重组炭疽疫苗免疫人体产生抗体基因的生物信息学分析  

Bioinformatics Analysis for Variable Domain Sequence of Human Immunoglobulin Elicited by Recombinant Anthrax Vaccine

作　　者：刘渝娇 陈郑珊 王美荣 张冠英 范鹏飞 房婷 迟象阳 于长明 LIU Yu-Jiao;CHEN Zheng-Shan;WANG Mei-Rong;ZHANG Guan-Ying;FAN Peng-Fei;FANG Ting;CHI Xiang-Yang;YU Chang-Ming(Beijing Institute of Biotechnology,Beijing 100071,China)

机构地区：[1]军事科学院军事医学研究院生物工程研究所,北京100071

出　　处：《生物技术通讯》2018年第2期174-182,共9页Letters in Biotechnology

基　　金：国家科技重大专项课题重大新药创制(2018ZX09J18101)

摘　　要：目的:采用多种生物信息学手段,提取并分析前期获得的重组炭疽疫苗免疫人体产生的抗体基因序列的特征信息,探究与抗体进化规律和功能预测相关的线索。方法:利用R、Perl等语言编写了一系列数据处理和接口程序,整合集成Change-O等相关程序集和R语言包构建抗体基因序列分析平台,对抗体重链基因的VDJ基因使用频率、聚类分布、CDR3区理化特性及体细胞高频突变模式进行信息提取,并通过在线服务器得到部分数据可视化结果。结果:前期获得的抗体基因序列中IGHV3、IGHD3和IGHJ4的使用频率最高,而IGHV3和IGHD5、IGHD6和IGHJ4、IGHV3和IGHJ4的组合是序列中出现频率最高的组合方式;23.3%的保护性抗原(PA)结合抗体都出现在同一个抗体聚类(239号克隆组)中;中和抗体HCDR3区较其他抗体对于碱性和酸性氨基酸使用频率较低,偏向于使用疏水性氨基酸;抗体的体细胞高频突变多发生在AAAAC、GTTAA、AGCTC、AAGTA等热点motif。结论:相关生物信息学手段能够有效处理和分析大量的抗体基因序列,研究结果和方法可为重组疫苗评价以及抗体鉴定和改造提供信息和方法学帮助。Objective:Using bioinformatics methods to extract and analyze the characteristic of a large number of variable domain sequences of immunoglobulin elicited by recombinant anthrax protective antigen(PA)vaccine obtained previously,and exploring clues related to immunoglobulin evolution and function prediction.Methods:Utilizing a series of data processing programs and application interface written by R language and a set of modules such as Change-O to build the immunoglobulin variable domain analysis platform to count the VDJ genes using frequency,clustering distribution,physical and chemical properties of CDR3 regions and somatic hypermutation hot/cold-spot motifs for information extraction.Results:The using frequency of IGHV3,IGHD3 and IGHJ4 was highest among the previously obtained immunoglobulin variable domain sequences.The combination of IGHV3 and IGHD5,IGHD6 and IGHJ4,IGHV3 and IGHJ4 were the most frequent combination in the sequences.There were 23.3%of the PA-binding antibodies appearing in one clonally related cluster(group 239).The CDR3 region of neutralizing antibodies showed less usage of basic and acidic amino acids than other antibodies,inclining to use hydrophobic amino acids.The somatic hypermutation hot/cold-spot motifs of antibodies occurred mostly in hotspots such as AAAAC,GTTAA,AGCTC and AAGTA.Conclusion:Related bioinformatics methods can effectively process and analyze a large number of immunoglobulin variable domain sequences.The research results and methods can provide information and methodological assistance for the evaluation of recombinant PA vaccines and antibody identification and modification

关 键 词：抗体基因 序列分析 生物信息学 炭疽疫苗 

分 类 号：Q811.4[生物学—生物工程] R392.1[医药卫生—免疫学]