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SRG-Vote:通过嵌入和长短期记忆网络集成预测微小RNA-基因关系

SRG-Vote: Predicting Mirna-Gene Relationships via Embedding and LSTM Ensemble.

作者信息

Xie Weidun, Zheng Zetian, Zhang Weitong, Huang Lei, Lin Qiuzhen, Wong Ka-Chun

出版信息

IEEE J Biomed Health Inform. 2022 Aug;26(8):4335-4344. doi: 10.1109/JBHI.2022.3169542. Epub 2022 Aug 11.

Abstract

Targeted therapy for one for a set of genes has made it possible to apply precision medicine for different patients due to the existence of tumor heterogeneity. However, how to regulate those genes are still problematic. One of the natural regulators of genes is microRNAs. Thus, a better understanding of the miRNA-gene interaction mechanism might contribute to future diagnosis, prevention, and cancer therapy. The interactions between microRNA and genes play an essential role in molecular genetics. The in-vivo experiments validating the relationships between them are time-consuming, money-costly, and labor-intensive. With the development of high-throughput technology, we dealt with tons of biological data. However, extracting features from tremendous raw data and making a mathematical model is still a challenging topic. Machine learning and deep learning algorithms have become powerful tools in dealing with biological data. Inspired by this, in this paper, we propose a model that combines features/embedding extraction methods, deep learning algorithms, and a voting system. We leverage doc2vec to generate sequential embedding from molecular sequences. The role2vec, GCN, and GMM for geometrical embedding were generated from the complex network from similarity and pair-wise datasets. For the deep learning algorithms, we leveraged LSTM and Bi-LSTM according to different embedding and features. Finally, we adopted a voting system to balance results from different data sources. The results have shown that our voting system could achieve a higher AUC than the existing benchmark. The case studies demonstrate that our model could reveal potential relationships between miRNAs and genes. The source code, features, and predictive results can be downloaded at https://github.com/Xshelton/SRG-vote.

摘要

由于肿瘤异质性的存在,针对一组基因的靶向治疗使得针对不同患者应用精准医学成为可能。然而,如何调控这些基因仍然存在问题。基因的天然调节因子之一是微小RNA(microRNA)。因此,更好地理解微小RNA与基因的相互作用机制可能有助于未来的诊断、预防和癌症治疗。微小RNA与基因之间的相互作用在分子遗传学中起着至关重要的作用。验证它们之间关系的体内实验既耗时、成本高又 labor-intensive。随着高通量技术的发展,我们处理了大量的生物数据。然而,从海量的原始数据中提取特征并建立数学模型仍然是一个具有挑战性的课题。机器学习和深度学习算法已成为处理生物数据的强大工具。受此启发,在本文中,我们提出了一个结合特征/嵌入提取方法、深度学习算法和投票系统的模型。我们利用doc2vec从分子序列生成序列嵌入。从相似性和成对数据集的复杂网络中生成用于几何嵌入的role2vec、GCN和GMM。对于深度学习算法,我们根据不同的嵌入和特征利用了LSTM和双向LSTM。最后,我们采用投票系统来平衡来自不同数据源的结果。结果表明,我们的投票系统可以实现比现有基准更高的AUC。案例研究表明,我们的模型可以揭示微小RNA与基因之间的潜在关系。源代码、特征和预测结果可在https://github.com/Xshelton/SRG-vote下载。

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