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Record W4410003759 · doi:10.1101/2025.04.25.25326432

Array Genotyping of Transfusion Relevant Blood Cell Antigens in 6946 Ancestrally Diverse Subjects

2025· preprint· en· W4410003759 on OpenAlexaff
Nicholas Gleadall, Lianne Koets, Olga Shamardina, Jeremy Gollub, Orod Razeghi, Gorka Ochoa‐Garay, Jonathan Stephens, Ram Varma, Jennifer M. Martin, Elias Allara, Colin Brown, James Daly, Emanuele Di Angelantonio, Shane Grimsley, W. Martin Howell, Kati Hyvärinen, Ute Jentsch, Nathalie Kingston, Celina Montemayor, Celeste Moya-Valera, John Ord, Jukka Partanen, David J. Roberts, Kathleen Stirrups, Sunitha Vege, Andrea Harmer, Shantanu Kaushikkar, Willem H. Ouwehand, C. Ellen van der Schoot, Connie M. Westhoff, Barbera Veldhuisen, William J. Lane

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicBlood groups and transfusion
Canadian institutionsCanadian Blood ServicesNutrasource
FundersNIHR BioResourceStichting Sanquin BloedvoorzieningCambridge University HospitalsUniversity of CambridgeDepartment of Health and Social CareNIHR Cambridge Biomedical Research CentreBritish Heart FoundationNational Institute for Health and Care ResearchNHS Blood and Transplant
KeywordsGenotypingBlood group antigensBiologyAntigenPsychologyGeneticsGenotypeGene

Abstract

fetched live from OpenAlex

Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against non-self antigens remains a significant problem, particularly in frequently transfused patients. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythroid, platelet, leukocyte, and neutrophil antigens (HEA, HPA, HLA, and HNA, respectively) to support selection of blood products matched beyond ABO/Rh. Typing samples from 6946 donors of European, African, Admixed American, South Asian, and East Asian ancestry at two different laboratories showed a genotype reproducibility of ≥99% for 17 244 variants, translating to 99.98%, 99.90%, and 99.93% concordance across 338 372 HEA, 53 270 HPA, and 107 094 HLA genotypes, respectively. Compared to previous clinical typing data, concordance was 99.9% and 99.6% for 245 874 HEA and 3726 HPA comparisons, respectively. HLA types were 99.1% concordant with clinical typing across 8130 comparisons, with imputation accuracy higher in Europeans versus non-Europeans. Seven variant RHD alleles, a GYPB deletion underlying the U− phenotype, and 14 high-frequency antigen negative types were also detected. Beyond blood typing, hereditary hemochromatosis-associated HFE variants were identified in 276 donors. We found that the UBDT_PC1 array can reliably type a wide range of blood cell antigens across diverse ancestries. Reproducibility and accuracy were retained when transfusion-relevant targets from the UBDT_PC1 array were incorporated into the UKBB_v2.2 genome-wide typing array. The results represent the potential for significant advancement towards improved patient care by reducing harm in transfused patients through extended matching.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.260
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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