Dataset Information

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

ABSTRACT: BACKGROUND:There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. METHODS:This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30?×?depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15?×?depth) with serological comparisons. FINDINGS:We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). INTERPRETATION:By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. FUNDING:National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

SUBMITTER: Lane WJ

PROVIDER: S-EPMC6438177 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

Lane William J WJ Westhoff Connie M CM Gleadall Nicholas S NS Aguad Maria M Smeland-Wagman Robin R Vege Sunitha S Simmons Daimon P DP Mah Helen H HH Lebo Matthew S MS Walter Klaudia K Soranzo Nicole N Di Angelantonio Emanuele E Danesh John J Roberts David J DJ Watkins Nick A NA Ouwehand Willem H WH Butterworth Adam S AS Kaufman Richard M RM Rehm Heidi L HL Silberstein Leslie E LE Green Robert C RC

The Lancet. Haematology 20180517 6

<h4>Background</h4>There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) ...[more]

PMID: 29780001

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Dataset Information

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

Publications

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

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