Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Bari, Italy.
Department of Physics 'Michelangelo Merlin', University of Bari 'Aldo Moro', Bari, Italy.
PLoS One. 2019 Dec 31;14(12):e0226190. doi: 10.1371/journal.pone.0226190. eCollection 2019.
Alzheimer's disease (AD) is the most common type of dementia and affects millions of people worldwide. Since complex diseases are often the result of combinations of gene interactions, microarray data and gene co-expression analysis can provide tools for addressing complexity. Our study aimed to find groups of interacting genes that are relevant in the development of AD. In this perspective, we implemented a method proposed in a previous work to detect gene communities linked to AD. Our strategy combined co-expression network analysis with the study of Shannon entropy of the betweenness. We analyzed the publicly available GSE1297 dataset, achieved from the GEO database in NCBI, containing hippocampal gene expression of 9 control and 22 AD human subjects. Co-expressed genes were clustered into different communities. Two communities of interest (composed by 72 and 39 genes) were found by calculating the correlation coefficient between communities and clinical features. The detected communities resulted stable, replicated on two independent datasets and mostly enriched in pathways closely associated with neuro-degenative diseases. A comparison between our findings and other module detection techniques showed that the detected communities were more related to AD phenotype. Lastly, the hub genes within the two communities of interest were identified by means of a centrality analysis and a bootstrap procedure. The communities of the hub genes presented even stronger correlation with clinical features. These findings and further explorations on the detected genes could shed light on the genetic aspects related with physiological aspects of Alzheimer's disease.
阿尔茨海默病(AD)是最常见的痴呆症类型,影响着全球数百万人。由于复杂疾病通常是基因相互作用的组合结果,因此微阵列数据和基因共表达分析可以提供解决复杂性的工具。我们的研究旨在寻找与 AD 发展相关的相互作用基因群。在这种情况下,我们实施了先前工作中提出的一种方法来检测与 AD 相关的基因社区。我们的策略将共表达网络分析与介数的 Shannon 熵研究相结合。我们分析了可从 NCBI 的 GEO 数据库中获得的公开 GSE1297 数据集,该数据集包含 9 名对照和 22 名 AD 人类受试者的海马基因表达。共表达基因被聚类成不同的社区。通过计算社区与临床特征之间的相关系数,发现了两个感兴趣的社区(由 72 个和 39 个基因组成)。检测到的社区是稳定的,在两个独立的数据集上得到了复制,并且主要富集在与神经退行性疾病密切相关的途径中。将我们的发现与其他模块检测技术进行比较表明,检测到的社区与 AD 表型的相关性更强。最后,通过中心性分析和引导程序确定了两个感兴趣社区中的枢纽基因。枢纽基因的社区与临床特征的相关性更强。这些发现和对检测到的基因的进一步探索可以揭示与阿尔茨海默病生理方面相关的遗传方面。