Gene expression profiles and protein-protein interaction networks in amyotrophic lateral sclerosis patients with C9orf72 mutation.
Gene expression profiles and protein-protein interaction networks in amyotrophic lateral sclerosis patients with C9orf72 mutation.
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C9orf72 突变肌萎缩侧索硬化症患者的基因表达谱和蛋白质-蛋白质相互作用网络。
DOI：
10.1186/s13023-016-0531-y
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发表时间：
2016-11-05
影响因子：
3.7
通讯作者：
Wei DQ
中科院分区：
文献类型：
--
作者：
Kotni MK;Zhao M;Wei DQ
肌萎缩性侧索硬化症（ALS）是一种涉及神经元死亡的神经退行性疾病。如前所述，ALS与许多基因突变有关。为了探讨C9orf72突变的ALS分子机制，我们对ALS成纤维细胞和对照成纤维细胞的基因表达谱进行了生物信息学分析。具有关键功能角色的基因可以通过测量生物网络中的节点中心性来检测。在基因共表达网络中，高度连接的基因被称为候选枢纽，与关键的疾病相关途径有关。本文采用该方法寻找与ALS疾病相关的枢纽基因。Illumina HiSeq微阵列基因表达数据集GSE51684从gene expression Omnibus （GEO）数据库中检索，该数据库包括4例散发性ALS、12例家族性ALS和8例对照样本。差异表达基因（DEGs）的鉴定采用学生t检验统计方法和基因共表达网络。使用DAVID在线工具进行基因本体（GO）功能和KEGG通路富集分析。蛋白质-蛋白质相互作用（PPI）网络通过将deg映射到公开可用数据库中的蛋白质-蛋白质相互作用数据来构建，以确定deg参与的途径。使用MCODE算法将PPI相互作用网络划分为子网络，并使用Cytoscape进行分析。结果表明，DEGs的表达主要参与细胞粘附、细胞-细胞信号传导、细胞外基质区氧化石墨烯过程和局灶粘附、神经活性配体受体相互作用、细胞外基质受体相互作用。肿瘤坏死因子（Tumor necrosis factor， TNF）、内皮素1 （Endothelin 1, EDN1）、血管紧张素（Angiotensin， AGT）和许多细胞粘附分子（cell adhesion molecules， CAM）被发现为可作为ALS疾病新治疗靶点的枢纽基因。这些分析和发现有助于加深对ALS发病机制的认识，为ALS的治疗提供参考。本文的在线版本（doi:10.1186/s13023-016-0531-y）包含补充资料，仅供授权用户使用。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the death of neurons. ALS is associated with many gene mutations as previously studied. In order to explore the molecular mechanisms underlying ALS with C9orf72 mutation, gene expression profiles of ALS fibroblasts and control fibroblasts were subjected to bioinformatics analysis. Genes with critical functional roles can be detected by a measure of node centrality in biological networks. In gene co-expression networks, highly connected genes called as candidate hubs have been associated with key disease-related pathways. Herein, this method was applied to find the hub genes related to ALS disease. Illumina HiSeq microarray gene expression dataset GSE51684 was retrieved from Gene Expression Omnibus (GEO) database which included four Sporadic ALS, twelve Familial ALS and eight control samples. Differentially Expressed Genes (DEGs) were identified using the Student’s t test statistical method and gene co-expression networking. Gene ontology (GO) function and KEGG pathway enrichment analysis of DEGs were performed using the DAVID online tool. Protein-protein interaction (PPI) networks were constructed by mapping the DEGs onto protein-protein interaction data from publicly available databases to identify the pathways where DEGs are involved in. PPI interaction network was divided into subnetworks using MCODE algorithm and was analyzed using Cytoscape. The results revealed that the expression of DEGs was mainly involved in cell adhesion, cell-cell signaling, Extra cellular matrix region GO processes and focal adhesion, neuroactive ligand receptor interaction, Extracellular matrix receptor interaction. Tumor necrosis factor (TNF), Endothelin 1 (EDN1), Angiotensin (AGT) and many cell adhesion molecules (CAM) were detected as hub genes that can be targeted as novel therapeutic targets for ALS disease. These analyses and findings enhance the understanding of ALS pathogenesis and provide references for ALS therapy. The online version of this article (doi:10.1186/s13023-016-0531-y) contains supplementary material, which is available to authorized users.
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影响因子：
4.2
作者：
Kohli MA;John-Williams K;Rajbhandary R;Naj A;Whitehead P;Hamilton K;Carney RM;Wright C;Crocco E;Gwirtzman HE;Lang R;Beecham G;Martin ER;Gilbert J;Benatar M;Small GW;Mash D;Byrd G;Haines JL;Pericak-Vance MA;Züchner S
通讯作者：
Züchner S
影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
3.7
作者：
deCurtis, I;Malanchini, B
通讯作者：
Malanchini, B
DOI：
10.1084/jem.170.2.607
发表时间：
1989-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hofman FM;Hinton DR;Johnson K;Merrill JE
通讯作者：
Merrill JE
影响因子：
4.8
作者：
Ho, MCY;Lo, ACY;Chung, SK
通讯作者：
Chung, SK