PMID- 29940840 OWN - NLM STAT- MEDLINE DCOM- 20190213 LR - 20230926 IS - 1471-2105 (Electronic) IS - 1471-2105 (Linking) VI - 19 IP - 1 DP - 2018 Jun 25 TI - Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios. PG - 239 LID - 10.1186/s12859-018-2239-6 [doi] LID - 239 AB - BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods. RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles. CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential. FAU - Matey-Hernandez, Maria Luisa AU - Matey-Hernandez ML AD - Center for Biological Sequence Analysis, Department of Bio and Health Informatics, Technical University of Denmark, DK-2800, Lyngby, Denmark. AD - Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK. CN - Danish Pan Genome Consortium FAU - Brunak, Soren AU - Brunak S AD - Center for Biological Sequence Analysis, Department of Bio and Health Informatics, Technical University of Denmark, DK-2800, Lyngby, Denmark. AD - Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. FAU - Izarzugaza, Jose M G AU - Izarzugaza JMG AUID- ORCID: 0000-0003-1754-5122 AD - Center for Biological Sequence Analysis, Department of Bio and Health Informatics, Technical University of Denmark, DK-2800, Lyngby, Denmark. josemgizarzugaza@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180625 PL - England TA - BMC Bioinformatics JT - BMC bioinformatics JID - 100965194 RN - 0 (HLA Antigens) SB - IM MH - Benchmarking/*methods MH - Family MH - Genomics/*methods MH - Genotyping Techniques/*methods MH - HLA Antigens/*genetics MH - Histocompatibility Testing MH - Humans MH - Parents MH - Sweden PMC - PMC6019707 OTO - NOTNLM OT - Clinical genomics OT - HLA genotyping OT - NGS OT - Population genetics OT - Prediction COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The parent-offspring trios (mother-father-child) in the Danish Pan-Genome were selected from the Copenhagen Family Bank [35, 48]. The study protocol was reviewed and approved by The Danish National Committee on Health Research Ethics (file number 1210920, submission numbers 36615 and 38259), as described in [36]. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. 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FIR - Maretty, Lasse IR - Maretty L FIR - Jensen, Jacob Malte IR - Jensen JM FIR - Petersen, Bent IR - Petersen B FIR - Sibbesen, Jonas Andreas IR - Sibbesen JA FIR - Liu, Siyang IR - Liu S FIR - Villesen, Palle IR - Villesen P FIR - Skov, Laurits IR - Skov L FIR - Belling, Kirstine IR - Belling K FIR - Have, Christian Theil IR - Have CT FIR - Izarzugaza, Jose M G IR - Izarzugaza JMG FIR - Grosjean, Marie IR - Grosjean M FIR - Bork-Jensen, Jette IR - Bork-Jensen J FIR - Grove, Jakob IR - Grove J FIR - Als, Thomas D IR - Als TD FIR - Huang, Shujia IR - Huang S FIR - Chang, Yuqi IR - Chang Y FIR - Xu, Ruiqi IR - Xu R FIR - Ye, Weijian IR - Ye W FIR - Rao, Junhua IR - Rao J FIR - Guo, Xiaosen IR - Guo X FIR - Sun, Jihua IR - Sun J FIR - Cao, Hongzhi IR - Cao H FIR - Ye, Chen IR - Ye C FIR - V Beusekom, Johan IR - V Beusekom J FIR - Espeseth, Thomas IR - Espeseth T FIR - Flindt, Esben IR - Flindt E FIR - Friborg, Rune M IR - Friborg RM FIR - Halager, Anders E IR - Halager AE FIR - Le Hellard, Stephanie IR - Le Hellard S FIR - Hultman, Christina M IR - Hultman CM FIR - Lescai, Francesco IR - Lescai F FIR - Li, Shengting IR - Li S FIR - Lund, Ole IR - Lund O FIR - Longren, Peter IR - Longren P FIR - Mailund, Thomas IR - Mailund T FIR - Matey-Hernandez, Maria Luisa IR - Matey-Hernandez ML FIR - Mors, Ole IR - Mors O FIR - Pedersen, Christian N S IR - Pedersen CNS FIR - Sicheritz-Ponten, Thomas IR - Sicheritz-Ponten T FIR - Sullivan, Patrick IR - Sullivan P FIR - Syed, Ali IR - Syed A FIR - Westergaard, David IR - Westergaard D FIR - Yadav, Rachita IR - Yadav R FIR - Li, Ning IR - Li N FIR - Xu, Xun IR - Xu X FIR - Hansen, Torben IR - Hansen T FIR - Krogh, Anders IR - Krogh A FIR - Bolund, Lars IR - Bolund L FIR - Sorensen, Thorkild I A IR - Sorensen TIA FIR - Pedersen, Oluf IR - Pedersen O FIR - Gupta, Ramneek IR - Gupta R FIR - Rasmussen, Simon IR - Rasmussen S FIR - Besenbacher, Soren IR - Besenbacher S FIR - Borglum, Anders D IR - Borglum AD FIR - Wang, Jun IR - Wang J FIR - Eiberg, Hans IR - Eiberg H FIR - Kristiansen, Karsten IR - Kristiansen K FIR - Brunak, Soren IR - Brunak S FIR - Schierup, Mikkel Heide IR - Schierup MH EDAT- 2018/06/27 06:00 MHDA- 2019/02/14 06:00 PMCR- 2018/06/25 CRDT- 2018/06/27 06:00 PHST- 2018/03/01 00:00 [received] PHST- 2018/06/12 00:00 [accepted] PHST- 2018/06/27 06:00 [entrez] PHST- 2018/06/27 06:00 [pubmed] PHST- 2019/02/14 06:00 [medline] PHST- 2018/06/25 00:00 [pmc-release] AID - 10.1186/s12859-018-2239-6 [pii] AID - 2239 [pii] AID - 10.1186/s12859-018-2239-6 [doi] PST - epublish SO - BMC Bioinformatics. 2018 Jun 25;19(1):239. doi: 10.1186/s12859-018-2239-6.