基于生物信息学筛选脓毒症中性粒细胞活化的关键基因

目的基于生物信息学筛选脓毒症中性粒细胞活化的关键基因。 方法从GEO数据库中下载4个成人脓毒症芯片数据集(GSE69528、GSE28750、GSE57065、GSE95233),进行差异表达基因(DEG)筛选。基因本体论(GO)分析DEG,STRING数据库构建蛋白互作网络,Cytoscape软件提取关键基因,CIBERSORT算法估算数据集中的免疫细胞表达水平,ROC曲线评价关键基因对脓毒症患者的诊断价值。取儿童脓毒症相关芯片数据集(GSE66099)进行验证。 结果4个成人脓毒症数据集筛选出299个重叠DEG,其中112个基因上调,187个基因下调。GO主要富集于中性粒细胞活化、中性粒细胞脱颗粒、肽酶调节活性、糖胺聚糖结合、特殊颗粒、囊泡腔等。筛选出脓毒症中性粒细胞活化的关键基因10个,在脓毒症中表达水平均上调,ROC曲线下面积均大于0.7,具有较好的诊断价值。儿童脓毒症数据集验证结果与成人脓毒症数据集结果一致。 结论基于生物信息学方法筛选出脓毒症中性粒细胞活化相关的10个关键基因,为脓毒症的早期诊断、预后判断及治疗提供了潜在新靶点。

Screening key genes of neutrophil activation in sepsis based on biological information

AimTo screen the key genes of neutrophil activation in sepsis based on bioinformatics. MethodsFour adult sepsis microarray datasets (GSE69528, GSE28750, GSE57065, GSE95233) were downloaded from GEO database and screened for differentially expressed genes (DEG). Gene ontology(GO) was used to analyze DEG, STRING database was used to construct protein-protein interaction network, Cytoscape software was used to extract key genes, CIBERSORT algorithm was used to estimate immune cell expression levels, and ROC curve was used to evaluate the diagnostic value of key genes in sepsis patients. The child sepsis related chip dataset (GSE66099) was used for verification. ResultsFrom the four adult sepsis datasets, 299 overlapping DEGs were screened, with 112 up-regulated genes and 187 down-regulated genes. GO is mainly enriched in neutrophil activation, neutrophil degranulation, peptidyase regulatory activity, glycosaminoglycan binding, special particles, vesicular cavity, etc. 10 key genes of neutrophil activation in sepsis were screened, and their expression levels were all up-regulated in sepsis. The areas under ROC curve were all greater than 0.7, which showed good diagnostic value. The validation results of the pediatric sepsis dataset were consistent with those of the adult sepsis dataset. ConclusionBased on bioinformatics, 10 key genes related to neutrophil activation in sepsis were selected, which provided potential new targets for early diagnosis, prognosis and treatment of sepsis.