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主管单位 工业和信息化部 主办单位 哈尔滨工业大学 主编 任南琪 国际刊号ISSN 1672-5565 国内刊号CN 23-1513/Q

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引用本文:陈浩然,徐和福,陈熙勐,张皓旻,张钧栋,智鹏,李卓阳,刘格良,王毅兴,卢学春.氯雷他定的生物信息学分析及其对COVID-19的潜在治疗意义[J].生物信息学,2021,19(2):92-104.
CHEN Haoran,XU Hefu,CHEN Ximeng,ZHANG Haomin,ZHANG Jundong,ZHI Peng,LI Zhuoyang,LIU Geliang,WANG Yixing,LU Xuechun.Bioinformatics analysis of loratadine and its potential therapeutic significance for COVID-19[J].Chinese Journal of Bioinformatics,2021,19(2):92-104.
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氯雷他定的生物信息学分析及其对COVID-19的潜在治疗意义
陈浩然1,徐和福2,陈熙勐3,张皓旻3,张钧栋3,智鹏1,李卓阳1,刘格良1,王毅兴4,卢学春1
(1.山西医科大学 管理学院,太原 030000;2. 天津康复疗养中心 检验病理科,天津 300381;3. 解放军总医院 第二医学中心血液科 国家老年疾病临床医学研究中心,北京 100853;4. 同济大学附属东方医院 中医科,上海 200120)
摘要:
为探讨氯雷他定对新型冠状病毒肺炎的潜在治疗作用。从基因表达谱数据库(Gene expression omnibus,GEO)获取氯雷他定数据,分别进行差异分析、基因本体学(GO)富集分析、京都基因与基因组百科全书(KEGG)富集分析、蛋白质相互作用(Protein-protein interaction,PPI)网络分析并筛选关键基因,使用本课题组前期建立的表观精准治疗预测平台(Epigenomic Precision Medicine Prediction Platform,EpiMed)进行关联分析,筛选出负相关疾病、正相关药物及体内作用靶点,并在中、英文数据库中检索冠状病毒与关键基因作用的相关文献加以验证。共筛选出差异基因642个,其中上调230个,下调412个。其中,GO富集的基因大多参与炎症反应、激素作用和糖脂代谢等过程,KEGG通路富集主要和多种病毒感染、炎症介质、补体和凝血、消化道损伤、心律失常和氧化应激等过程或功能相关。结合EpiMed的预测结果,发现氯雷他定对全基因组表达谱的影响复杂,在PPI中,共得到642个蛋白,筛选出10个关键基因(Hub gene),主要与神经信号传导、磷酸化和炎症反应等功能相关,在EpiMed的结果中,预测出氯雷他定可能具有潜在治疗作用的疾病,包括严重急性呼吸综合征(SARS)、流行性感冒、社区获得性肺炎、严重脓毒症、呼吸道合胞病毒感染等,预测出对COVID-19可能具有治疗作用的药物,包括泛昔洛韦、奈韦拉平、氟伐他汀、磷酸氯喹、TNF-α抑制剂、金银花、虎杖、柴胡和知母等。通过文本挖掘,共检索到14篇冠状病毒与关键靶点作用相关的文献,验证了关键靶点的有效性。得出如下结论:氯雷他定对心脏调节,免疫反应,氧化应激和病毒感染等过程或通路具有调控作用,其可能在抗病毒的同时,还具有免疫调节和器官保护功能,对COVID-19危重症患者有潜在的治疗意义。
关键词:  氯雷他定  冠状病毒  基因表达谱  临床生物信息学  EpiMed
DOI:10.12113/202005005
分类号:Q93
文献标识码:A
基金项目:2017 年度国家老年疾病临床医学研究中心招标课题(No.NCRCG-PLAGH-2017011) ; 解放军总医院转化医学项目(No.2017TM-020).
Bioinformatics analysis of loratadine and its potential therapeutic significance for COVID-19
CHEN Haoran1, XU Hefu2, CHEN Ximeng3, ZHANG Haomin3, ZHANG Jundong3, ZHI Peng1, LI Zhuoyang1, LIU Geliang1, WANG Yixing4,LU Xuechun1
(1. School of Management, Shanxi Medical University, Taiyuan 030000,China; 2. Department of Laboratory Pathology, Tianjin Rehabilitation and Sanatorium Center, Tianjin 300381, China; 3. Department of Hematology, Second Medical Center, PLA General Hospital, Beijing 100853, China; 4. Department of Traditional Chinese Medicine, Oriental Hospital of Tongji University, Shanghai 200120, China)
Abstract:
To explore the potential therapeutic effect of loratadine on new coronavirus pneumonia (COVID-19), loratadine data was obtained from Gene Expression Omnibus (GEO). Differential analysis, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Protein-Protein Interaction (PPI) network analysis were conducted,and key genes were screened. Using the Epigenomic Precision Medicine Prediction Platform (EpiMed) established earlier by the research group for correlation analysis, the negatively related diseases, positive relevant drugs, and targets in vivo were screened out, and the literature of coronavirus and key targets in Chinese and English databases were studied for verification. Results show that a total of 642 differential genes were screened out, including 230 up-regulated and 412 down-regulated. Among them, most of the genes enriched in GO were involved in the processes of inflammatory reaction, hormone action, and metabolism of glycolipids. The KEGG pathway was mainly enriched with various viral infections, inflammatory mediators, complement and coagulation, digestive tract damage, arrhythmia, and oxidative stress. Combined with the prediction results of EpiMed, it was found that the effect of loratadine on the genome-wide expression profile was complex. In PPI, a total of 642 proteins were obtained, and 10 hub genes were selected, mainly related to nerve signal transduction, phosphorylation, inflammatory response, and other functions. EpiMed results indicate that loratadine may have potential therapeutic effects, including severe acute respiratory syndrome (SARS), influenza, community-acquired pneumonia, severe sepsis, respiratory syncytial virus infection, etc. Drugs that may have a therapeutic effect on COVID-19 were predicted, including etanercept, famciclovir, nevirapine, fluvastatin, chloroquine phosphate, polygonum cuspidatum, houttuynia cordata, forsythia, liquorice, and common anemarrhena rhizome. Through text mining, a total of 14 articles related to the role of coronaviruses and key targets were retrieved, which verified the effectiveness of the key targets. Therefore, loratadine can regulate heart regulation, immune response, oxidative stress, viral infections, and other processes or pathways. It may have anti-viral, immune regulation, and organ protection functions at the same time. The results have potential therapeutic significance for COVID-19 critically ill patients.
Key words:  Loratadine  Coronavirus  Gene expression profile  Clinical bioinformatics  EpiMed

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