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. 2020 Nov 12;15(11):e0242168.
doi: 10.1371/journal.pone.0242168. eCollection 2020.

Blood group typing from whole-genome sequencing data

Julien Paganini  1 , Peter L Nagy  2 , Nicholas Rouse  2 , Philippe Gouret  1 , Jacques Chiaroni  3 , Chistophe Picard  3 , Julie Di Cristofaro  3
Affiliations

Blood group typing from whole-genome sequencing data

Julien Paganini et al. PLoS One. .

Abstract

Many questions can be explored thanks to whole-genome data. The aim of this study was to overcome their main limits, software availability and database accuracy, and estimate the feasibility of red blood cell (RBC) antigen typing from whole-genome sequencing (WGS) data. We analyzed whole-genome data from 79 individuals for HLA-DRB1 and 9 RBC antigens. Whole-genome sequencing data was analyzed with software allowing phasing of variable positions to define alleles or haplotypes and validated for HLA typing from next-generation sequencing data. A dedicated database was set up with 1648 variable positions analyzed in KEL (KEL), ACKR1 (FY), SLC14A1 (JK), ACHE (YT), ART4 (DO), AQP1 (CO), CD44 (IN), SLC4A1 (DI) and ICAM4 (LW). Whole-genome sequencing typing was compared to that previously obtained by amplicon-based monoallelic sequencing and by SNaPshot analysis. Whole-genome sequencing data were also explored for other alleles. Our results showed 93% of concordance for blood group polymorphisms and 91% for HLA-DRB1. Incorrect typing and unresolved results confirm that WGS should be considered reliable with read depths strictly above 15x. Our results supported that RBC antigen typing from WGS is feasible but requires improvements in read depth for SNV polymorphisms typing accuracy. We also showed the potential for WGS in screening donors with rare blood antigens, such as weak JK alleles. The development of WGS analysis in immunogenetics laboratories would offer personalized care in the management of RBC disorders.

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Conflict of interest statement

The authors have no conflicts of interest to declare. Commercial affiliation of JP, PG and PN does not alter our adherence to all PLOS ONE policies on sharing data and materials.

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