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克罗恩病神经网络诊断模型的构建及免疫浸润特征研究

Construction of a neural network diagnostic model and investigation of immune infiltration characteristics for Crohn's disease.

作者信息

Yang Yufei, Xu Lijun, Qiao Yuqi, Wang Tianrong, Zheng Qing

机构信息

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.

出版信息

Front Genet. 2022 Sep 15;13:976578. doi: 10.3389/fgene.2022.976578. eCollection 2022.

Abstract

Crohn's disease (CD), a chronic recurrent illness, is a type of inflammatory bowel disease whose incidence and prevalence rates are gradually increasing. However, there is no universally accepted criterion for CD diagnosis. The aim of this study was to create a diagnostic prediction model for CD and identify immune cell infiltration features in CD. In this study, gene expression microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) between 178 CD and 38 control cases. Enrichment analysis of DEGs was also performed to explore the biological role of DEGs. Moreover, the "randomForest" package was applied to select core genes that were used to create a neural network model. Finally, in the training cohort, we used CIBERSORT to evaluate the immune landscape between the CD and normal groups. The results of enrichment analysis revealed that these DEGs may be involved in biological processes associated with immunity and inflammatory responses. Moreover, the top 3 hub genes in the protein-protein interaction network were IL-1β, CCL2, and CXCR2. The diagnostic model allowed significant discrimination with an area under the ROC curve of 0.984 [95% confidence interval: 0.971-0.993]. A validation cohort (GSE36807) was utilized to ensure the reliability and applicability of the model. In addition, the immune infiltration analysis indicated nine different immune cell types were significantly different between the CD and healthy control groups. In summary, this study offers a novel insight into the diagnosis of CD and provides potential biomarkers for the precise treatment of CD.

摘要

克罗恩病(CD)是一种慢性复发性疾病,属于炎症性肠病,其发病率和患病率正在逐渐上升。然而,目前尚无普遍接受的CD诊断标准。本研究的目的是建立一个CD诊断预测模型,并确定CD中的免疫细胞浸润特征。在本研究中,从基因表达综合数据库(GEO)中获取基因表达微阵列数据集。然后,我们鉴定了178例CD患者和38例对照病例之间的差异表达基因(DEG)。还对DEG进行了富集分析,以探索DEG的生物学作用。此外,应用“randomForest”软件包选择核心基因,用于创建神经网络模型。最后,在训练队列中,我们使用CIBERSORT评估CD组和正常组之间的免疫格局。富集分析结果表明,这些DEG可能参与了与免疫和炎症反应相关的生物学过程。此外,蛋白质-蛋白质相互作用网络中排名前三的枢纽基因是IL-1β、CCL2和CXCR2。该诊断模型具有显著的区分能力,ROC曲线下面积为0.984[95%置信区间:0.971-0.993]。利用一个验证队列(GSE36807)来确保模型的可靠性和适用性。此外,免疫浸润分析表明,CD组和健康对照组之间有9种不同的免疫细胞类型存在显著差异。总之,本研究为CD的诊断提供了新的见解,并为CD的精准治疗提供了潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e36/9520627/5a8501bac5c7/fgene-13-976578-g001.jpg

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