PMID- 29334893 OWN - NLM STAT- MEDLINE DCOM- 20180711 LR - 20181113 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 19 IP - 1 DP - 2018 Jan 15 TI - High-sensitivity HLA typing by Saturated Tiling Capture Sequencing (STC-Seq). PG - 50 LID - 10.1186/s12864-018-4431-5 [doi] LID - 50 AB - BACKGROUND: Highly polymorphic human leukocyte antigen (HLA) genes are responsible for fine-tuning the adaptive immune system. High-resolution HLA typing is important for the treatment of autoimmune and infectious diseases. Additionally, it is routinely performed for identifying matched donors in transplantation medicine. Although many HLA typing approaches have been developed, the complexity, low-efficiency and high-cost of current HLA-typing assays limit their application in population-based high-throughput HLA typing for donors, which is required for creating large-scale databases for transplantation and precision medicine. RESULTS: Here, we present a cost-efficient Saturated Tiling Capture Sequencing (STC-Seq) approach to capturing 14 HLA class I and II genes. The highly efficient capture (an approximately 23,000-fold enrichment) of these genes allows for simplified allele calling. Tests on five genes (HLA-A/B/C/DRB1/DQB1) from 31 human samples and 351 datasets using STC-Seq showed results that were 98% consistent with the known two sets of digitals (field1 and field2) genotypes. Additionally, STC can capture genomic DNA fragments longer than 3 kb from HLA loci, making the library compatible with the third-generation sequencing. CONCLUSIONS: STC-Seq is a highly accurate and cost-efficient method for HLA typing which can be used to facilitate the establishment of population-based HLA databases for the precision and transplantation medicine. FAU - Jiao, Yang AU - Jiao Y AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Li, Ran AU - Li R AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Wu, Chao AU - Wu C AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Ding, Yibin AU - Ding Y AD - School of Mathematical Science, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Liu, Yanning AU - Liu Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China. FAU - Jia, Danmei AU - Jia D AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Wang, Lifeng AU - Wang L AD - Beijing Ming-tian Genetics Ltd, Beijing, 100070, People's Republic of China. FAU - Xu, Xiang AU - Xu X AD - School of Mathematical Science, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. FAU - Zhu, Jing AU - Zhu J AD - Beijing Ming-tian Genetics Ltd, Beijing, 100070, People's Republic of China. jingzh76@gmail.com. FAU - Zheng, Min AU - Zheng M AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China. minzheng@zju.edu.cn. AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China. minzheng@zju.edu.cn. FAU - Jia, Junling AU - Jia J AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. junlingjia@zju.edu.cn. AD - Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. junlingjia@zju.edu.cn. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China. junlingjia@zju.edu.cn. LA - eng GR - No.2016YFC0902702/National Program on Key Research Project of China/International GR - 2017YFA0104901/National Program on Key Research Project of China/International GR - LR15C060001/Nature Science Foundation of Zhejiang Province/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180115 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (HLA Antigens) SB - IM MH - HLA Antigens/genetics MH - *High-Throughput Nucleotide Sequencing MH - Histocompatibility Testing/*methods MH - Humans MH - *Sequence Analysis, DNA PMC - PMC5769328 OTO - NOTNLM OT - HLA typing OT - Human leukocyte antigen (HLA) OT - Hybridization capture OT - Next-generation sequencing (NGS) OT - Third-generation sequencing COIS- ETHICS APPROVAL: Our work did not involve any human and animal tissue. This study has been approved by the ethics committee of the First Affiliated Hospital, School of Medicine, Zhejiang University. Dan Du from the China Marrow Donor Program gave the permission for this study to use their validated DNA samples. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: Zhejiang University submitted a patent application on the method described in this paper 12/27/2017. EDAT- 2018/01/18 06:00 MHDA- 2018/07/12 06:00 PMCR- 2018/01/15 CRDT- 2018/01/17 06:00 PHST- 2017/10/20 00:00 [received] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/01/17 06:00 [entrez] PHST- 2018/01/18 06:00 [pubmed] PHST- 2018/07/12 06:00 [medline] PHST- 2018/01/15 00:00 [pmc-release] AID - 10.1186/s12864-018-4431-5 [pii] AID - 4431 [pii] AID - 10.1186/s12864-018-4431-5 [doi] PST - epublish SO - BMC Genomics. 2018 Jan 15;19(1):50. doi: 10.1186/s12864-018-4431-5.