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基于机器学习的骨质疏松症和 2 型糖尿病共享枢纽基因与生物学机制的探索。

Exploration of the Shared Hub Genes and Biological Mechanism in Osteoporosis and Type 2 Diabetes Mellitus based on Machine Learning.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing, 400016, People's Republic of China.

Orthopedic Laboratory of Chongqing Medical University, Yuzhong, Chongqing, 400016, People's Republic of China.

出版信息

Biochem Genet. 2023 Dec;61(6):2531-2547. doi: 10.1007/s10528-023-10390-0. Epub 2023 May 4.

DOI:10.1007/s10528-023-10390-0
PMID:37140844
Abstract

A substantial amount of evidence suggests a close relationship between osteoporosis (OP) and Type 2 Diabetes Mellitus (T2DM), but the mechanisms involved remain unknown. Therefore, we conducted this study with the aim of screening for hub genes common to both diseases and conducting a preliminary exploration of common regulatory mechanisms. In the present study, we first screened genes significantly associated with OP and T2DM by the univariate logistic regression algorithm. And then, based on cross-analysis and random forest algorithm, we obtained three hub genes (ACAA2, GATAD2A, and VPS35) and validated the critical roles and predictive performance of the three genes in both diseases by differential expression analysis, receiver operating characteristic (ROC) curves, and genome wide association study (GWAS) analysis. Finally, based on gene set enrichment analysis (GSEA) and the construction of the miRNA-mRNA regulatory network, we conducted a preliminary exploration of the co-regulatory mechanisms of three hub genes in two diseases. In conclusion, this study provides promising biomarkers for predicting and treating both diseases and offers novel directions for exploring the common regulatory mechanisms of both diseases.

摘要

大量证据表明骨质疏松症(OP)和 2 型糖尿病(T2DM)之间存在密切关系,但涉及的机制尚不清楚。因此,我们进行了这项研究,旨在筛选两种疾病共有的枢纽基因,并对共同的调控机制进行初步探索。在本研究中,我们首先通过单变量逻辑回归算法筛选出与 OP 和 T2DM 显著相关的基因。然后,基于交叉分析和随机森林算法,我们获得了三个枢纽基因(ACAA2、GATAD2A 和 VPS35),并通过差异表达分析、接收器操作特征(ROC)曲线和全基因组关联研究(GWAS)分析验证了这三个基因在两种疾病中的关键作用和预测性能。最后,基于基因集富集分析(GSEA)和 miRNA-mRNA 调控网络的构建,我们对三种枢纽基因在两种疾病中的共同调控机制进行了初步探索。总之,本研究为预测和治疗两种疾病提供了有前途的生物标志物,并为探索两种疾病的共同调控机制提供了新的方向。

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本文引用的文献

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Butyrate oxidation attenuates the butyrate-induced improvement of insulin sensitivity in myotubes.丁酸盐氧化减弱了丁酸盐诱导的肌管胰岛素敏感性的改善。
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Ten SNPs May Affect Type 2 Diabetes Risk in Interaction with Prenatal Exposure to Chinese Famine.10 个单核苷酸多态性可能与中国饥荒时期的产前暴露相互作用影响 2 型糖尿病风险。
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Prevalent vertebral fracture is dominantly associated with spinal microstructural deterioration rather than bone mineral density in patients with type 2 diabetes mellitus.在 2 型糖尿病患者中,普遍存在的椎体骨折主要与脊柱微结构恶化有关,而不是与骨密度有关。
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Treatment of Osteoporosis.骨质疏松症的治疗
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YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism.YAP1 通过 TEADs 依赖性机制对于破骨细胞生成是必需的。
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