Kitani Akihiro, Matsui Yusuke
Biomedical and Health Informatics Unit, Department of Integrated Health Science, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Institute for Glyco-core Research (iGCORE), Nagoya University, 461-8673 Nagoya, Aichi, Japan.
bioRxiv. 2024 Aug 26:2024.08.25.609610. doi: 10.1101/2024.08.25.609610.
Alzheimer's disease (AD) is an important research topic. While amyloid plaques and neurofibrillary tangles are hallmark pathological features of AD, cognitive resilience (CR) is a phenomenon where cognitive function remains preserved despite the presence of these pathological features. This study aimed to construct and compare predictive machine learning models for CR scores using RNA-seq data from the Religious Orders Study and Memory and Aging Project (ROSMAP) and Mount Sinai Brain Bank (MSBB) cohorts. We evaluated support vector regression (SVR), random forest, XGBoost, linear, and transformer-based models. The SVR model exhibited the best performance, with contributing genes identified using Shapley additive explanations (SHAP) scores, providing insights into biological pathways associated with CR. Finally, we developed a tool called the resilience gene analyzer (REGA), which visualizes SHAP scores to interpret the contributions of individual genes to CR. REGA is available at https://igcore.cloud/GerOmics/REsilienceGeneAnalyzer/.
阿尔茨海默病(AD)是一个重要的研究课题。虽然淀粉样斑块和神经原纤维缠结是AD的标志性病理特征,但认知弹性(CR)是一种尽管存在这些病理特征但认知功能仍得以保留的现象。本研究旨在使用来自宗教团体研究与记忆与衰老项目(ROSMAP)和西奈山脑库(MSBB)队列的RNA测序数据构建并比较用于CR评分的预测性机器学习模型。我们评估了支持向量回归(SVR)、随机森林、XGBoost、线性和基于Transformer的模型。SVR模型表现出最佳性能,使用Shapley加法解释(SHAP)分数确定了贡献基因,从而深入了解与CR相关的生物学途径。最后,我们开发了一种名为弹性基因分析仪(REGA)的工具,它可视化SHAP分数以解释单个基因对CR的贡献。REGA可在https://igcore.cloud/GerOmics/REsilienceGeneAnalyzer/获取。