RBCeq: A robust and scalable algorithm for accurate genetic blood typing
Sudhir Jadhao,
Candice L. Davison,
Eileen V. Roulis,
Elizna M. Schoeman,
Mayur Divate,
Mitchel Haring,
Chris Williams,
Arvind Jaya Shankar,
Simon Lee,
Natalie M. Pecheniuk,
David O Irving,
Catherine A. Hyland,
Robert L. Flower,
Shivashankar H. Nagaraj
Affiliations
Sudhir Jadhao
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Corresponding author.
Candice L. Davison
Australian Red Cross Lifeblood Research and Development, Brisbane, Queensland, Australia
Eileen V. Roulis
Australian Red Cross Lifeblood Research and Development, Brisbane, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia
Elizna M. Schoeman
Australian Red Cross Lifeblood Research and Development, Brisbane, Queensland, Australia
Mayur Divate
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia
Mitchel Haring
Office of eResearch, Queensland University of Technology, Brisbane, Queensland 4059, Australia
Chris Williams
Office of eResearch, Queensland University of Technology, Brisbane, Queensland 4059, Australia
Arvind Jaya Shankar
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia
Simon Lee
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia
Natalie M. Pecheniuk
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
David O Irving
Research and Development, Australian Red Cross Blood Service, Sydney, New South Wales, Australia
Catherine A. Hyland
Australian Red Cross Lifeblood Research and Development, Brisbane, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia
Robert L. Flower
Australian Red Cross Lifeblood Research and Development, Brisbane, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia
Shivashankar H. Nagaraj
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Brisbane, Australia
Summary: Background: While blood transfusion is an essential cornerstone of hematological care, patients requiring repetitive transfusion remain at persistent risk of alloimmunization due to the diversity of human blood group polymorphisms. Despite the promise, user friendly methods to accurately identify blood types from next-generation sequencing data are currently lacking. To address this unmet need, we have developed RBCeq, a novel genetic blood typing algorithm to accurately identify 36 blood group systems. Methods: RBCeq can predict complex blood groups such as RH, and ABO that require identification of small indels and copy number variants. RBCeq also reports clinically significant, rare, and novel variants with potential clinical relevance that may lead to the identification of novel blood group alleles. Findings: The RBCeq algorithm demonstrated 99·07% concordance when validated on 402 samples which included 29 antigens with serology and 9 antigens with SNP-array validation in 14 blood group systems and 59 antigens validation on manual predicted phenotype from variant call files. We have also developed a user-friendly web server that generates detailed blood typing reports with advanced visualization (https://www.rbceq.org/). Interpretation: RBCeq will assist blood banks and immunohematology laboratories by overcoming existing methodological limitations like scalability, reproducibility, and accuracy when genotyping and phenotyping in multi-ethnic populations. This Amazon Web Services (AWS) cloud based platform has the potential to reduce pre-transfusion testing time and to increase sample processing throughput, ultimately improving quality of patient care. Funding: This work was supported in part by Advance Queensland Research Fellowship, MRFF Genomics Health Futures Mission (76,757), and the Australian Red Cross LifeBlood. The Australian governments fund the Australian Red Cross Lifeblood for the provision of blood, blood products and services to the Australian community.
