Chitrala Kumaraswamy Naidu, Nagarkatti Prakash, Nagarkatti Mitzi
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
PLoS One. 2016 Dec 20;11(12):e0168404. doi: 10.1371/journal.pone.0168404. eCollection 2016.
Post-traumatic stress disorder is one of the common mental ailments that is triggered by exposure to traumatic events. Till date, the molecular factors conferring risk to the development of PTSD is not well understood. In this study, we have conducted a meta-analysis followed by hierarchical clustering and functional enrichment, to uncover the potential molecular networks and critical genes which play an important role in PTSD. Two datasets of expression profiles from Peripheral Blood Mononuclear Cells from 62 control samples and 63 PTSD samples were included in our study. In PTSD samples of GSE860 dataset, we identified 26 genes informative when compared with Post-deploy PTSD condition and 58 genes informative when compared with Pre-deploy and Post-deploy PTSD of GSE63878 dataset. We conducted the meta-analysis using Fisher, roP, Stouffer, AW, SR, PR and RP methods in MetaDE package. Results from the rOP method of MetaDE package showed that among these genes, the following showed significant changes including, OR2B6, SOX21, MOBP, IL15, PTPRK, PPBPP2 and SEC14L5. Gene ontology analysis revealed enrichment of these significant PTSD-related genes for cell proliferation, DNA damage and repair (p-value ≤ 0.05). Furthermore, interaction network analysis was performed on these 7 significant genes. This analysis revealed highly connected functional interaction networks with two candidate genes, IL15 and SEC14L5 highly enriched in networks. Overall, from these results, we concluded that these genes can be recommended as some of the potential targets for PTSD.
创伤后应激障碍是由暴露于创伤性事件引发的常见精神疾病之一。迄今为止,导致创伤后应激障碍发生风险的分子因素尚未得到充分了解。在本研究中,我们进行了荟萃分析,随后进行分层聚类和功能富集分析,以揭示在创伤后应激障碍中起重要作用的潜在分子网络和关键基因。我们的研究纳入了来自62个对照样本和63个创伤后应激障碍样本的外周血单核细胞表达谱的两个数据集。在GSE860数据集的创伤后应激障碍样本中,与部署后创伤后应激障碍状况相比,我们鉴定出26个信息丰富的基因,与GSE63878数据集的部署前和部署后创伤后应激障碍相比,鉴定出58个信息丰富的基因。我们使用MetaDE软件包中的Fisher、roP、Stouffer、AW、SR、PR和RP方法进行了荟萃分析。MetaDE软件包的roP方法结果显示,在这些基因中,以下基因显示出显著变化,包括OR2B6、SOX21、MOBP、IL15、PTPRK、PPBPP2和SEC14L5。基因本体分析揭示了这些与创伤后应激障碍显著相关的基因在细胞增殖、DNA损伤和修复方面的富集(p值≤0.05)。此外,对这7个显著基因进行了相互作用网络分析。该分析揭示了高度连接的功能相互作用网络,其中两个候选基因IL15和SEC14L5在网络中高度富集。总体而言,从这些结果中,我们得出结论,这些基因可被推荐为创伤后应激障碍的一些潜在靶点。