基于VHSE结构表征的HLA-B＊5701和B＊5801配体亲和特性研究  

The VHSE-based classifications of the peptide ligands of HLA-B＊5701 and HLA-B＊5801

作　　者：王青[2] 梅虎[1,2] 张亚兰[2] 潘显超[2] 谭文[2] 晁丽[2] 

机构地区：[1]生物流变科学与技术教育部重点实验室,重庆大学,重庆400044 [2]重庆大学生物工程学院,重庆400044

出　　处：《计算机与应用化学》2013年第1期43-47,共5页Computers and Applied Chemistry

基　　金：国家自然科学基金资助项目(61073135);国家外专/教育部“111”创新引智计划资助

摘　　要：基于VHSE(Principal component score vector of hydrophobic,steric,and electronic properties)结构表征方法,采用支持向量机结合遗传算法变量筛选技术,分别建立B*5701和B*5801多肽亲和活性的分类预测模型,其最优线性模型内部验证的灵敏度(Sensitivity,Sen)、特异性(Specificity,Spe)、接受者操作特征曲线下面积(Area under receiver operating characteristics curve,AUC)和马休斯相关系数(Matthews coefficient of correlation,MCC)分别为77.29%、93.99%、93.02%、67.65%(B*5701)和78.08%、89.62%、88.34%、64.73%(B*5801);外部验证的Sen、Spe、AUC和MCC分别为80.02%、94.53%、94.62%、72.09%(B*5701)和77.43%、90.79%、87.98%、66.20%(B*5801)。依据最优模型,分别对B*5701和B*5801配体的亲和特性进行了细致的比较和分析,研究结果可为Abacavir的HLA-B*5701限制性药物毒副作用(Serious Adverse Drug Reactions,SADR)机理研究提供重要的参考依据。Serious adverse drug reactions caused by abacavir, an anti-AIDS drug, is proved be closely related to HLA-B＊5701 genetype. However, SADR caused by abacavir was seldom observed in those who carrying HLA-B＊5801. According to recent researches, the peptide binding to HLA-B＊5701 was involved in abacvair-induced SADR. Thus, the peptide-binding profile of HLA-B＊5701 is one of preconditions for exploring the mechanism of abacvair-induced SADR. Here, based on the structural description method of VHSE （Principal component score vector of hydrophobic, steric, and electronic properties）, support vector machine （SVM） together with the genetic algorithms （GA） is employed to establish classification models of peptide-binding affmifies of HLA-B＊5701 and B＇5801. The cross-validated sensitivity, specificity, area under receiver operating characteristics curve （AUC）, and matthews coefficient of correlation （MCC） of the optimal linear SVM model are 77.29%, 93.99%, 93.02%, 67.65% for HLA-B＊5701, and 78.08%, 89.62%, 88.34%, 64.73% for HLA-B＊5801. The external-validated sensitivity, specificity, AUC, and MCC are 80.02%, 94.53%, 94.62%, 72.09% for B＇5701, and 77.43%, 90.79%, 87.98%, 66.20% for B＇5801. Based on the weights of variables of the optimal classification models, detailed comparisons of peptide-binding affinities of HLA-B＊5701 with B＇5801 are also carried out. The results obtained by this paper can provide an important reference basis for the research of Abacvair-induced SADR.

关 键 词：阿巴卡韦 HLA-B~＊5701 HLA-B~＊5801 多肽 亲和活性 支持向量机 

分 类 号：O6-41[理学—化学]