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通过基因表达谱分析鉴定与连续性创伤性脓毒症相关的基因

Identification of genes related to consecutive trauma-induced sepsis via gene expression profiling analysis.

作者信息

Dong Lei, Li Hongwei, Zhang Shunli, Su Long

机构信息

Intensive Care Unit Department of Pediatrics, Jining NO.1 People's Hospital, Jining City, Shandong Province, China.

出版信息

Medicine (Baltimore). 2018 Apr;97(15):e0362. doi: 10.1097/MD.0000000000010362.

Abstract

We aimed to identify crucial genes relevant to the development of consecutive trauma-induced sepsis.A microarray dataset was used to identify genes differentially expressed between peripheral blood samples from consecutive traumatized patients complicated with sepsis and not complicated with sepsis. The dataset GSE12624 was obtained from Gene Expression Omnibus, containing 34 peripheral blood samples from consecutive traumatized patients complicated by sepsis and 36 consecutive traumatized controls. The differentially expressed genes (DEGs) were identified using Linear Models for Microarray Data package. Then, gene ontology (GO) enrichment analysis for DEGs was performed by Onto-Express. Subsequently, the protein-protein interaction (PPI) network was constructed and pathway enrichment analysis was performed by Search Tool for the Retrieval of Interacting Genes (STRING). Furthermore, protein complexes in the PPI network were predicted by ClusterONE and validated through GO and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and protein domain analysis.Totally, 446 upregulated and 447 downregulated DEGs were identified. Some DEGs were related to acyl-CoA binding (eg, ACBD6), chromosome, and centromeric region (eg, CENPN). In the PPI network, some DEGs were enriched in renin-angiotensin system (RAS, eg, AGTR1 and AGTR2). Three predicted protein complexes were validated in the PPI network. Some genes composing protein complex A were associated with cell proliferation (eg, CDC20, CCNB1, MCM4, RPA2, and PRIM2), and several genes composing protein complex F were implicated in regulation of actin cytoskeleton (eg, PFN2, ARPC2, and WASL).The results suggest that those DEGs may be crucial in the etiology of consecutive trauma-induced sepsis, and they are expected to be therapeutic targets.

摘要

我们旨在识别与连续性创伤性脓毒症发生发展相关的关键基因。使用一个微阵列数据集来识别连续性创伤且并发脓毒症的患者与未并发脓毒症的患者外周血样本之间差异表达的基因。数据集GSE12624取自基因表达综合数据库,包含34例连续性创伤且并发脓毒症患者的外周血样本以及36例连续性创伤对照样本。使用微阵列数据线性模型软件包识别差异表达基因(DEGs)。然后,通过Onto-Express对DEGs进行基因本体(GO)富集分析。随后,构建蛋白质-蛋白质相互作用(PPI)网络,并通过检索相互作用基因的搜索工具(STRING)进行通路富集分析。此外,通过ClusterONE预测PPI网络中的蛋白质复合物,并通过GO和京都基因与基因组百科全书通路富集分析以及蛋白质结构域分析进行验证。总共识别出446个上调的DEGs和447个下调的DEGs。一些DEGs与酰基辅酶A结合(如ACBD6)、染色体和着丝粒区域(如CENPN)相关。在PPI网络中,一些DEGs富集于肾素-血管紧张素系统(RAS,如AGTR1和AGTR2)。在PPI网络中验证了三个预测的蛋白质复合物。组成蛋白质复合物A的一些基因与细胞增殖相关(如CDC20、CCNB1、MCM4、RPA2和PRIM2),组成蛋白质复合物F的几个基因与肌动蛋白细胞骨架的调节有关(如PFN2、ARPC2和WASL)。结果表明,这些DEGs可能在连续性创伤性脓毒症的病因学中起关键作用,有望成为治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb6/5908625/569d20aac6e4/medi-97-e0362-g002.jpg

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