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

机器学习预测和基于 tau 的筛查可识别与免疫相关的潜在阿尔茨海默病基因

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作者:Jessica Binder, Oleg Ursu, Cristian Bologa, Shanya Jiang, Nicole Maphis, Somayeh Dadras, Devon Chisholm, Jason Weick, Orrin Myers, Praveen Kumar, Jeremy J Yang, Kiran Bhaskar, Tudor I Oprea

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.

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