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生物信息学分析和机器学习方法在鉴定非酒精性脂肪性肝病新关键基因中的应用。

Bioinformatics analysis and machine learning approach applied to the identification of novel key genes involved in non-alcoholic fatty liver disease.

机构信息

Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Sci Rep. 2023 Nov 22;13(1):20489. doi: 10.1038/s41598-023-46711-x.

Abstract

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver.

摘要

非酒精性脂肪性肝病(NAFLD)是由肝脏中甘油三酯积累引起的一系列慢性肝病,在早期阶段,被归类为非酒精性脂肪性肝病(NAFLD)或单纯性脂肪肝的肝脂肪变性。非酒精性脂肪性肝炎(NASH)的死亡率高于 NAFLD;因此,早期诊断该病可能会减少肝损伤并提高生存率。在本研究中,我们从公共数据集 GEO 筛选了 NAFLD 患者和对照样本的基因表达数据,以检测差异表达基因(DEGs)。然后,评估了 top 选择的 DEGs 与临床数据之间的相关性。在本研究中,我们下载了两个 GEO 数据集(GSE48452、GSE126848)。通过机器学习方法(惩罚回归模型)识别失调表达基因(DEGs)。然后,使用验证数据集验证两个训练数据集之间的共享 DEGs。ROC 曲线分析用于识别诊断标志物。R 软件分析了 DEGs、临床数据和脂肪肝之间的相互作用。在 NAFLD 和健康个体之间发现了 10 个新的差异表达基因,包括 ABCF1、SART3、APC5、NONO、KAT7、ZPR1、RABGAP1、SLC7A8、SPAG9 和 KAT6A。基于验证结果和 ROC 分析,鉴定 NR4A2 和 IGFBP1b 为诊断标志物。这些关键基因可能是脂肪肝发展的预测标志物。建议进一步评估这些关键基因作为脂肪肝发展过程中的可能预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da80/10665370/be414138191e/41598_2023_46711_Fig1_HTML.jpg

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