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利用多视图图自动编码器预测人类癌症中的合成致死相互作用。

Prediction of Synthetic Lethal Interactions in Human Cancers Using Multi-View Graph Auto-Encoder.

出版信息

IEEE J Biomed Health Inform. 2021 Oct;25(10):4041-4051. doi: 10.1109/JBHI.2021.3079302. Epub 2021 Oct 5.

Abstract

Synthetic lethality (SL) is a very important concept for the development of targeted anticancer drugs. However, experimental methods for SL detection often suffer from various issues like high cost and low consistency across cell lines. Hence, computational methods for predicting novel SLs have recently emerged as complements for wet-lab experiments. In addition, SL data can be represented as a graph where nodes are genes and edges are the SL interactions. It is thus motivated to design advanced graph-based machine learning algorithms for SL prediction. In this paper, we propose a novel SL prediction method using Multi-view Graph Auto-Encoder (SLMGAE). We consider the SL graph as the main view and the graphs from other data sources (e.g., PPI, GO, etc.) as support views. Multiple Graph Auto-Encoders (GAEs) are implemented to reconstruct the graphs for different views. We further design an attention mechanism, which assigns different weights for support views, to combine all the reconstructed graphs for SL prediction. The overall SLMGAE model is then trained by minimizing both the reconstruction error and prediction error. Experimental results on the SynLethDB dataset show that SLMGAE outperforms state-of-the-arts. The case studies on novel predicted SLs also illustrate the effectiveness of our SLMGAE method.

摘要

合成致死性(SL)是开发靶向抗癌药物的一个非常重要的概念。然而,SL 检测的实验方法常常存在成本高、细胞系间一致性低等问题。因此,最近出现了预测新的 SL 的计算方法,作为湿实验的补充。此外,SL 数据可以表示为一个图,其中节点是基因,边是 SL 相互作用。因此,设计先进的基于图的机器学习算法来进行 SL 预测是很有意义的。在本文中,我们提出了一种新的基于多视图图自动编码器(SLMGAE)的 SL 预测方法。我们将 SL 图视为主要视图,并将来自其他数据源(如 PPI、GO 等)的图作为支持视图。实现了多个图自动编码器(GAEs)来重建不同视图的图。我们进一步设计了一种注意力机制,为支持视图分配不同的权重,以组合所有用于 SL 预测的重建图。最后,通过最小化重建误差和预测误差来训练整个 SLMGAE 模型。在 SynLethDB 数据集上的实验结果表明,SLMGAE 优于现有的最先进方法。对新预测的 SL 的案例研究也说明了我们的 SLMGAE 方法的有效性。

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