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机器学习预测和基于 Tau 的筛选鉴定出与免疫相关的潜在阿尔茨海默病基因。

Machine learning prediction and tau-based screening identifies potential Alzheimer's disease genes relevant to immunity.

机构信息

Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.

Computational and Structural Chemistry, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.

出版信息

Commun Biol. 2022 Feb 11;5(1):125. doi: 10.1038/s42003-022-03068-7.

Abstract

With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand the ever-growing omics data to enhance early diagnosis, map complex disease networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph and evidence paths transformed into vectors by metapath matching. We extracted features between specific genes and diseases, then trained and optimized our model using XGBoost, termed MPxgb(AD). To determine our MPxgb(AD) prediction performance, we examined the top twenty predicted genes through an experimental screening pipeline. Our analysis identified potential AD risk genes: FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2. FRRS1 and FAM92B are considered dark genes, while CTRAM, SCGB3A1, and TMEFF2 are connected to TREM2-TYROBP, IL-1β-TNFα, and MTOR-APP AD-risk nodes, suggesting relevance to the pathogenesis of AD.

摘要

随着全球对阿尔茨海默病(AD)和相关疾病研究资金的增加,大量数据正在产生。一些研究采用机器学习方法来理解不断增长的组学数据,以增强早期诊断、绘制复杂疾病网络或发现潜在的药物靶点。我们描述了基于目标中央资源数据库蛋白质知识图和通过元路径匹配转换为向量的证据路径的结果。我们提取了特定基因和疾病之间的特征,然后使用 XGBoost 对我们的模型进行了训练和优化,称为 MPxgb(AD)。为了确定我们的 MPxgb(AD)预测性能,我们通过实验筛选管道检查了前二十个预测基因。我们的分析确定了潜在的 AD 风险基因:FRRS1、CTRAM、SCGB3A1、FAM92B/CIBAR2 和 TMEFF2。FRRS1 和 FAM92B 被认为是暗基因,而 CTRAM、SCGB3A1 和 TMEFF2 与 TREM2-TYROBP、IL-1β-TNFα 和 MTOR-APP AD 风险节点相关,表明与 AD 的发病机制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c29b/8837797/58d185072fb6/42003_2022_3068_Fig1_HTML.jpg

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