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. 2020 Aug;81(8):423-429.
doi: 10.1016/j.humimm.2020.06.002. Epub 2020 Jun 13.

Concordance between predicted HLA type using next generation sequencing data generated for non-HLA purposes and clinical HLA type

Ann M Moyer  1 , Brian Dukek  1 , Patti Duellman  1 , Brittany Schneider  1 , Laurie Wakefield  1 , Jennifer M Skierka  1 , Rajeswari Avula  1 , Aditya V Bhagwate  2 , Krishna R Kalari  2 , Justin D Kreuter  1 , Matthew P Goetz  3 , Judy C Boughey  4 , John L Black 3rd  1 , Manish J Gandhi  5
Affiliations

Concordance between predicted HLA type using next generation sequencing data generated for non-HLA purposes and clinical HLA type

Ann M Moyer et al. Hum Immunol. 2020 Aug.

Abstract

We explored the feasibility of obtaining accurate HLA type using pre-existing NGS data not generated for HLA purposes. 83 exomes and 500 _targeted NGS pharmacogenomic panels were analyzed using Omixon HLA Explore, OptiType, and/or HLA-Genotyper software. Results were compared against clinical HLA genotyping. 765 (94.2%) Omixon and 769 (94.7%) HLA-Genotyper of 812 germline allele calls across class I/II loci and 402 (99.5%) of 404 OptiType class I calls were concordant to the second field (i.e. HLA-A*02:01). An additional 19 (2.3%) Omixon, 39 (4.8%) HLA-Genotyper, and 2 (0.5%) OptiType allele calls were first field concordant (i.e. HLA-A*02). Using Omixon, four alleles (0.4%) were discordant and 24 (3.0%) failed to call, while 4 alleles (0.4%) were discordant using HLA-Genotyper. Tumor exomes were also evaluated and were 85.4%, 91.6%, and 100% concordant (Omixon and HLA-Genotyper with 96 alleles tested, and Optitype with 48 class I alleles, respectively). The 15 exomes and 500 pharmacogenomic panels were 100% concordant for each pharmacogenomic allele tested. This work has broad implications spanning future clinical care (pharmacogenomics, tumor response to immunotherapy, autoimmunity, etc.) and research applications.

Keywords: Exome; HLA; Human leukocyte antigen; MHC; Next generation sequencing; Pharmacogenetics; Pharmacogenomics.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
(A) HLA-B allele alignment of next generation sequencing data for one sample in HLA Explore software (exons 1–4). This sample resulted in a failure or “no call” for the HLA-B locus; however, by actual HLA typing was found to be HLA-B*44:02:01/*56:01:01. The top row shows the correct alignment of reads (represented by stacked grey bars) to the HLA-B*56:01:01 allele from exon 1 (left side) to exon 4 (right side of diagram), while the middle row shows reads unevenly and incorrectly mapping to the HLA-B*83:01 allele, and the bottom row shows a lack of reads mapping to the correct HLA-B*44:02:01 allele. (B) In contrast, the Optitype plots for the same sample are shown. This software produced a call concordant to the second field for each allele.
Fig. 2.
Fig. 2.
Average coverage (number of reads) mapping to each HLA gene in exome sequencing data obtained for breast cancer research and not enriched for the HLA region.
See this image and copyright information in PMC

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