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

Jialin Zhang,Haoran Zhu, Yin Liu,Xiangtao Li

METHODS(2024)

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摘要
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.
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关键词
miRNA-mRNA interaction,Functional target prediction,Dynamic semantic feature
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