HLA单体型和HLA位点基因型预测模型的建立与验证  

Establishment and validation of prediction models for human leukocyte antigen haplotypes and human leukocyte antigen genotypes

作　　者：李杨[1] 杜丹 张腾腾[1] 韩颖 宋晔 袁晓妮[1] 鲍晓晶[1] 何军[1] Li Yang;Du Dan;Zhang Tengteng;Han Ying;Song Ye;Yuan Xiaoni;Bao Xiaojing;He Jun(Department of HLA Laboratory,Jiangsu Institute of Hematology,the First Affiliated Hospital of Soochow University,Suzhou 215031,China;China Marrow Donor Program,Beijing 100010,China)

机构地区：[1]苏州大学附属第一医院江苏省血液研究所HLA配型实验室,苏州215031 [2]中国造血干细胞捐献者资料库管理中心,北京100010

出　　处：《中华医学杂志》2024年第11期834-842,共9页National Medical Journal of China

基　　金：国家自然科学基金(82070180);江苏高校血液学协同创新中心项目(SX21100121)

摘　　要：目的建立人类白细胞抗原(HLA)单体型和HLA位点基因型预测模型,并验证预测模型的正确性。方法根据HLA单体型遗传及连锁不平衡规律,在获得发明专利和软件著作权的基础上,建立预测模型算法,主要包括:待预测数据预处理、与参考数据比对、预测结果过滤、概率计算和排序、置信度判断及预测结果输出。建立参考数据库包括HLA A-C-B-DRB1-DQB1高分辨单体型数据库、B-C和DRB1-DQB1连锁不平衡数据库,以及G组、NMDP Code等位基因对照表。选取已知A-C-B-DRB1-DQB1单体型和A、B、DRB1、C、DQB1高分辨基因型的数据进行预测,与已知结果比对,验证预测的正确性,分析正确性与预测结果概率分布、置信度的关系。结果建立了HLA单体型和HLA位点基因型预测模型,根据本研究技术路线建立完整的预测模型算法,包括根据HLA-A、B、DRB1、C、DQB1基因型预测A-C-B-DRB1-DQB1单体型;根据HLA-A、B、DRB1高分辨结果预测C、DQB1高分辨结果;根据HLA-A、B、DRB1中、低分辨结果预测A、B、DRB1和C,DQB1高分辨结果。“根据HLA-A、B、DRB1、C、DQB1基因型预测A-C-B-DRB1-DQB1单体型”模型验证结果:在787份验证数据中,740份预测正确,34份预测错误,13份未给出预测结果,预测正确率为94.0%(740/787);847份数据的预测正确率为100%(847/847)。将787、847份数据预测产出的2411、2594组单体型组合按置信度分组,置信度为1时正确率均为100%(48/48、114/114),置信度为2时正确率分别为96.2%(303/315)、97.8%(409/418)。根据HLA-A、B、DRB1高、中、低分辨结果预测A、B、DRB1和C、DQB1高分辨结果模型验证结果,使用以上共计1634份数据的A、B、DRB1高分辨结果预测C、DQB1高分辨结果,经与已知分型结果比对,预测结果中包含正确结果的比例为89.3%(1459/1634),其中,正确结果落在预测概率(GPP)排序前2位的比例为79.2%(1156/1459),落在前10位的比例达到95.0%(1386/1459)。根据预测组�Objective To establish prediction models for human leukocyte antigen(HLA)haplotypes and HLA genotypes,and verify the prediction accuracy.Methods The prediction models were established based on the characteristic of HLA haplotype inheritance and linkage disequilibrium(LD),as well as the invention patents and software copyrights obtained.The models include algorithm and reference databases such as HLA A-C-B-DRB1-DQB1 high-resolution haplotypes database,B-C and DRB1-DQB1 LD database,G group alleles table,and NMDP Code alleles table.The prediction algorithm involves data processing,comparison with reference data,filtering results,probability calculation and ranking,confidence degree estimation,and output of prediction results.The accuracy of the predictions was verified by comparing them with the correct results,and the relationship between prediction accuracy and the probability distribution and confidence degree of the predicted results was analyzed.Results The HLA haplotypes and genotypes prediction models were established.The prediction algorithm included the prediction of A-C-B-DRB1-DQB1 haplotypes according to HLA-A,B,DRB1,C,DQB1 genotypes,the prediction of C and DQB1 high-resolution results according to A,B and DRB1 high-resolution results,and the prediction of A,B,DRB1,C and DQB1 high resolution results according to the A,B and DRB1 intermediate or low resolution results.Validation results of"Predicting A-C-B-DRB1-DQB1 haplotypes basing on HLA-A,B,DRB1,C,DQB1 genotypes"model:for 787 data,the accuracy was 94.0%(740/787)with 740 correct predictions,34 incorrect predictions,and 13 instances with no predicted results.For 847 data,the accuracy was 100%(847/847).The 2411 and 2594 haplotype combinations predicted from 787 and 847 data were grouped according to confidence degree,the accuracy was 100%(48/48,114/114)for a confidence degree of 1,96.2%(303/315)and 97.8%(409/418)for a confidence degree of 2 respectively.Validation results of"Predicting A,B,DRB1 and C,DQB1 high-resolution genotypes basing on HLA-A,B,DRB1 h

关 键 词：人类白细胞抗原 多态性保守区段 单体型 连锁不平衡 预测模型 转化应用 

分 类 号：R394[医药卫生—医学遗传学]