Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai 200127, China.
Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Aging (Albany NY). 2020 Oct 24;12(20):20471-20482. doi: 10.18632/aging.103861.
Ulcerative colitis is a type of inflammatory bowel disease characterized by chronic and recurrent nonspecific inflammation of the intestinal tract. To find susceptibility genes and develop a novel predictive model of ulcerative colitis, two sets of cases and a control group containing the ulcerative colitis gene expression profile (training set GSE109142 and validation set GSE92415) were downloaded and used to identify differentially expressed genes. A total of 781 upregulated and 127 downregulated differentially expressed genes were identified in GSE109142. The random forest algorithm was introduced to determine 1 downregulated and 29 upregulated differentially expressed genes contributing highest to ulcerative colitis occurrence. Expression data of these 30 genes were transformed into gene expression scores, and an artificial neural network model was developed to calculate differentially expressed genes weights to ulcerative colitis. We established a universal molecular prognostic score (mPS) based on the expression data of the 30 genes and verified the mPS system with GSE92415. Prediction results agreed with that of an independent data set (ROC-AUC=0.9506/PR-AUC=0.9747). Our research creates a reliable predictive model for the diagnosis of ulcerative colitis, and provides an alternative marker panel for further research in disease early screening.
溃疡性结肠炎是一种炎症性肠病，其特征为肠道的慢性和复发性非特异性炎症。为了寻找易感性基因并开发溃疡性结肠炎的新型预测模型，我们下载了两组病例和一个对照基因表达谱数据集（训练集 GSE109142 和验证集 GSE92415），用于识别差异表达基因。在 GSE109142 中鉴定出 781 个上调和 127 个下调的差异表达基因。我们引入随机森林算法确定了 1 个下调和 29 个上调的差异表达基因，这些基因对溃疡性结肠炎的发生贡献最大。这些 30 个基因的表达数据被转化为基因表达评分，并建立了人工神经网络模型来计算差异表达基因对溃疡性结肠炎的权重。我们基于这 30 个基因的表达数据建立了一个通用的分子预后评分（mPS）系统，并使用 GSE92415 对 mPS 系统进行了验证。预测结果与独立数据集一致（ROC-AUC=0.9506/PR-AUC=0.9747）。我们的研究为溃疡性结肠炎的诊断建立了一个可靠的预测模型，并为疾病早期筛查的进一步研究提供了替代标志物面板。
