Obesity,Metabolically unhealthy obesity,Metabolically healthy obesity,Bioinformatics analysis,Weighted gene co-expression network analysis
,"/> <span style="font-size:14px;line-height:2;">基于加权基因共表达网络分析研究代谢</span><span style="font-size:14px;line-height:2;">异常型肥胖儿童的全血转录组特征</span>
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发育医学电子杂志  2022, Vol. 10 Issue (3): 161-167    DOI: 10.3969/j.issn.2095-5340.2022.03.001
  生长发育   论著 |
基于加权基因共表达网络分析研究代谢异常型肥胖儿童的全血转录组特征
王青青 张锐锋 葛星
1. 徐州市儿童医院 肾内风湿免疫科,江苏 徐州 221006;2. 徐州医科大学 基础医学院,江苏 徐州 221004
Study of whole-blood transcriptome of children with metabolically unhealthy obesity based on weighted gene co-expression network analysis
Wang Qingqing, Zhang Ruifeng, Ge Xing
1.Department of Nephrology and Rheumatology, XuzhouChildren's Hospital, Jiangsu, Xuzhou 221006, China; 2.College of Basic Medicine, Xuzhou Medical University, Jiangsu, Xuzhou 221004, China
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摘要 【摘要】 目的  分析代谢异常型肥胖(metabolically unhealthy obesity,MUO)和代谢正常型肥胖
(metabolically healthy obesity,MHO)儿童的全血转录组特征,探讨MUO 的生物标志物。 方法 采
用Gene Expression Omnibus(GEO)数据库的GSE146869 数据集,包括27 例肥胖儿童的全血转录组测序数据,其中13 例MHO 儿童,14 例MUO 儿童。利用R 软件的“Limma”包,分析全血细胞中的差异表达基因。使用基因本体论(gene ontology,GO)富集分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析、蛋白互作(protein-protein interaction,PPI)网络分析等生物信息学方法,探索差异表达基因的生物学功能。使用加权基因共表达网络分析(weighted geneco-expression network analysis,WGCNA),将差异表达基因聚类为模块,探索MUO 的生物标志物或潜在治疗靶点。使用R 软件进行生物信息分析和统计学分析。 结果  MHO 组与MUO 组儿童的性别、年龄、体质量指数、收缩压、舒张压、空腹血糖、胰岛素含量和胰岛素抵抗指数比较,差异均无统计学意义(P 值均>0.05)。MUO 组血清三酰甘油、白细胞介素-6 和肿瘤坏死因子-α 含量高于MHO 组(P 值均<0.05)。与MHO 组相比,MUO 组上调109 个基因,下调77 个基因。186 个差异表达基因富集到46 个GO 条目和3 条KEGG 通路。其中,细胞分裂周期5 样蛋白(cell division cycle 5 like,CDC5L)、CTP 合酶1(CTP synthase 1,CTPS1)和主要组织相容性复合体Ⅰ C(major histocompatibility complexclass Ⅰ -C,HLA-C)基因为PPI 网络图的枢纽基因。WGCNA将186 个差异表达基因聚类生成5 个模块,在青色模块中,切割和聚腺苷酸化特异因子7(cleavage and polyadenylation specific factor 7,CPSF7)处于核心位置,为枢纽基因。 结论 186 个差异表达基因和5 个模块可以作为儿童MUO 的潜在靶标,其中CDC5L、CTPS1、HLA-C 和CPSF7 基因可能在MUO 发生、发展中扮演重要的角色。
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关键词:  肥胖  代谢异常型肥胖  代谢正常型肥胖  生物信息学分析  加权基因共表达网络分析    
Abstract: 【Abstract】 Objective To analyze the characteristics of the whole-blood transcriptome of children with
metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO), in order to find the
biomarkers of MUO. Method The GSE146869 data set of Gene Expression Omnibus (GEO) database
was used, including the whole-blood transcriptome sequencing data of 27 obese children (13 MHO children
and 14 MUO children). The Limma package of R software was used to analyze the differentially expressed
genes in the whole-blood cells. Bioinformatics methods such as gene ontology (GO) enrichment analysis,
Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analysis were used to explore the biological functions of differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) was used to cluster differentially expressed genes into modules, and to explore biomarkers or potential therapeutic targets for MUO. Bioinformatics analysis and statistical analysis were performed by R software. Result There was no significant difference in gender, age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin content and insulin resistance index between MHO group and MUO group (all P>0.05). Serum triglyceride, interleukin- 6 and tumor necrosis factor-α in MUO group was higher than that in MHO group (all P<0.05). Compared with the MHO group, 109 genes were up-regulated and 77 genes were down-regulated in the MUO group. The 186 differentially expressed genes were enriched into 46 GO entries and 3 KEGG pathways. Among the differentially expressed genes, cell division cycle 5 like (CDC5L), CTP synthase 1 (CTPS1) and major histocompatibility complex class Ⅰ-C (HLA-C) genes were the hub genes of PPI network map. In addition, WGCNA clustered 186 differentially expressed genes into 5 modules. In the cyan module, cleavage and polyadenylation specific factor 7 (CPSF7) was at the core and was the hub gene. Conclusion 186 differentially expressed genes and 5 modules can be used as potential targets for children with MUO, among which CDC5L, CTPS1, HLA-C and CPSF7 genes may play an essential role in the occurrence and development of MUO.
Key words:  Obesity')" href="#">Obesity    Metabolically unhealthy obesity    Metabolically healthy obesity    analysis')" href="#">Bioinformatics analysis    Weighted gene co-expression network analysis
收稿日期:  2021-07-13                     发布日期:  2022-05-30     
基金资助: 江苏省研究生科研与实践创新计划(KYCX20_2445)
通讯作者:  葛星    E-mail:  400002022001@xzhmu.edu.cn
引用本文:    
王青青 张锐锋 葛星. 基于加权基因共表达网络分析研究代谢异常型肥胖儿童的全血转录组特征[J]. 发育医学电子杂志, 2022, 10(3): 161-167.
Wang Qingqing, Zhang Ruifeng, Ge Xing. Study of whole-blood transcriptome of children with metabolically unhealthy obesity based on weighted gene co-expression network analysis. Journal of Developmental Medicine(Electronic Version), 2022, 10(3): 161-167.
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[2] 贾佳 施荣伟 郑凯 等. 南京市中学生超重肥胖现状及影响因素的研究[J]. 发育医学电子杂志, 2020, 8(2): 135-139.
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