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Integrated identification of key genes and pathways in Alzheimer’s disease via comprehensive bioinformatical analyses
Hereditas ( IF 2.7 ) Pub Date : 2019-07-16 , DOI: 10.1186/s41065-019-0101-0
Tingting Yan 1 , Feng Ding 1 , Yan Zhao 1
Affiliation  

BackgroundAlzheimer’s disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.MethodsGene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree≥10 (for hippocampus tissues) and ≥ 8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA).Results251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD.ConclusionsThrough GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.

中文翻译:

通过综合生物信息学分析综合鉴定阿尔茨海默病的关键基因和通路

背景阿尔茨海默病(Alzheimer's disease,AD)已知由多种因素引起,而AD的发病机制和发展与遗传因素密切相关。现有对 AD 分子机制的理解仍然不完整。方法来自后现代大脑的基因表达数据 (GSE48350) 是从基因表达综合 (GEO) 数据库中提取的。差异表达基因 (DEG) 来自 AD 患者和健康对照之间的海马和内嗅皮层区域,并通过 Morpheus 检测。通过 Cytoscape 进行功能富集分析,包括基因本体论 (GO) 和 DEG 通路分析,然后构建蛋白质-蛋白质相互作用 (PPI) 网络。使用以下标准筛选集线器蛋白:节点度≥10(海马组织)和≥8(内嗅皮质组织)。分子复合物检测 (MCODE) 用于过滤重要的簇。加州大学圣克鲁斯分校 (UCSC) 和 RNA 结合蛋白特异性数据库 (RBPDB) 被用来鉴定长链非编码 RNA (lncRNA) 的 RNA 结合蛋白。结果 251 和 74 个基因被鉴定为 DEG,其中分别由海马和内嗅皮质中的 56 和 16 个上调基因和 195 和 58 个下调基因组成。生物学分析表明,与记忆、跨膜转运、突触传递、神经元存活、药物代谢、离子稳态和信号转导相关的生物学过程和通路在这些基因中富集。11个基因被鉴定为海马和内嗅皮层中枢基因,3个中枢基因被鉴定为参与AD病理学的新候选基因。进一步筛选出与AD密切相关的3个lncRNA。结论通过GO富集分析、通路分析和PPI分析,我们在系统生物学水平上全面解读了AD的发病机制,发现了3个新候选基因和3个新候选基因。 lncRNAs被鉴定为参与AD病理学的新的和潜在的候选者。这项研究的结果可以为理解 AD 的致病机制和潜在的新治疗靶点提供综合见解。结参加 AD 病理学的候选人。这项研究的结果可以为理解 AD 的致病机制和潜在的新治疗靶点提供综合见解。结参加 AD 病理学的候选人。这项研究的结果可以为理解 AD 的致病机制和潜在的新治疗靶点提供综合见解。3个新的候选基因和3个lncRNA被鉴定为参与AD病理学的新的和潜在的候选基因。这项研究的结果可以为理解 AD 的致病机制和潜在的新治疗靶点提供综合见解。3个新的候选基因和3个lncRNA被鉴定为参与AD病理学的新的和潜在的候选基因。这项研究的结果可以为理解 AD 的致病机制和潜在的新治疗靶点提供综合见解。
更新日期:2019-07-16
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