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基于加权基因共表达网络分析和LASSO算法的克罗恩病潜在功能模块和诊断基因的鉴定

Identification of Potential Functional Modules and Diagnostic Genes for Crohn's Disease Based on Weighted Gene Co-expression Network Analysis and LASSO Algorithm.

作者信息

Wang Ruiquan, Zhao Hongqi

机构信息

Department of Pathology, Jinhua People's Hospital, Jinhua, Zhejiang, China.

Department of Pathology, Jinhua Guangfu Hospital, Jinhua, Zhejiang, China.

出版信息

Turk J Gastroenterol. 2025 Jan 6;36(4):209-218. doi: 10.5152/tjg.2025.23605.

DOI:10.5152/tjg.2025.23605
PMID:40181741
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12001489/
Abstract

BACKGROUND/AIMS: Accurate diagnosis of Crohn's disease (CD) is paramount due to its resemblance to other inflammatory bowel diseases. Early and precise diagnosis plays a pivotal role in tailoring personalized treatments, thereby enhancing the quality of life for CD patients.

MATERIALS AND METHODS

Differential gene expression analysis was conducted to identify genes from the mRNA expression profiles of CD samples, followed by pathway enrichment analysis. The immune cell infiltration levels of each CD patient sample were assessed. Using weighted gene co-expression network analysis, key gene modules linked to CD were found. Hub gene identification was made easier by the construction of protein-protein interaction networks. Next, utilizing the Least Absolute Shrinkage and Selection Operator on the hub genes in the training set, a diagnostic model was created. The accuracy of the model was then confirmed using a different validation set.

RESULTS

Our analysis revealed 651 differentially expressed genes, enriched in leukocyte chemotaxis and inflammation-related pathways. Immunization results showed a higher abundance of T cells CD4 memory resting, macrophages M2, and plasma cells in CD patients. Weighted gene co-expression network analysis linked the turquoise module with macrophages M2. Eight hub genes (APOA1, APOA4, CYP2C8, CYP2C9, CYP2J2, EPHX2, HSD3B1, and LPL) formed the diagnostic model, exhibiting excellent diagnostic performance with area under curve values of 0.94 (training set) and 0.941 (validation set).

CONCLUSION

The CD diagnostic model, based on hub genes, shows exceptional diagnostic accuracy, providing a valuable reference for CD diagnosis.

摘要

背景/目的:由于克罗恩病(CD)与其他炎症性肠病相似,其准确诊断至关重要。早期精确诊断在制定个性化治疗方案中起着关键作用,从而提高CD患者的生活质量。

材料与方法

进行差异基因表达分析,以从CD样本的mRNA表达谱中识别基因,随后进行通路富集分析。评估每个CD患者样本的免疫细胞浸润水平。使用加权基因共表达网络分析,发现与CD相关的关键基因模块。通过构建蛋白质-蛋白质相互作用网络,更便于鉴定枢纽基因。接下来,对训练集中的枢纽基因应用最小绝对收缩和选择算子,创建诊断模型。然后使用不同的验证集确认模型的准确性。

结果

我们的分析揭示了651个差异表达基因,这些基因富集于白细胞趋化和炎症相关通路。免疫分析结果显示,CD患者中静止的CD4记忆T细胞、M2巨噬细胞和浆细胞的丰度更高。加权基因共表达网络分析将蓝绿色模块与M2巨噬细胞联系起来。八个枢纽基因(载脂蛋白A1、载脂蛋白A4、细胞色素P450 2C8、细胞色素P450 2C9、细胞色素P450 2J2、环氧化物水解酶2、3β-羟基类固醇脱氢酶1和脂蛋白脂肪酶)构成了诊断模型,其曲线下面积值在训练集为0.94,在验证集为0.941,表现出优异的诊断性能。

结论

基于枢纽基因的CD诊断模型显示出卓越的诊断准确性,为CD诊断提供了有价值的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/fa8131c7f7de/tjg-36-4-209_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/fa8131c7f7de/tjg-36-4-209_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/6a4dabd4b18a/tjg-36-4-209_f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/bcbfcb90979e/tjg-36-4-209_f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/e7c93fef9b85/tjg-36-4-209_f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/466ac4febefb/tjg-36-4-209_f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/fa8131c7f7de/tjg-36-4-209_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/fa8131c7f7de/tjg-36-4-209_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/6a4dabd4b18a/tjg-36-4-209_f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/bcbfcb90979e/tjg-36-4-209_f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/e7c93fef9b85/tjg-36-4-209_f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/466ac4febefb/tjg-36-4-209_f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65f/12001489/fa8131c7f7de/tjg-36-4-209_f001.jpg

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本文引用的文献

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