy, and some potential or new associated phages are provided as well.

摘要

在治疗细菌性传染病时,抗生素的过度使用不仅会导致细菌对抗生素产生耐药性,还会导致对维持正常人体生命活动至关重要的有益细菌的失调。相反,噬菌体治疗(通过入侵和裂解特定的致病菌而不影响有益细菌)越来越受欢迎,用于治疗细菌性传染病。为了有效地进行噬菌体治疗,需要从由细菌和噬菌体组成的异质信息网络中准确预测潜在的噬菌体-宿主相互作用。尽管已经提出了许多用于预测噬菌体-宿主相互作用的模型,但大多数方法都没有充分考虑噬菌体-宿主异质信息网络的稀疏性和不连通性,导致在噬菌体-宿主相互作用预测方面表现不佳。为了解决这一挑战,我们提出了一种名为 GERMAN-PHI 的有效模型,该模型通过使用多头注意力机制的图嵌入表示学习来预测噬菌体-宿主相互作用。在 GERMAN-PHI 中,多头注意力机制用于从噬菌体-宿主关联的多个角度学习噬菌体和宿主的表示,解决了噬菌体-宿主异质信息网络中的稀疏性和不连通性问题。更具体地说,我们使用具有多头的 GAT 模块来学习噬菌体和细菌的表示,然后对其进行神经诱导矩阵补全,以重建噬菌体-宿主关联矩阵。综合实验结果表明,GERMAN-PHI 在噬菌体-宿主相互作用预测方面的性能优于最先进的方法。此外,对两种高风险人类病原体的案例研究结果表明,GERMAN-PHI 可以高精度地预测已验证的噬菌体,并且还提供了一些潜在的或新的相关噬菌体。

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