PMID- 31832057 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231019 IS - 1660-3796 (Print) IS - 1660-3818 (Electronic) IS - 1660-3796 (Linking) VI - 46 IP - 5 DP - 2019 Oct TI - Bioinformatics Strategies, Challenges, and Opportunities for Next Generation Sequencing-Based HLA Genotyping. PG - 312-325 LID - 10.1159/000502487 [doi] AB - The advent of next generation sequencing (NGS) has altered the face of genotyping the human leukocyte antigen (HLA) system in clinical, stem cell donor registry, and research contexts. NGS has led to a dramatically increased sequencing throughput at high accuracy, while being more time and cost efficient than precursor technologies. This has led to a broader and deeper profiling of the key genes in the human immunogenetic make-up. The rapid evolution of sequencing technologies is evidenced by the development of varied short-read sequencing platforms with differing read lengths and sequencing capacities to long-read sequencing platforms capable of profiling full genes without fragmentation. Concomitantly, there has been development of a diverse set of computational analyses and software tools developed to deal with the various strengths and limitations of the sequencing data generated by the different sequencing platforms. This review surveys the different modalities involved in generating NGS HLA profiling sequence data. It systematically describes various computational approaches that have been developed to achieve HLA genotyping to different degrees of resolution. At each stage, this review enumerates the drawbacks and advantages of each of the platforms and analysis approaches, thus providing a comprehensive picture of the current state of HLA genotyping technologies. CI - Copyright (c) 2019 by S. Karger AG, Basel. FAU - Klasberg, Steffen AU - Klasberg S AD - DKMS Life Science Lab, Dresden, Germany. FAU - Surendranath, Vineeth AU - Surendranath V AD - DKMS Life Science Lab, Dresden, Germany. FAU - Lange, Vinzenz AU - Lange V AD - DKMS Life Science Lab, Dresden, Germany. FAU - Schofl, Gerhard AU - Schofl G AD - DKMS Life Science Lab, Dresden, Germany. LA - eng PT - Journal Article PT - Review DEP - 20190906 PL - Switzerland TA - Transfus Med Hemother JT - Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie JID - 101176417 PMC - PMC6876610 OTO - NOTNLM OT - Genotyping OT - Human leukocyte antigen OT - Next generation sequencing COIS- The authors have no conflicts of interest to declare. EDAT- 2019/12/14 06:00 MHDA- 2019/12/14 06:01 PMCR- 2019/09/06 CRDT- 2019/12/14 06:00 PHST- 2019/05/12 00:00 [received] PHST- 2019/07/30 00:00 [accepted] PHST- 2019/12/14 06:00 [entrez] PHST- 2019/12/14 06:00 [pubmed] PHST- 2019/12/14 06:01 [medline] PHST- 2019/09/06 00:00 [pmc-release] AID - tmh-0046-0312 [pii] AID - 10.1159/000502487 [doi] PST - ppublish SO - Transfus Med Hemother. 2019 Oct;46(5):312-325. doi: 10.1159/000502487. Epub 2019 Sep 6.