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

Lane, William J.; Westhoff, Connie M.; Gleadall, Nicholas; Aguad, Maria; Smeland‐Wagman, Robin; Vege, Sunitha; Simmons, Daimon P.; Mah, Helen; Lebo, Matthew S.; Walter, Klaudia; Soranzo, Nicole; Angelantonio, Emanuele Di; Danesh, John; Roberts, David; Watkins, Nick; Ouwehand, Willem H.; Butterworth, Adam S.; Kaufman, Richard M.; Rehm, Heidi L.; Silberstein, Leslie E.; Green, Robert C; Bates, David W.; Blout, Carrie L.; Christensen, Kurt D.; Cirino, Allison L.; Ho, Carolyn Y.; Krier, Joel B.; Lehmann, Lisa Soleymani; MacRae, Calum A.; Morton, Cynthia C.; Perry, Denise; Seidman, Christine E.; Sunyaev, Shamil; Vassy, Jason L.; Schonman, Erica F.; Nguyen, Tiffany; Steffens, Eleanor; Betting, Wendi N.; Aronson, Samuel; Ceyhan‐Birsoy, Ozge; Machini, Kalotina; McLaughlin, Heather; Azzariti, Danielle R.; Tsai, Ellen; Blumenthal‐Barby, Jennifer; Feuerman, Lindsay Z.; McGuire, Amy L.; Lee, Kaitlyn; Robinson, Jill O.; Slashinski, Melody J.; Diamond, Pamela M.; Davis, Kelly Cue; Ubel, Peter A.; Kraft, Peter; Roberts, J. Scott; Garber, Judy E.; Hambuch, Tina; Murray, Michael F.; Kohane, Isaac S.; Kong, Sek Won

doi:10.1016/s2352-3026(18)30053-x

Cited by 76 publications

(151 citation statements)

References 36 publications

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“…) . ABO was also excluded from this analysis, as accurate prediction of this phenotype often requires precise phasing algorithms …”

Section: Resultsmentioning

confidence: 99%

“…Analysis of structural variations from the 1000 Genomes Project has been published, but its precision is limited . Homologous genes also pose the risk of misalignment of the short NGS reads produced by this project, and their accurate immunohematology interpretation may require locus‐specific adjustment of filter thresholds, as illustrated by recent publications . Thus, in the absence of experimental validation data and targeted filter adjustment, structural variants greater than 50 bp and homologous blood group genes with known recombination events ( RHD, RHCE, GYPA, GYPB, and GYPE ) were deferred from this study.…”

Section: Discussionmentioning

confidence: 99%

“…A number of successful clinical applications have been reported, and further efforts are under way in the areas of oncology, hemostasis, obstetrics, and pharmacology to identify the clinical benefits of genomic medicine . Transfusion medicine is an additional discipline with a strong genetics foundation that is exploring this approach …”

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confidence: 99%

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Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

et al. 2018

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BACKGROUND The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance. STUDY DESIGN AND METHODS The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next‐generation sequencing output files into a predicted red blood cell (RBC) phenotype. RESULTS Forty‐two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull‐down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious. CONCLUSION Next‐generation sequencing has known potential for high‐throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.

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“…) . ABO was also excluded from this analysis, as accurate prediction of this phenotype often requires precise phasing algorithms …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

et al. 2018

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“…The proof of principle study by Lane et al () showed that these challenges can be managed. The next step was to improve and automate the data analysis for blood group profiling as described in the next two sections (Moller et al , ; Lane et al , ).…”

Section: Complete Blood Group Profiles From Wgs Datamentioning

confidence: 99%

“…A small number of complex RH hybrids were correctly defined by the refined algorithm although there is still a need for validation on more complex samples, including samples from diverse ethnic backgrounds (Lane et al , ; Flower et al , ).…”

Section: Automated Typing Algorithms For Blood Group Profilingmentioning

confidence: 99%

Developments beyond blood group serology in the genomics era

2019

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Summary Blood group serology and single nucleotide polymorphism‐based genotyping platforms are accurate but do not provide a comprehensive cover for all 36 blood group systems and do not cover the antigen diversity observed among population groups. This review examines the extent to which genomics is shaping blood group serology. Resources for genomics include the Human Reference Genome Sequence assembly; curated blood group tables listing variants; public databases providing information on genetic variants from world‐wide studies; and massively parallel sequencing technologies. Blood group genomic studies span the spectrum, from bioinformatic data mining of huge data sets containing whole genome and whole exome information to laboratory investigations utilising targeted sequencing approaches. Blood group predictions based on genome sequencing and genomic studies are proving accurate, and have shown utility in both research and reference settings. Overall, studies confirm the potential for blood group genomics to reshape donor and patient transfusion management strategies to provide more compatible blood transfusions.

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Genome Reporting for Healthy Populations—Pipeline for Genomic Screening from the GENCOV COVID‐19 Study

et al. 2022

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Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS‐CoV‐2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS‐CoV‐2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID‐19, including HLA genotyping, large‐scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases—coronary artery disease; atrial fibrillation; type‐2 diabetes; and breast, prostate, and colon cancer—as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large‐scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup

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

Abstract: National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Cited by 76 publications

References 36 publications

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Developments beyond blood group serology in the genomics era

Genome Reporting for Healthy Populations—Pipeline for Genomic Screening from the GENCOV COVID‐19 Study

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