Zhang Junli, Cheng Yuelei, Duan Minmin, Qi Nannan, Liu Jian
Department of Emergency Medicine, Affiliated Hospital of Taishan Medical University of Shandong Province, No.706 TaiShan Street, Taishan District, Taian, 271000, China.
Department of Pediatrics, Affiliated Hospital of Taishan Medical University of Shandong Province, Taian, China.
3 Biotech. 2017 May;7(1):46. doi: 10.1007/s13205-017-0713-x. Epub 2017 Apr 25.
In this study, we integrated the gene expression data of sepsis to reveal more precise genome-wide expression signature to shed light on the pathological mechanism of sepsis. Differentially expressed genes via integrating five microarray datasets from the Gene Expression Omnibus database were obtained. The gene function and involved pathways of differentially expressed genes (DEGs) were detected by GeneCodis3. Transcription factors (TFs) targeting top 20 dysregulated DEGs (including up- and downregulated genes) were found based on the TRANSFAC. A total of 1339 DEGs were detected including 788 upregulated and 551 downregulated genes. These genes were mostly involved in DNA-dependent transcription regulation, blood coagulation, and innate immune response, pathogenic escherichia coli infection, epithelial cell signaling in helicobacter pylori infection, and chemokine signaling pathway. TFs bioinformatic analysis of 20 DEGs generated 374 pairs of TF-target gene involving 47 TFs. At last, we found that five top ten upregulated DEGs (S100A8, S100A9, S100A12, PGLYRP1 and MMP9) and three downregulated DEGs (ZNF84, CYB561A3 and BST1) were under the regulation of three hub TFs of Pax-4, POU2F1, and Nkx2-5. The identified eight DEGs may be regarded as the diagnosis marker and drug target for sepsis.
在本研究中,我们整合了脓毒症的基因表达数据,以揭示更精确的全基因组表达特征,从而阐明脓毒症的病理机制。通过整合来自基因表达综合数据库的五个微阵列数据集,获得了差异表达基因。利用GeneCodis3检测差异表达基因(DEGs)的基因功能和涉及的通路。基于TRANSFAC数据库,找到了靶向20个失调程度最高的DEGs(包括上调和下调基因)的转录因子(TFs)。共检测到1339个DEGs,其中788个上调基因和551个下调基因。这些基因主要参与DNA依赖性转录调控、血液凝固、先天免疫反应、致病性大肠杆菌感染、幽门螺杆菌感染中的上皮细胞信号传导以及趋化因子信号通路。对20个DEGs进行的TFs生物信息学分析产生了374对TF-靶基因,涉及47个TFs。最后,我们发现五个上调程度最高的前十位DEGs(S100A8、S100A9、S100A12、PGLYRP1和MMP9)和三个下调DEGs(ZNF84、CYB561A3和BST1)受Pax-4、POU2F1和Nkx2-5这三个枢纽TFs的调控。所鉴定出的八个DEGs可被视为脓毒症的诊断标志物和药物靶点。