End-to-end interpretable disease–gene association prediction

计算机科学 异构网络 图形 基因调控网络 机器学习 人工智能 联想(心理学) 计算生物学 基因 数据挖掘 理论计算机科学 遗传学 生物 电信 哲学 基因表达 无线网络 认识论 无线
作者
Yang Li,Zihou Guo,Keqi Wang,Xin Gao,Guohua Wang
出处
期刊:Briefings in Bioinformatics [Oxford University Press]
卷期号:24 (3) 被引量:21
标识
DOI:10.1093/bib/bbad118
摘要

Abstract Identifying disease–gene associations is a fundamental and critical biomedical task towards understanding molecular mechanisms, the diagnosis and treatment of diseases. It is time-consuming and expensive to experimentally verify causal links between diseases and genes. Recently, deep learning methods have achieved tremendous success in identifying candidate genes for genetic diseases. The gene prediction problem can be modeled as a link prediction problem based on the features of nodes and edges of the gene–disease graph. However, most existing researches either build homogeneous networks based on one single data source or heterogeneous networks based on multi-source data, and artificially define meta-paths, so as to learn the network representation of diseases and genes. The former cannot make use of abundant multi-source heterogeneous information, while the latter needs domain knowledge and experience when defining meta-paths, and the accuracy of the model largely depends on the definition of meta-paths. To address the aforementioned challenges above bottlenecks, we propose an end-to-end disease–gene association prediction model with parallel graph transformer network (DGP-PGTN), which deeply integrates the heterogeneous information of diseases, genes, ontologies and phenotypes. DGP-PGTN can automatically and comprehensively capture the multiple latent interactions between diseases and genes, discover the causal relationship between them and is fully interpretable at the same time. We conduct comprehensive experiments and show that DGP-PGTN outperforms the state-of-the-art methods significantly on the task of disease–gene association prediction. Furthermore, DGP-PGTN can automatically learn the implicit relationship between diseases and genes without manually defining meta paths.
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