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用于多组学癌症预后预测与分析的局部增强图神经网络

Local augmented graph neural network for multi-omics cancer prognosis prediction and analysis.

作者信息

Zhang Yongqing, Xiong Shuwen, Wang Zixuan, Liu Yuhang, Luo Hong, Li Beichen, Zou Quan

机构信息

School of Computer Science, Chengdu University of Information Technology, Chengdu, 610225, China.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 610054, China.

出版信息

Methods. 2023 May;213:1-9. doi: 10.1016/j.ymeth.2023.02.011. Epub 2023 Mar 16.

Abstract

Cancer prognosis prediction and analysis can help patients understand expected life and help clinicians provide correct therapeutic guidance. Thanks to the development of sequencing technology, multi-omics data, and biological networks have been used for cancer prognosis prediction. Besides, graph neural networks can simultaneously consider multi-omics features and molecular interactions in biological networks, becoming mainstream in cancer prognosis prediction and analysis. However, the limited number of neighboring genes in biological networks restricts the accuracy of graph neural networks. To solve this problem, a local augmented graph convolutional network named LAGProg is proposed in this paper for cancer prognosis prediction and analysis. The process follows: first, given a patient's multi-omics data features and biological network, the corresponding augmented conditional variational autoencoder generates features. Then, the generated augmented features and the original features are fed into a cancer prognosis prediction model to complete the cancer prognosis prediction task. The conditional variational autoencoder consists of two parts: encoder-decoder. In the encoding phase, an encoder learns the conditional distribution of the multi-omics data. As a generative model, a decoder takes the conditional distribution and the original feature as inputs to generate the enhanced features. The cancer prognosis prediction model consists of a two-layer graph convolutional neural network and a Cox proportional risk network. The Cox proportional risk network consists of fully connected layers. Extensive experiments on 15 real-world datasets from TCGA demonstrated the effectiveness and efficiency of the proposed method in predicting cancer prognosis. LAGProg improved the C-index values by an average of 8.5% over the state-of-the-art graph neural network method. Moreover, we confirmed that the local augmentation technique could enhance the model's ability to represent multi-omics features, improve the model's robustness to missing multi-omics features, and prevent the model's over-smoothing during training. Finally, based on genes identified through differential expression analysis, we discovered 13 prognostic markers highly associated with breast cancer, among which ten genes have been proved by literature review.

摘要

癌症预后预测与分析有助于患者了解预期寿命,并帮助临床医生提供正确的治疗指导。得益于测序技术的发展,多组学数据和生物网络已被用于癌症预后预测。此外,图神经网络能够同时考虑生物网络中的多组学特征和分子相互作用,成为癌症预后预测与分析的主流方法。然而,生物网络中相邻基因数量有限,限制了图神经网络的准确性。为解决这一问题,本文提出了一种名为LAGProg的局部增强图卷积网络用于癌症预后预测与分析。具体过程如下:首先,给定患者的多组学数据特征和生物网络,相应的增强条件变分自编码器生成特征。然后,将生成的增强特征和原始特征输入到癌症预后预测模型中,完成癌症预后预测任务。条件变分自编码器由编码器-解码器两部分组成。在编码阶段,编码器学习多组学数据的条件分布。作为生成模型,解码器将条件分布和原始特征作为输入来生成增强特征。癌症预后预测模型由一个两层图卷积神经网络和一个Cox比例风险网络组成。Cox比例风险网络由全连接层组成。在来自TCGA的15个真实世界数据集上进行的大量实验证明了所提方法在预测癌症预后方面的有效性和效率。与最先进的图神经网络方法相比,LAGProg的C指数值平均提高了8.5%。此外,我们证实局部增强技术可以增强模型表示多组学特征的能力,提高模型对缺失多组学特征的鲁棒性,并防止模型在训练过程中过度平滑。最后,基于通过差异表达分析确定的基因,我们发现了13个与乳腺癌高度相关的预后标志物,其中有10个基因已被文献综述证实。

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