|本期目录/Table of Contents|

[1]周红,吴梅,李鑫.利用加权基因共表达网络分析识别胆道闭锁相关的枢纽基因[J].天津医科大学学报,2022,28(02):123-128.
　ZHOU Hong,WU Mei,LI Xin.Identification of hub genes in biliary atresia by weighted gene co-expression network analysis[J].Journal of Tianjin Medical University,2022,28(02):123-128.
点击复制

利用加权基因共表达网络分析识别胆道闭锁相关的枢纽基因(PDF)
分享到：

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
28卷
期数:
2022年02期
页码:
123-128
栏目:
生物信息学专题
出版日期:
2022-03-20

文章信息/Info

Title:
Identification of hub genes in biliary atresia by weighted gene co-expression network analysis
文章编号:
1006-8147(2022)02-0123-06
作者:
周红1; 吴梅1; 李鑫2
（1.宜宾市第一人民医院儿科，宜宾 644000; 2. 乌鲁木齐儿童医院普外科，乌鲁木齐 830000）
Author(s):
ZHOU Hong1; WU Mei1; LI Xin2
（1.Department of Paediatrics，Yibin First People's Hospital，Yibin 644000，China；2.Department of General Surgery，Urumqi Children′s Hospital，Urumqi 830000，China）
关键词:
胆道闭锁; 加权共表达网络分析; 枢纽基因
Keywords:
biliary atresia; WGCNA; hub gene
分类号:
R722.1
DOI:
-
文献标志码:
A
摘要:
目的：通过加权基因共表达网络分析（WGCNA）识别胆道闭锁（BA）发病相关的枢纽基因。方法：从基因表达汇编（GEO）数据库下载BA基因芯片数据集GSE46960，利用WGCNA构建基因共表达网络，识别与BA相关的模块与枢纽基因，对关键模块进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。结果：通过WGCNA分析构建了20个基因共表达模块，确定与BA显著相关的模块为黄色模块（r=0.69，P＜0.05），将黄色模块中的基因按基因连通性及基因显著性的不同阈值进一步筛选出16个枢纽基因。对黄色模块进行GO及KEGG分析显示，与BA显著相关的基因主要富集在细胞外基质（ECM）、细胞黏附分子、色氨酸代谢、甘油磷脂代谢、过氧化物酶体增殖物激活受体（PPAR）信号通路。结论：利用WGCNA方法识别出与BA相关的关键模块和16个枢纽基因，其中新发现有12个基因可能与BA发病相关，可能帮助阐明BA发病的机制。
Abstract:
Objective：To identify hub genes related to the pathogenesis of biliary atresia（BA） by weighted gene co-expression network analysis（WGCNA）. Methods：The BA gene chip dataset GSE46960 was downloaded from the Gene Expression Omnibus （GEO） database，and the gene co-expression network was constructed by WGCNA. The modules and hub genes related to biliary atresia were screened out，and the key module were analyzed by Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）. Results：Twenty gene co-expression modules were constructed through WGCNA，and the module related to biliary atresia were identified as yellow modules（r=0.69，P＜0.05）. The genes in the yellow module were further screened for 16 hub genes according to different thresholds of gene connectivity and gene significance. The results of GO and KEGG analysis on yellow module genes showed that genes significantly associated with biliary atresia were mainly enriched in extracellular matrix，cell adhesion molecules，tryptophan metabolism，glycerophospholipid metabolism and PPAR signaling pathway. Conclusion：WGCNA method is used to identify the key modules and 16 hub genes related to biliary atresia，of which 12 genes may be related to the pathogenesis of biliary atresia，which may help to clarify the pathogenesis of biliary atresia.

参考文献/References:

[1] HARTLEY J L，DAVENPORT M，KELLY D A. Biliary atresia[J]. Lancet，2009，374（9702）：1704-1713.
[2] 蔡威，孙宁，魏光辉. 小儿外科学[M]. 第5版. 北京： 人民卫生出版社，2014：370-375.
[3] KAZUHIKO B，REENA M，PRANAVKUMAR S，et al. Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease[J]. Hepatology，2014，60（1）： 211-223.
[4] LIU J，ZHANG C，WU H，et al. Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression[J]. J Clin Invest，2020，130（6）：3253-3269.
[5] SERINET M O，WILDHABER B E，BROU?魪 P，et al. Impact of age at Kasai operation on its results in late childhood and adolescence：a rational basis for biliary atresia screening[J]. Pediatrics，2009，123（5）：
1280-1286.
[6] BEDNAREK J，TRAXINGER B，BRIGHAM D，et al. Cytokine-producing B cells promote immune-mediated bile duct injury in murine biliary atresia[J]. Hepatology，2018，68（5）：1890-1904.
[7] KLEMANN C，SCHR?魻DER A，DREIER A，et al. Interleukin 17，produced by γδ T cells，contributes to hepatic inflammation in a mouse model of biliary atresia and is increased in livers of patients[J]. Gastroenterology，2016，150（1）：229-241.
[8] LANE E，MURRAY K F. Neonatal cholestasis[J]. Pediatr Clin North Am，2017，64（3）：621-639.
[9] PROM-ON S，CHANTHAPHAN A，CHAN J，et al. Enhancing biological relevance of a weighted gene co-expression network for functional module identification[J]. J Bioinform Comput Biol，2011， 9（1）：111-129.
[10] LIU Q，JIANG C，XU J，et al. Genome-wide temporal profiling of transcriptome and open chromatin of early cardiomyocyte differentiation derived from hiPSCs and hESCs[J]. Circ Res，2017，121（4）：376-391.
[11] BETTENCOURT C，FOTI S，MIKI Y，et al. White matter DNA methylation profiling reveals deregulation of HIP1，LMAN2，MOBP，and other loci in multiple system atrophy[J]. Acta Neuropathol，2020， 139（1）：135-156.
[12] YIN K，ZHANG Y，ZHANG S，et al. Using weighted gene co-expression network analysis to identify key modules and hub genes in tongue squamous cell carcinoma[J]. Medicine，2019，98（37）：e17100.
[13] BONNANS C，CHOU J，WERB Z. Remodelling the extracellular matrix in development and disease[J]. Nat Rev Mol Cell Biol，2014，15（12）：786-801.
[14] NéMETH ?魣，M?魷ZES M M，CALVIER L，et al. The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3[J]. BMC Nephrol，2019，20（1）：245.
[15] HUANG C，CHUANG J，CHOU M，et al. Matrilysin（MMP-7） is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis[J]. Mod Pathol，2005，18（7）：941-950.
[16] LERTUDOMPHONWANIT C，MOURYA R，FEI L，et al. Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia[J]. Sci Transl Med，2017，9（417）.
[17] JIANG J，WANG J，SHEN Z，et al. Serum MMP-7 in the diagnosis of biliary atresia[J]. Pediatrics，2019，144（5）:e20190902.
[18] YANG L，ZHOU Y，XU P，et al. Diagnostic accuracy of serum matrix metalloproteinase-7 for biliary atresia[J]. Hepatology，2018，68（6）：2069-2077.
[19] HERTEL P M，CRAWFORD S E，FINEGOLD M J，et al. Osteopontin upregulation in rotavirus-induced murine biliary atresia requires replicating virus but is not necessary for development of biliary atresia[J]. Virology，2011，417（2）：281-292.
[20] BRINDLEY S，LANHAM A，KARRER F，et al. Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells[J]. Hepatology，2012， 55（4）：1130-1138.
[21] KURIAN S，WILLIAMS A，GELBART T，et al. Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling[J]. Am J Transplant，2014，14（5）：1164-1172.

相似文献/References:

[1]卫园园 综述,詹江华 审校.胆道闭锁流行病学研究进展[J].天津医科大学学报,2017,23(05):480.
[2]陈 扬,余 晨,熊希倩,等.同卵双胞胎胆道闭锁患儿染色体核型和全外显子组测序分析[J].天津医科大学学报,2019,25(04):391.
　CHEN Yang,YU Chen,XIONG Xi-qian,et al.The study of chromosome and whole exome sequencing of monozygotic twins with biliary atresia[J].Journal of Tianjin Medical University,2019,25(02):391.
[3]杨芳 综述,詹江华 审校.胆道闭锁肝门肠吻合术式研究进展[J].天津医科大学学报,2020,26(06):587.
[4]阿里木江·阿不都热依木,李鑫,王皓杰.术前营养状况对胆道闭锁Kasai术后自体肝生存的影响[J].天津医科大学学报,2021,27(03):266.
　Alimujiang·Abudureyimu,LI Xin,WANG Hao-jie.The influence of preoperative nutritional status on native liver survival after Kasai for biliary atresia[J].Journal of Tianjin Medical University,2021,27(02):266.
[5]张瑞丰,李腾飞,刘邵文,等.血ALP、GGT、TBA在胆道闭锁中的诊断价值及临床意义[J].天津医科大学学报,2022,28(05):472.
　ZHANG Rui-feng,LI Teng-fei,LIU Shao-wen,et al.Diagnostic value and clinical significance of blood ALP，GGT and TBA in biliary atresia[J].Journal of Tianjin Medical University,2022,28(02):472.
[6]刘志杰,林峰,王皓洁,等.免疫炎症指数与胆道闭锁Kasai术后自体肝生存时间相关：倾向性评分匹配分析[J].天津医科大学学报,2023,29(03):295.
　LIU Zhi-jie,LIN Feng,WANG Hao-jie,et al.Correlation of immune-inflammation index with native liver survival after Kasai surgery for biliary atresia：propensity score matching analysis[J].Journal of Tianjin Medical University,2023,29(02):295.
[7]刘志杰综述,詹江华审校.肝巨噬细胞在胆道闭锁肝纤维化中的作用[J].天津医科大学学报,2023,29(04):453.

备注/Memo

备注/Memo:
基金项目 新疆维吾尔自治区自然科学基金（2019D01A12）
作者简介 周红（1990-），女，医师，学士，研究方向：儿科学，E-mail：734179691@qq.com。
更新日期/Last Update: 2022-03-20