arXiv:2602.22850cs.LGcs.AI2026-02

提出可解释的双视角模型,精准预测DNA甲基化并发现关键序列协同机制。

MEDNA-DFM: A Dual-View FiLM-MoE Model for Explainable DNA Methylation Prediction

  • 双视角FiLM-MoE架构融合序列与结构信息,提升预测性能。
  • 在多物种数据上准确识别保守甲基化模式,验证依赖于GC含量等内在特征。
  • 通过突变实验验证GAGG与上游A-tract协同作用,适合生物机制探索者使用。

精确的计算识别DNA甲基化对理解表观遗传调控至关重要。尽管深度学习在该二分类任务中表现优异,但其“黑箱”特性限制了生物学洞察。为此,我们提出高性能模型MEDNA-DFM,并结合机制启发的信号净化算法。研究显示,MEDNA-DFM能有效捕捉保守甲基化模式,在多种物种间保持稳健区分能力。在外部独立数据集上的验证表明,模型泛化能力源于保守的内在基序(如GC含量),而非系统发育相近性。此外,所开发算法提取的基序可靠性显著高于以往研究。基于果蝇6mA案例的实证分析,我们提出“序列-结构协同”假说:GAGG核心基序与上游A-tract元件协同作用。通过体外突变实验进一步验证,任一或两者缺失均显著削弱模型识别能力。本工作不仅提供强大的甲基化预测工具,还展示了可解释深度学习如何推动方法创新与生物学假说生成。

原文摘要 · Abstract (English)

Accurate computational identification of DNA methylation is essential for understanding epigenetic regulation. Although deep learning excels in this binary classification task, its "black-box" nature impedes biological insight. We address this by introducing a high-performance model MEDNA-DFM, alongside mechanism-inspired signal purification algorithms. Our investigation demonstrates that MEDNA-DFM effectively captures conserved methylation patterns, achieving robust distinction across diverse species. Validation on external independent datasets confirms that the model's generalization is driven by conserved intrinsic motifs (e.g., GC content) rather than phylogenetic proximity. Furthermore, applying our developed algorithms extracted motifs with significantly higher reliability than prior studies. Finally, empirical evidence from a Drosophila 6mA case study prompted us to propose a "sequence-structure synergy" hypothesis, suggesting that the GAGG core motif and an upstream A-tract element function cooperatively. We further validated this hypothesis via in silico mutagenesis, confirming that the ablation of either or both elements significantly degrades the model's recognition capabilities. This work provides a powerful tool for methylation prediction and demonstrates how explainable deep learning can drive both methodological innovation and the generation of biological hypotheses.

DNA甲基化可解释模型序列分析表观遗传

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