通过时间基因表达谱分析探究异烟肼引起肝损伤的机制

doi:10.16288/j.yczz.22-069

遗传 ›› 2022, Vol. 44 ›› Issue (6): 501-509.doi: 10.16288/j.yczz.22-069

通过时间基因表达谱分析探究异烟肼引起肝损伤的机制

田子钊(), 周晨希, 周伟, 李沫, 褚云鹏, 怀聪(), 秦胜营()

上海交通大学Bio-X研究院,上海 200030

收稿日期:2022-03-10 修回日期:2022-04-26 出版日期:2022-06-20 发布日期:2022-05-11
通讯作者: 怀聪,秦胜营 E-mail:tianzizhao@sjtu.edu.cn;huaic@sjtu.edu.cn;chinsir@sjtu.edu.cn
作者简介:田子钊,在读硕士研究生,专业方向：生物学。E-mail: tianzizhao@sjtu.edu.cn
基金资助:
国家自然科学基金项目资助编号(81773818);国家自然科学基金项目资助编号(82003856)

Analysis of time-series gene expression data to explore mechanisms of isoniazid-induced liver toxicity

Zizhao Tian(), Chenxi Zhou, Wei Zhou, Mo Li, Yunpeng Chu, Cong Huai(), Shengying Qin()

Bio-X Institute, Shanghai Jiaotong University, Shanghai 200030, China

Received:2022-03-10 Revised:2022-04-26 Online:2022-06-20 Published:2022-05-11
Contact: Huai Cong,Qin Shengying E-mail:tianzizhao@sjtu.edu.cn;huaic@sjtu.edu.cn;chinsir@sjtu.edu.cn
Supported by:
Supported by the National Nature Science Foundation of China Nos(81773818);Supported by the National Nature Science Foundation of China Nos(82003856)

摘要/Abstract

摘要：

抗结核药物异烟肼具有肝脏毒性,其发生机制需要进一步阐明。本研究使用异烟肼处理肝细胞,分析不同处理时间表达谱的差异。通过对差异表达基因进行聚类分析和功能富集分析,共得到6个与肝脏毒性相关的基因簇和一系列相关通路;进一步通过蛋白互作分析和时间序列差异分析方法,筛选出表达水平具有时间依赖性的13个关键基因。本研究结果为理解异烟肼引发肝脏毒性过程提供了思路,为今后药物性肝脏毒性的监测以及治疗提供了新的靶基因。

关键词: 异烟肼, 肝细胞, 肝脏毒性, 时间序列分析

Abstract:

Isoniazid (INH) is a first-line anti-tuberculosis drug which can cause idiosyncratic liver injury, while the underlying mechanisms need to be further elucidated. In this study, we explored the time series gene expression profiling of a hepatocyte cell line under isoniazid treatment. Through cluster analysis and enrichment analysis of differentially expressed genes, we revealed a total of 6 gene clusters and a series of pathways related to hepatotoxicity, and 13 key candidate genes were identified according to the protein-protein interaction (PPI) network analysis and maSigPro analysis. These findings lay a foundation for understanding the mechanisms of isoniazid -induced liver toxicity and provide new target genes for the monitoring and treatment of INH-induced hepatotoxicity in the future.

Key words: isoniazid, hepatocytes, liver toxicity, time series analysis

田子钊, 周晨希, 周伟, 李沫, 褚云鹏, 怀聪, 秦胜营. 通过时间基因表达谱分析探究异烟肼引起肝损伤的机制[J]. 遗传, 2022, 44(6): 501-509.

Zizhao Tian, Chenxi Zhou, Wei Zhou, Mo Li, Yunpeng Chu, Cong Huai, Shengying Qin. Analysis of time-series gene expression data to explore mechanisms of isoniazid-induced liver toxicity[J]. Hereditas(Beijing), 2022, 44(6): 501-509.

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样本名称	质控数据	Q30 (%)	GC (%)	比对率(%)	样本名称	质控数据	Q30 (%)	GC (%)	比对率(%)
6h-1	32847297	95.14	53.39	96.27	18h-1	26368961	94.78	53.41	95.71
6h-2	34042755	95.16	53.32	96.08	18h-2	29140435	94.5	53.4	95.52
6h-3	34027030	94.68	53.61	96.30	18h-3	33440673	95.32	53.24	95.65
12h-1	30967636	94.71	53.46	95.77	24h-1	30981366	95.59	53.61	96.28
12h-2	30948041	94.73	53.34	96.02	24h-2	29293294	94.83	53.81	93.50

组合	12h vs 6h	18h vs 12h	24h vs 18h
上调基因数目	415	195	643
下调基因数目	180	84	928
合计	595	279	1571

基因名称	所属 Cluster
KAT6A、ARID1A、BCOR	Cluster1
TP53BP1、BUB1B	Cluster3
SRCAP	Cluster4
MRPL27、MRPL39、MALSU1、MRPL17、MRPL36、MRPS18B、MRPL46	Cluster6

通过时间基因表达谱分析探究异烟肼引起肝损伤的机制

Analysis of time-series gene expression data to explore mechanisms of isoniazid-induced liver toxicity

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