Altered expression and localization of the glutamate transporter EAAT2 is found in schizophrenia and other neuropsychiatric (major depression, MDD) and neurological disorders (amyotrophic lateral sclerosis, ALS). However, the EAAT2 interactome, the network of proteins that physically or functionally interact with EAAT2 to support its activity, has yet to be characterized in severe mental illness. We compiled a list of "core" EAAT2 interacting proteins. Using Kaleidoscope, an R-shiny application, we data mined publically available postmortem transcriptome datasets to determine whether components of the EAAT2 interactome are differentially expressed in schizophrenia and, using Reactome, identify which interactome-associated biological pathways are altered. Overall, these "look up" studies highlight region-specific, primarily frontal cortex (dorsolateral prefrontal cortex and anterior cingulate cortex), changes in the EAAT2 interactome and implicate altered metabolism pathways in schizophrenia. Pathway analyses also suggest that perturbation of components of the EAAT2 interactome in animal models of antipsychotic administration impact metabolism. Similar changes in metabolism pathways are seen in ALS, in addition to altered expression of many components of the EAAT2 interactome. However, although EAAT2 expression is altered in a postmortem MDD dataset, few other components of the EAAT2 interactome are changed. Thus, "look up" studies suggest region- and disease-relevant biological pathways related to the EAAT2 interactome that implicate glutamate reuptake perturbations in schizophrenia, while providing a useful tool to exploit "omics" datasets.

中文翻译：

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尸检和神经精神病学数据集中 EAAT2 相互作用组的生物信息学调查

在精神分裂症和其他神经精神疾病（重度抑郁症，MDD）和神经系统疾病（肌萎缩性侧索硬化症，ALS）中发现了谷氨酸转运蛋白 EAAT2 的表达和定位改变。然而，EAAT2 相互作用组，即在物理上或功能上与 EAAT2 相互作用以支持其活动的蛋白质网络，尚未在严重精神疾病中得到表征。我们编制了一份“核心”EAAT2 相互作用蛋白的列表。我们使用 R-shiny 应用程序 Kaleidoscope 对公开可用的死后转录组数据集进行数据挖掘，以确定 EAAT2 相互作用组的成分是否在精神分裂症中差异表达，并使用 Reactome 确定哪些相互作用组相关的生物通路发生了改变。总的来说，这些“查找”研究突出了特定区域，主要是额叶皮层（背外侧前额叶皮层和前扣带皮层），EAAT2 相互作用组的变化和精神分裂症中代谢途径的改变。通路分析还表明，在抗精神病药物给药的动物模型中，EAAT2 相互作用组成分的扰动会影响新陈代谢。除了 EAAT2 相互作用组的许多成分的表达改变外，在 ALS 中还观察到了代谢途径的类似变化。然而，尽管 EAAT2 表达在死后 MDD 数据集中发生了变化，但 EAAT2 相互作用组的其他组件很少发生变化。因此，“查找”研究表明与 EAAT2 相互作用组相关的区域和疾病相关生物学途径暗示精神分裂症中的谷氨酸再摄取扰动，同时提供了利用“组学”的有用工具