论文标题

用于预测生物网络上未观察到的节点特征的图形功能自动编码器

A Graph Feature Auto-Encoder for the Prediction of Unobserved Node Features on Biological Networks

论文作者

Hasibi, Ramin, Michoel, Tom

论文摘要

动机:分子相互作用网络总结了复杂的生物过程作为图,其结构在多个尺度上对生物学功能提供了信息。同时,OMICS技术测量了个体或实验条件之间基因,蛋白质或代谢物的变异或活性。整合生物网络和OMIC数据的互补观点是生物信息学的重要任务,但是现有方法将网络视为离散的结构,这些结构本质上很难与连续的节点特征或活动度量集成在一起。图形神经网络将图形节点映射到低维矢量空间表示形式中,并且可以训练以保持本地图结构和节点特征之间的相似性。 结果:我们使用图神经网络研究了大肠杆菌和小鼠中转录,蛋白质 - 蛋白质和遗传相互作用网络的表示。我们发现,这种表示形式解释了基因表达数据的很大一部分变化,并且将基因表达数据作为节点特征改善了嵌入中图的重建。我们进一步提出了一个新的端到端图形特征自动编码器,该功能是在功能重建任务上接受训练的,并表明它在预测未观察到的节点功能方面的性能要比在学习预测节点特征之前在学习之前接受了图形重建任务的自动编码器更好。当应用于单细胞RNASEQ数据中缺少数据的问题时,我们的图形功能自动编码器优于一种不使用蛋白质相互作用信息的最先进的归纳方法,显示了使用图表表示学习生物网络和OMICS数据的好处。

Motivation: Molecular interaction networks summarize complex biological processes as graphs, whose structure is informative of biological function at multiple scales. Simultaneously, omics technologies measure the variation or activity of genes, proteins, or metabolites across individuals or experimental conditions. Integrating the complementary viewpoints of biological networks and omics data is an important task in bioinformatics, but existing methods treat networks as discrete structures, which are intrinsically difficult to integrate with continuous node features or activity measures. Graph neural networks map graph nodes into a low-dimensional vector space representation, and can be trained to preserve both the local graph structure and the similarity between node features. Results: We studied the representation of transcriptional, protein-protein and genetic interaction networks in E. Coli and mouse using graph neural networks. We found that such representations explain a large proportion of variation in gene expression data, and that using gene expression data as node features improves the reconstruction of the graph from the embedding. We further proposed a new end-to-end graph feature auto-encoder which is trained on the feature reconstruction task, and showed that it performs better at predicting unobserved node features than auto-encoders that are trained on the graph reconstruction task before learning to predict node features. When applied to the problem of imputing missing data in single-cell RNAseq data, our graph feature auto-encoder outperformed a state-of-the-art imputation method that does not use protein interaction information, showing the benefit of integrating biological networks and omics data using graph representation learning.

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