Identification of differentially expressed genes and regulatory relationships in Huntington's disease by bioinformatics analysis.
Identification of differentially expressed genes and regulatory relationships in Huntington's disease by bioinformatics analysis.
复制标题
通过生物信息学分析鉴定亨廷顿病差异表达基因及调控关系
DOI：
10.3892/mmr.2018.8410
复制
发表时间：
2018-03
影响因子：
3.4
通讯作者：
Cong S
中科院分区：
文献类型：
--
作者：
Dong X;Cong S
亨廷顿病 (HD) 是一种遗传性进行性神经退行性疾病，由亨廷顿 (HTT) 基因的 CAG 扩增引起。已经提出了 HD 中生物过程的各种功能障碍。然而，目前HD的确切发病机制尚不完全清楚。本研究旨在利用基因表达的计算生物信息学分析来探讨 HD 的发病机制。从Gene Expression Omnibus下载GSE11358，预测突变HTT敲入细胞模型STHdhQ111/Q111中的差异表达基因（DEG）。使用 R 中的 limma 包筛选 HD 和对照样本之间的 DEG。使用数据库进行注释、可视化和集成发现软件进行功能和通路富集分析。通过检索相互作用基因的搜索工具建立了蛋白质-蛋白质相互作用（PPI）网络，并通过 Cytoscape 进行可视化。利用 MCODE 对 PPI 网络进行模块分析。总共鉴定了 471 个 DEG，包括核糖核酸酶 A 家族成员 4 (RNA酶4)。此外，还确定了 41 个显着丰富的京都基因和基因组百科全书途径，以及几个重要的基因本体术语（包括细胞因子-细胞因子受体相互作用和胞质 DNA 传感）。 PPI 网络中总共确定了 18 个重要模块。此外，还发现了一种新的转录调控关系，即信号转导子和转录激活子 3 (STAT3)，在 HD 中受 miRNA-124 调控。总之，18个关键基因的失调可能导致HD的发生。 RNASE4、STAT3 和 miRNA-124 可能与 HD 的病理机制具有调节相关性。
Huntington's disease (HD) is an inherited, progressive neurodegenerative disease caused by a CAG expansion in the huntingtin (HTT) gene; various dysfunctions of biological processes in HD have been proposed. However, at present the exact pathogenesis of HD is not fully understood. The present study aimed to explore the pathogenesis of HD using a computational bioinformatics analysis of gene expression. GSE11358 was downloaded from the Gene Expression Omnibus andthe differentially expressed genes (DEGs) in the mutant HTT knock-in cell model STHdhQ111/Q111 were predicted. DEGs between the HD and control samples were screened using the limma package in R. Functional and pathway enrichment analyses were conducted using the database for annotation, visualization and integrated discovery software. A protein-protein interaction (PPI) network was established by the search tool for the retrieval of interacting genes and visualized by Cytoscape. Module analysis of the PPI network was performed utilizing MCODE. A total of 471 DEGs were identified, including ribonuclease A family member 4 (RNASE4). In addition, 41 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways, as well as several significant Gene Ontology terms (including cytokine-cytokine receptor interaction and cytosolic DNA-sensing) were identified. A total of 18 significant modules were identified from the PPI network. Furthermore, a novel transcriptional regulatory relationship was identified, namely signal transducer and activator of transcription 3 (STAT3), which is regulated by miRNA-124 in HD. In conclusion, deregulation of 18 critical genes may contribute to the occurrence of HD. RNASE4, STAT3, and miRNA-124 may have a regulatory association with the pathological mechanisms in HD.
登录
查看更多内容
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
0.9
作者：
Guo, Wenge;Rao, M. Bhaskara
通讯作者：
Rao, M. Bhaskara
影响因子：
5.6
作者：
Hofmann-Apitius M;Ball G;Gebel S;Bagewadi S;de Bono B;Schneider R;Page M;Kodamullil AT;Younesi E;Ebeling C;Tegnér J;Canard L
通讯作者：
Canard L
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group
影响因子：
3.7
作者：
Fu MH;Li CL;Lin HL;Tsai SJ;Lai YY;Chang YF;Cheng PH;Chen CM;Yang SH
通讯作者：
Yang SH