Lane WJ, et al. - Given that patients who require multiple transfusions can suffer sensitization to antigens after blood transfusion and typing for ABO and Rh—the most important blood groups—cannot be done with single-nucleotide polymorphism (SNP) typing alone, researchers developed a new method based on whole-genome sequencing to identify red blood cell (RBC) and platelet antigens. Antigen typing based on whole-genome sequencing allowed more precise antigen-matching of patients with blood donors and hence affords a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.

Methods

• Researchers performed this whole-genome sequencing study which represents a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial with no measured patient outcomes.
• A database of molecular changes in RBC and platelet antigens was created.
• Based on whole-genome sequencing (bloodTyper), an automated antigen-typing algorithm was developed.
• In order to address cis–trans haplotype ambiguities and homologous gene alignments, this algorithm was iteratively improved.
• They used whole-genome sequencing data from 110 MedSeq participants (30 × depth) to initially validate bloodTyper via comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens.
• With whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons, further validation of bloodTyper was done.

Results

• Iterative improvement in bloodTyper was brought about by comparing its typing results with conventional serological and SNP typing in three rounds of testing.
• Across the first 20 MedSeq genomes, the initial whole-genome sequencing typing algorithm was found to be 99·5% concordant.
• Development of an improved algorithm resulted from addressing discordances.
• This improved algorithm was found to be 99·8% concordant for the remaining 90 MedSeq genomes.
• Data showed that additional modifications led to the final algorithm.
• This final algorithm was noted to be 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).