基于TAP分子亲和力模型预测MHCⅠ类分子提呈短肽的免疫原性  

Immunogenicity Prediction of The Peptides Presented by MHCⅠ Molecules Based on The TAP Binding Affinity Model

作　　者：盛浩 卢玉峰[2] 包永明[3] SHENG Hao;LU Yu-Feng;BAO Yong-Ming(College of Sciences,Liaoning Shihua University,Fushun 113001,China;School of Mathematical Sciences,Dalian University of Technology,Dalian 116023,China;School of Life Science and Biotechnology,Dalian University of Technology,Dalian 116023,China)

机构地区：[1]辽宁石油化工大学理学院,抚顺113001 [2]大连理工大学数学科学学院,大连116023 [3]大连理工大学生命科学与技术学院,大连116023

出　　处：《生物化学与生物物理进展》2020年第2期157-168,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金基金(61602228);辽宁省自然科学基金(L2017LQN03);辽宁石油化工大学启动基金(1100140109)资助项目~~

摘　　要：主要组织相容性复合体(major histocompatibility complex,MHC)Ⅰ类分子亲和力模型有助于筛选出候选短肽,为实验确定可以与MHCⅠ类分子形成复合物从而激活细胞毒性T细胞的短肽提供帮助;抗原处理相关转运体(transporter associated with antigen processing,TAP)分子亲和力模型也可用于筛选候选短肽;如何更好利用两类亲和力模型筛选出候选短肽、这两类亲和力模型对短肽选择性的异同以及这种选择性异同的生物学机制尚不清楚.本文重新整理了TAP亲和力测试集,使训练样本达到699个;使用核函数平衡矩阵算法建立的TAP亲和力模型预测精度高于同类算法,5折交叉检验Pearson相关系数0.89;结合HLA A3分子亲和力模型、TAP亲和力模型显著提高免疫原性短肽预测精度,AUC值从~0.82上升到0.87.提高的原因是两个亲和力模型对第2、9位置"最佳"氨基酸不同偏好性和这种不同偏好的互补性造成的.TAP分子与短肽模拟对接结果反映了这个结论.TAP亲和力可在线预测(http://www.bilologymaths.top/mbtwo/major.aspx).The major histocompatibility complex(MHC)Ⅰbinding affinity models have contributed to screen the candidate peptides,and have assisted the experiments in determining the peptides that can form complexes with MHCⅠmolecules to activate cytotoxic T cells.The transporter associated with antigen processing(TAP)binding models could also be used for screening the candidate peptides.How to make the best of the two types of binding affinity models for screening out the candidate peptides,the similarities and differences between the selectivity of TAP and MHCⅠmolecules in peptides and the biological mechanism of that similarities and differences,these three questions remains obscure.Herein,we rearranged the TAP binding test set,increasing its size to 699.The established TAP binding model based on Kernel-function stabilized matrix method(KSMM)had a higher prediction accuracy than that of the state of the art,achieving a relevant correlation coefficient of 0.89 on a 5-fold cross-validation.The integrative prediction of HLA-A3 affinity and TAP affinity models remarkedly improved the discrimination accuracy,with the AUC value increasing from^0.82 to 0.87.This improvement is due to the different preferences of the two types of affinity models for the best defined amino acids on 2 nd and 9 th positions,as well as to the complementarity of such different preferences.The results of TAP-peptide docking also supported this conclusion.The TAP model is available online:http://www.bilologymaths.top/mbtwo/major.aspx.

关 键 词：免疫原性 细胞毒性T细胞 MHCⅠ类分子 抗原处理相关转运体 核函数平衡矩阵方法 

分 类 号：R34[医药卫生—基础医学] R35