arXiv:2605.10541cs.AIcs.LG2026-05

融合序列与图结构,提升表观遗传年龄预测精度

Bridging Sequence and Graph Structure for Epigenetic Age Prediction

论文配图:Bridging Sequence and Graph Structure for Epigenetic Age Prediction
图 1 · 摘自论文原文
  • 用序列特征动态调制甲基化信号,再进行图卷积
  • 测试MAE达3.149年,比最强基线提升12.8%
  • 适合关注生物可解释性的表观遗传研究者

基于DNA甲基化的表观遗传钟已成为估算生物年龄的强大工具,广泛应用于衰老研究、年龄相关疾病和长寿科学。尽管机器学习方法在表观遗传年龄预测中取得了进展,涵盖正则化线性回归、深度前馈网络、残差架构和图神经网络,但现有方法均未在统一框架内联合建模共甲基化图结构与位点特异性DNA序列上下文。本文提出一种统一的序列-图集成框架,通过轻量级门控调制机制,整合八维DNA序列统计特征,自适应地根据序列决定的生物学重要性调整每个位点的甲基化信号,再进行图卷积。在3,707个血液甲基化样本上评估,测试MAE为3.149年,比最强的图基基线提升12.8%。生物启发的统计特征优于基于CNN的序列编码,表明在该数据场景下手工设计的序列特征比端到端学习的表示更有效。后处理可解释性分析发现,CpG密度和局部腺嘌呤频率随年龄变化的重要性发生转移,与已知的衰老相关高甲基化机制一致。代码已公开于https://github.com/yaoli2022/graphage-seq。

原文摘要 · Abstract (English)

Epigenetic clocks based on DNA methylation have emerged as powerful tools for estimating biological age, with broad applications in aging research, age-related disease studies, and longevity science. Despite advances across machine learning approaches to epigenetic age prediction, spanning penalised linear regression, deep feedforward networks, residual architectures, and graph neural networks, no existing method jointly models co-methylation graph structure and site-specific DNA sequence context within a unified framework. We propose a unified sequence--graph integration framework for epigenetic age prediction that addresses this gap, integrating eight-dimensional DNA sequence statistical features through a lightweight gated modulation mechanism that adaptively scales each site's methylation signal according to its sequence-determined biological relevance prior to graph convolution. Evaluated on 3,707 blood methylation samples against a comprehensive set of baselines, our method achieves a test MAE of 3.149 years, a 12.8\% improvement over the strongest graph-based baseline. Biologically informed statistical features outperform CNN-based sequence encoding, demonstrating that handcrafted sequence features are more effective than end-to-end learned representations in this data regime. Post-hoc interpretability analysis identifies CpG density and local adenine frequency as features with age-dependent importance shifts, consistent with known mechanisms of age-related hypermethylation at CpG-dense promoter regions. Our code is at https://github.com/yaoli2022/graphage-seq.

表观遗传图神经网络年龄预测

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