arXiv:2605.20747q-bio.GNcs.LG2026-05

用多模态机器学习挖掘长链非编码RNA与糖尿病的关联,揭示关键分子特征。

Multi-Modal Machine Learning for Population- and Subject-Specific lncRNA-Type 2 Diabetes Association Analysis

论文配图:Multi-Modal Machine Learning for Population- and Subject-Specific lncRNA-Type 2 Diabetes Association Analysis
图 1 · 摘自论文原文
  • 整合表达、结构和序列特征,构建多模态分析框架
  • 发现GAS5、XIST等在两组人群中的表达与序列特征相关
  • 通过可解释性分析定位MEG3为核心调控因子,适合精准医疗研究

长链非编码RNA(lncRNA)在慢性病如2型糖尿病(T2D)发病机制中起重要作用。本研究分析了10个文献报道的T2D相关lncRNA:MALAT1、MEG3、MIAT、ANRIL、GAS5、KCNQ1OT1、H19、BCYRN1、XIST和HOTAIR,基于两个独立的群体队列(RNA-seq数据)。单组学方法难以全面揭示疾病生物学,因此提出整合表达、二级结构和序列特征的多特征框架。采用8种机器学习分类器,在分层k折、留一法交叉验证(LOOCV)和重复留出法下评估性能。使用SHAP进行个体水平关联解释。第一队列中,GAS5和XIST的表达特征,以及GAS5、MEG3和ANRIL的序列特征与T2D相关;第二队列中,MALAT1表达及KCNQ1OT1、ANRIL、MEG3的序列特征相关。SHAP分析显示MEG3在两队列中均为主导因素。机器学习结果与传统统计方法一致,且提供人群与个体层面的疾病关联图谱,关联特定分子特征类型。该框架推动对T2D的机制理解,并支持基于lncRNA的精准医学发展。

原文摘要 · Abstract (English)

Long non-coding RNAs (lncRNAs) are emerging regulatory molecules implicated in chronic disease pathogenesis, including Type 2 Diabetes Mellitus (T2D). We investigated ten literature reported lncRNAs associated with T2D: MALAT1, MEG3, MIAT, ANRIL, GAS5, KCNQ1OT1, H19, BCYRN1, XIST, and HOTAIR across two independent population-based RNA-seq cohorts. Single-omics approaches provide an incomplete view of disease biology, therefore, an integrative multi-feature framework was developed, extracting expression, secondary-structure, and sequence features for each lncRNA. Eight machine learning (ML) classifiers were evaluated under stratified k-fold, leave-one-out cross-validation (LOOCV), and repeated hold-out schemes to ensure robust performance estimation. SHAP analysis was applied for subject-level association interpretation. In one cohort, GAS5 and XIST expression features, along with GAS5, MEG3, and ANRIL sequence features, were found to be associated with T2D, while MALAT1 expression and KCNQ1OT1, ANRIL, and MEG3 sequence features were found to be associated in the second cohort. MEG3 was identified by SHAP as the dominant lncRNA in both cohorts. ML results were consistent with established statistical methods while additionally providing population- and subject-level disease association profiles linked to specific molecular feature types. The proposed framework advances mechanistic understanding of T2D and supports lncRNA-based precision medicine.

lncRNA糖尿病机器学习多组学

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