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Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks

机译:使用贝叶斯网络发现阿尔茨海默氏症遗传生物标记

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摘要

Single nucleotide polymorphisms (SNPs) contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer's disease (AD). Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS) data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA) studies. New SNP biomarkers were observed to be significantly associated with Alzheimer's disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naïve Bayes and tree augmented naïve Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naïve Bayes, respectively.
机译:单核苷酸多态性(SNP)贡献了人类基因组的大部分遗传变异。 SNP与许多复杂和常见的疾病如阿尔茨海默氏病(AD)相关。在不同基因座处发现SNP生物标记物可以改善这些疾病的早期诊断和治疗。贝叶斯网络为表示基因或单个SNP之间的相互作用提供了一种可理解的模块化框架。在这里,不同的贝叶斯网络结构学习算法已应用于全基因组测序(WGS)数据中,以检测因果AD SNP和基因-SNP相互作用。我们关注与AD相关的前十个基因的多态性,并通过全基因组关联(GWA)研究进行了鉴定。观察到新的SNP生物标志物与阿尔茨海默氏病显着相关。这些SNP为rs7530069,rs113464261,rs114506298,rs73504429,rs7929589,rs76306710和rs668134。获得的结果证明了使用BN以可接受的准确性识别AD因果SNP的有效性。结果保证了基于马尔可夫毯式方法检测的SNP集与AD疾病有很强的关联,并且比朴素贝叶斯和树木增强朴素贝叶斯都具有更好的性能。最小的增强马尔可夫毯子的准确度达到66.13%,灵敏度达到88.87%,而朴素贝叶斯分别为61.58%和59.43%。

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