arXiv:2507.16801q-bio.QMcs.AI2025-07

用可解释深度学习模型解析5'UTR中调控翻译的序列功能

Decoding Translation-Related Functional Sequences in 5'UTRs Using Interpretable Deep Learning Models

  • 基于Transformer设计可处理任意长度5'UTR的模型,结合注意力聚类机制
  • 在三个数据集上预测核糖体负载量优于现有方法,准确率提升显著
  • 能识别上游AUG和Kozak等已知功能元件,适合生物机制研究者使用

理解5'非翻译区(5'UTRs)如何调控mRNA翻译对控制蛋白表达和设计有效治疗性mRNA至关重要。尽管近期深度学习模型在从5'UTR序列预测翻译效率方面展现出潜力,但大多受限于固定输入长度且可解释性差。我们提出UTR-STCNet,一种基于Transformer的架构,用于灵活且生物学合理的可变长度5'UTR建模。该模型整合了有显著性感知的令牌聚类(SATC)模块,通过显著性得分迭代将核苷酸令牌聚合成多尺度、语义有意义的单元。同时引入有显著性引导的Transformer(SGT)块,利用轻量级注意力机制捕捉局部与远端调控依赖关系。该联合架构在不截断输入或增加计算成本的前提下实现高效且可解释的建模。在三个基准数据集上的评估显示,UTR-STCNet在预测平均核糖体负载(MRL)——翻译效率的关键代理指标——方面持续优于当前最优基线。此外,模型成功恢复了已知的功能元件,如上游AUG和Kozak序列,凸显其在揭示翻译调控机制方面的潜力。

原文摘要 · Abstract (English)

Understanding how 5' untranslated regions (5'UTRs) regulate mRNA translation is critical for controlling protein expression and designing effective therapeutic mRNAs. While recent deep learning models have shown promise in predicting translational efficiency from 5'UTR sequences, most are constrained by fixed input lengths and limited interpretability. We introduce UTR-STCNet, a Transformer-based architecture for flexible and biologically grounded modeling of variable-length 5'UTRs. UTR-STCNet integrates a Saliency-Aware Token Clustering (SATC) module that iteratively aggregates nucleotide tokens into multi-scale, semantically meaningful units based on saliency scores. A Saliency-Guided Transformer (SGT) block then captures both local and distal regulatory dependencies using a lightweight attention mechanism. This combined architecture achieves efficient and interpretable modeling without input truncation or increased computational cost. Evaluated across three benchmark datasets, UTR-STCNet consistently outperforms state-of-the-art baselines in predicting mean ribosome load (MRL), a key proxy for translational efficiency. Moreover, the model recovers known functional elements such as upstream AUGs and Kozak motifs, highlighting its potential for mechanistic insight into translation regulation.

翻译调控可解释模型5'UTR深度学习

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