PMID- 34659196 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20211214 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - A New Human Leukocyte Antigen Typing Algorithm Combined With Currently Available Genotyping Tools Based on Next-Generation Sequencing Data and Guidelines to Select the Most Likely Human Leukocyte Antigen Genotype. PG - 688183 LID - 10.3389/fimmu.2021.688183 [doi] LID - 688183 AB - BACKGROUND: High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate. MATERIALS AND METHODS: We compared availability, accuracy, correction score, and complementary ratio of eight HLA genotyping tools (OptiType, HLA-HD, PHLAT, seq2HLA, arcasHLA, HLAscan, HLA*LA, and Kourami) using 1,005 cases from the 1000 Genomes Project data. We created a new HLA-genotyping algorithm combining tools based on the precision and the accuracy of tools' combinations. Then, we assessed the new algorithm's performance in 39 in-house samples with normal whole-exome sequencing (WES) data and polymerase chain reaction-sequencing-based typing (PCR-SBT) results. RESULTS: Regardless of the type of tool, the calls presented by more than six tools concordantly showed high accuracy and precision. The accuracy of the group with at least six concordant calls was 100% (97/97) in HLA-A, 98.2% (112/114) in HLA-B, 97.3% (142/146) in HLA-C. The precision of the group with at least six concordant calls was over 98% in HLA-ABC. We additionally calculated the accuracy of the combination tools considering the complementary ratio of each tool and the accuracy of each tool, and the accuracy was over 98% in all groups with six or more concordant calls. We created a new algorithm that matches the above results. It was to select the HLA type if more than six out of eight tools presented a matched type. Otherwise, determine the HLA type experimentally through PCR-SBT. When we applied the new algorithm to 39 in-house cases, there were more than six matching calls in all HLA-A, B, and C, and the accuracy of these concordant calls was 100%. CONCLUSIONS: HLA genotyping accuracy using NGS data could be increased by combining the current HLA genotyping tools. This new algorithm could also be useful for preliminary screening to decide whether to perform an additional PCR-based experimental method instead of using tools with NGS data. CI - Copyright (c) 2021 Lee, Seo, Song, Song, Kim, Kim, Gong, Kim and Lee. FAU - Lee, Miseon AU - Lee M AD - Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. FAU - Seo, Jeong-Han AU - Seo JH AD - Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. AD - NeogenTC Corp, Seoul, South Korea. FAU - Song, Sungjae AU - Song S AD - NeogenTC Corp, Seoul, South Korea. FAU - Song, In Hye AU - Song IH AD - Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. FAU - Kim, Su Yeon AU - Kim SY AD - University of Ulsan College of Medicine, Seoul, South Korea. FAU - Kim, Young-Ae AU - Kim YA AD - NeogenTC Corp, Seoul, South Korea. FAU - Gong, Gyungyub AU - Gong G AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. FAU - Kim, Jeong Eun AU - Kim JE AD - Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. FAU - Lee, Hee Jin AU - Lee HJ AD - Department of Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. AD - NeogenTC Corp, Seoul, South Korea. AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211001 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA Antigens) SB - IM MH - *Algorithms MH - Clinical Decision-Making MH - Databases, Genetic MH - Genotype MH - HLA Antigens/*genetics/immunology MH - *High-Throughput Nucleotide Sequencing MH - Histocompatibility/*genetics MH - *Histocompatibility Testing MH - Humans MH - Immunotherapy MH - Neoplasms/*genetics/immunology/therapy MH - Phenotype MH - Predictive Value of Tests MH - Reproducibility of Results MH - Software PMC - PMC8517438 OTO - NOTNLM OT - HLA genotype OT - HLA typing algorithm OT - human leukocyte antigen (HLA) OT - immunotherapy OT - neoantigen OT - next-generation sequencing data (NGS) COIS- Authors SS and Y-AK were employed by company NeogenTC Corp. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/10/19 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/01/01 CRDT- 2021/10/18 08:55 PHST- 2021/03/30 00:00 [received] PHST- 2021/09/15 00:00 [accepted] PHST- 2021/10/18 08:55 [entrez] PHST- 2021/10/19 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.688183 [doi] PST - epublish SO - Front Immunol. 2021 Oct 1;12:688183. doi: 10.3389/fimmu.2021.688183. eCollection 2021.