Insights into TREM2 biology by network analysis of human brain gene expression data.
Insights into TREM2 biology by network analysis of human brain gene expression data.
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DOI：
10.1016/j.neurobiolaging.2013.05.001
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发表时间：
2013-12
影响因子：
4.2
通讯作者：
Ryten M
中科院分区：
文献类型：
--
作者：
Forabosco P;Ramasamy A;Trabzuni D;Walker R;Smith C;Bras J;Levine AP;Hardy J;Pocock JM;Guerreiro R;Weale ME;Ryten M
TREM2中的罕见变体导致对晚发性阿尔茨海默病的易感性。在这里，我们使用基于微阵列的表达数据，这些数据来自101名神经病理正常个体，覆盖了包括海马在内的10个大脑区域，以了解人脑中的TREM2生物学。使用网络分析，我们在人脑中检测到一个高度保存的含有TREM2的模块，表明它与小胶质细胞有关，并证明TREM2是包括海马在内的5个脑区的枢纽基因，这表明它可以驱动模块功能。使用富集分析，我们显示出显着的过度表达的基因涉及的适应性和先天免疫系统。对与TREM2具有最高连接性的基因的检查表明，它在介导小胶质细胞骨架的变化中起着关键作用，这些变化不仅是吞噬作用所必需的，而且是迁移所必需的。最重要的是，我们发现含TREM2的模块显著富集了与阿尔茨海默病、多发性硬化症和运动神经元疾病有关的基因，这意味着这些疾病共享以小胶质细胞为中心的共同途径，并且在所识别的基因中可能存在新的疾病相关基因。
Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes.
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.
影响因子：
4.4
作者：
Daws, MR;Sullam, PM;Seaman, WE
通讯作者：
Seaman, WE
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav