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迈向用于在异质网络中识别癌症驱动基因的简化图神经网络

Towards simplified graph neural networks for identifying cancer driver genes in heterophilic networks.

作者信息

Li Xingyi, Xu Jialuo, Li Junming, Gu Jia, Shang Xuequn

机构信息

School of Computer Science, Northwestern Polytechnical University, Xi'an, 710072 Shaanxi, China.

Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518063 Guangdong, China.

出版信息

Brief Bioinform. 2024 Nov 22;26(1). doi: 10.1093/bib/bbae691.

Abstract

The identification of cancer driver genes is crucial for understanding the complex processes involved in cancer development, progression, and therapeutic strategies. Multi-omics data and biological networks provided by numerous databases enable the application of graph deep learning techniques that incorporate network structures into the deep learning framework. However, most existing methods do not account for the heterophily in the biological networks, which hinders the improvement of model performance. Meanwhile, feature confusion often arises in models based on graph neural networks in such graphs. To address this, we propose a Simplified Graph neural network for identifying Cancer Driver genes in heterophilic networks (SGCD), which comprises primarily two components: a graph convolutional neural network with representation separation and a bimodal feature extractor. The results demonstrate that SGCD not only performs exceptionally well but also exhibits robust discriminative capabilities compared to state-of-the-art methods across all benchmark datasets. Moreover, subsequent interpretability experiments on both the model and biological aspects provide compelling evidence supporting the reliability of SGCD. Additionally, the model can dissect gene modules, revealing clearer connections between driver genes in cancers. We are confident that SGCD holds potential in the field of precision oncology and may be applied to prognosticate biomarkers for a wide range of complex diseases.

摘要

识别癌症驱动基因对于理解癌症发生、发展及治疗策略中涉及的复杂过程至关重要。众多数据库提供的多组学数据和生物网络使得将网络结构纳入深度学习框架的图深度学习技术得以应用。然而,大多数现有方法并未考虑生物网络中的异质性,这阻碍了模型性能的提升。同时,在这类图中基于图神经网络的模型中常常会出现特征混淆。为解决这一问题,我们提出了一种用于在异质网络中识别癌症驱动基因的简化图神经网络(SGCD),它主要由两个部分组成:具有表示分离功能的图卷积神经网络和双峰特征提取器。结果表明,与所有基准数据集上的现有方法相比,SGCD不仅表现出色,而且具有强大的判别能力。此外,随后在模型和生物学方面的可解释性实验提供了有力证据,支持了SGCD的可靠性。此外,该模型可以剖析基因模块,揭示癌症中驱动基因之间更清晰的联系。我们相信,SGCD在精准肿瘤学领域具有潜力,可能会被应用于预测多种复杂疾病的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d6/11697181/844ef7b16f35/bbae691f1.jpg

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