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miTDS:利用深度学习揭示 miRNA-mRNA 相互作用,进行功能靶标预测。

miTDS: Uncovering miRNA-mRNA interactions with deep learning for functional target prediction.

机构信息

School of Artificial Intelligence, Jilin University, Changchun 130012, Jilin, China.

China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.

出版信息

Methods. 2024 Mar;223:65-74. doi: 10.1016/j.ymeth.2024.01.011. Epub 2024 Jan 26.

Abstract

MicroRNAs (miRNAs) are vital in regulating gene expression through binding to specific target sites on messenger RNAs (mRNAs), a process closely tied to cancer pathogenesis. Identifying miRNA functional targets is essential but challenging, due to incomplete genome annotation and an emphasis on known miRNA-mRNA interactions, restricting predictions of unknown ones. To address those challenges, we have developed a deep learning model based on miRNA functional target identification, named miTDS, to investigate miRNA-mRNA interactions. miTDS first employs a scoring mechanism to eliminate unstable sequence pairs and then utilizes a dynamic word embedding model based on the transformer architecture, enabling a comprehensive analysis of miRNA-mRNA interaction sites by harnessing the global contextual associations of each nucleotide. On this basis, miTDS fuses extended seed alignment representations learned in the multi-scale attention mechanism module with dynamic semantic representations extracted in the RNA-based dual-path module, which can further elucidate and predict miRNA and mRNA functions and interactions. To validate the effectiveness of miTDS, we conducted a thorough comparison with state-of-the-art miRNA-mRNA functional target prediction methods. The evaluation, performed on a dataset cross-referenced with entries from MirTarbase and Diana-TarBase, revealed that miTDS surpasses current methods in accurately predicting functional targets. In addition, our model exhibited proficiency in identifying A-to-I RNA editing sites, which represents an aberrant interaction that yields valuable insights into the suppression of cancerous processes.

摘要

微小 RNA(miRNA)通过与信使 RNA(mRNA)上的特定靶位点结合来调节基因表达,这一过程与癌症发病机制密切相关。鉴定 miRNA 的功能靶标至关重要,但具有挑战性,这是由于不完全的基因组注释和对已知 miRNA-mRNA 相互作用的重视,限制了对未知 miRNA-mRNA 相互作用的预测。为了解决这些挑战,我们开发了一种基于 miRNA 功能靶标识别的深度学习模型,命名为 miTDS,用于研究 miRNA-mRNA 相互作用。miTDS 首先采用评分机制消除不稳定的序列对,然后利用基于转换器架构的动态词嵌入模型,通过利用每个核苷酸的全局上下文关联,对 miRNA-mRNA 相互作用位点进行全面分析。在此基础上,miTDS 将多尺度注意力机制模块中学习到的扩展种子对齐表示与基于 RNA 的双路径模块中提取的动态语义表示融合在一起,从而进一步阐明和预测 miRNA 和 mRNA 的功能和相互作用。为了验证 miTDS 的有效性,我们与最先进的 miRNA-mRNA 功能靶标预测方法进行了全面比较。在与 MirTarbase 和 Diana-TarBase 条目交叉引用的数据集上进行的评估表明,miTDS 在准确预测功能靶标方面优于现有方法。此外,我们的模型还擅长识别 A-to-I RNA 编辑位点,这代表了一种异常的相互作用,为抑制癌症过程提供了有价值的见解。

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