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miTDS: Uncovering miRNA-mRNA interactions with deep learning for functional target prediction
Jialin Zhang1, Haoran Zhu1, Yin Liu2
1School of Artificial Intelligence, Jilin University, Changchun 130012, Jilin, China.
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.
Insights
We developed miTDS, a deep learning model for identifying microRNA (miRNA) functional targets. miTDS accurately predicts miRNA-mRNA interactions, outperforming existing methods and aiding cancer research.
Area of Science:
- Genomics
- Bioinformatics
- Computational Biology
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in cancer.
- Identifying miRNA-mRNA interactions is crucial but challenging due to incomplete data and focus on known interactions.
Purpose of the Study:
- To develop a deep learning model, miTDS, for accurate identification of miRNA functional targets.
- To improve the prediction of unknown miRNA-mRNA interactions.
- To investigate aberrant RNA interactions, such as A-to-I editing, in cancer.
Main Methods:
- Developed miTDS, a deep learning model using dynamic word embeddings and transformer architecture.
- Incorporated a scoring mechanism to filter unstable sequence pairs.
- Utilized multi-scale attention and RNA-based dual-path modules for interaction analysis.
Main Results:
- miTDS demonstrated superior accuracy in predicting miRNA functional targets compared to state-of-the-art methods.
- The model was validated on datasets from MirTarbase and Diana-TarBase.
- miTDS successfully identified A-to-I RNA editing sites, offering insights into cancer suppression.
Conclusions:
- miTDS is an effective tool for predicting miRNA-mRNA functional targets.
- The model advances the understanding of miRNA-mRNA interactions and their role in cancer.
- miTDS has potential applications in identifying aberrant RNA interactions for cancer research.
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