Lee Taesic, Lee Hyunju
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
Department of Family Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
Biomedicines. 2021 Oct 23;9(11):1525. doi: 10.3390/biomedicines9111525.
Accumulating evidence has suggested a shared pathophysiology between Alzheimer's disease (AD) and cardiovascular disease (CVD). Based on genome-wide transcriptomes, specifically those of blood samples, we identify the shared disease-related signatures between AD and CVD. In addition to gene expressions in blood, the following prior knowledge were utilized to identify several candidate disease-related gene (DRG) sets: protein-protein interactions, transcription factors, disease-gene relationship databases, and single nucleotide polymorphisms. We selected the respective DRG sets for AD and CVD that show a high accuracy for disease prediction in bulk and single-cell gene expression datasets. Then, gene regulatory networks (GRNs) were constructed from each of the AD and CVD DRG sets to identify the upstream regulating genes. Using the GRNs, we identified two common upstream genes (GPBP1 and SETDB2) between the AD and CVD GRNs. In summary, this study has identified the potential AD- and CVD-related genes and common hub genes between these sets, which may help to elucidate the shared mechanisms between these two diseases.
越来越多的证据表明,阿尔茨海默病(AD)和心血管疾病(CVD)之间存在共同的病理生理学。基于全基因组转录组,特别是血液样本的转录组,我们确定了AD和CVD之间共同的疾病相关特征。除了血液中的基因表达外,还利用以下先验知识来确定几个候选疾病相关基因(DRG)集:蛋白质-蛋白质相互作用、转录因子、疾病-基因关系数据库和单核苷酸多态性。我们为AD和CVD选择了各自的DRG集,这些DRG集在批量和单细胞基因表达数据集中对疾病预测具有很高的准确性。然后,从AD和CVD的每个DRG集构建基因调控网络(GRN),以识别上游调控基因。利用这些GRN,我们在AD和CVD的GRN之间确定了两个共同的上游基因(GPBP1和SETDB2)。总之,本研究确定了潜在的AD和CVD相关基因以及这些基因集之间的共同枢纽基因,这可能有助于阐明这两种疾病之间的共同机制。