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压力与大脑转录组:从已发表实验的标准化数据中识别共性和聚类。

Stress and the brain transcriptome: Identifying commonalities and clusters in standardized data from published experiments.

机构信息

Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Jastrzebiec, Poland.

Department of Animal Behavior and Welfare, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Jastrzebiec, Poland.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20;119:110558. doi: 10.1016/j.pnpbp.2022.110558. Epub 2022 Apr 8.

Abstract

Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects. Based on the initial database containing a quarter million differential expression effect sizes representing transcripts in three species, we identified the most frequently reported genes in 223 stress-control comparisons. Additionally, the analysis considers sex, individual vulnerability and contribution of glucocorticoids. We also found an overlap between gene expression in PTSD patients and animals which indicates relevance of laboratory models for human stress response. Our analysis points to genes that, as far as we know, were not specifically tested for their role in stress response (Pllp, Arrdc2, Midn, Mfsd2a, Ccn1, Htra1, Csrnp1, Tenm4, Tnfrsf25, Sema3b, Fmo2, Adamts4, Gjb1, Errfi1, Fgf18, Galnt6, Slc25a42, Ifi30, Slc4a1, Cemip, Klf10, Tom1, Dcdc2c, Fancd2, Luzp2, Trpm1, Abcc12, Osbpl1a, Ptp4a2). Provided transcriptomic resource will be useful for guiding the new research.

摘要

转录组实验的解释受到许多问题的阻碍,包括大数据方法固有的假阳性/假阴性和基因命名法的变化。为了找到应激对大脑转录组最一致的影响,我们从 79 项应用动物模型的研究和 3 项研究创伤后应激障碍(PTSD)的人类研究中检索数据。分析的数据是从 1887 多个实验室动物和 121 个人类受试者采集的样本中使用微阵列或 RNA 测序获得的。基于包含代表三个物种中转录物的二十五万差异表达效应大小的初始数据库,我们确定了 223 个应激对照比较中最常报告的基因。此外,该分析还考虑了性别、个体易感性和糖皮质激素的贡献。我们还发现 PTSD 患者和动物的基因表达之间存在重叠,这表明实验室模型与人类应激反应有关。我们的分析指向了那些据我们所知,尚未专门针对其在应激反应中的作用进行测试的基因(Pllp、Arrdc2、Midn、Mfsd2a、Ccn1、Htra1、Csrnp1、Tenm4、Tnfrsf25、Sema3b、Fmo2、Adamts4、Gjb1、Errfi1、Fgf18、Galnt6、Slc25a42、Ifi30、Slc4a1、Cemip、Klf10、Tom1、Dcdc2c、Fancd2、Luzp2、Trpm1、Abcc12、Osbpl1a、Ptp4a2)。提供的转录组资源将有助于指导新的研究。

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