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Record W3163949076 · doi:10.1038/s42003-021-01989-3

High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation

2021· article· en· W3163949076 on OpenAlexafffund
Jenny Tran, Oliver P. Günther, Karen Sherwood, Franz Fenninger, Lenka L. Allan, James H. Lan, Ruth Sapir‐Pichhadze, René J. Duquesnoy, Frans H.J. Claas, Steven G. E. Marsh, W. Robert McMaster, Paul Keown, Stirling Bryan, Timothy Caulfield, Karim Oualkacha, Kathryn Tinckam, Robert Liwski, Patricia Campbell, Héloïse Cardinal, Sacha A. De Serres, Chee Loong Saw, Michael Mengel, B. Sis, Éric Wagner, Noureddine Berka, Bruce M. McManus, Marie‐Josée Hébert, Leonard J. Foster, Fábio Rossi, Christoph H. Borchers, Ciriaco A. Piccirillo, Constantin Polychronakos, Raymond T. Ng, Anthony M. Jevnikar, Pieter R. Cullis, Guido Filler, Harvey Wong, Bethany J. Foster, John C. Gill, S. Joseph Kim, Lee Anne Tibbles, Atul Humar, Steven M. Shechter, Prosanto Chaudhury, Nicolás Fernández, Elizabeth Fowler, Bryce Kiberd, Jagbir Gill, Marie‐Chantal Fortin, Scott Klarenbach, Robert Balshaw, Seema Mital, István Mucsi, David N. Ostrow, C. R. Stiller, Rulan S. Parekh, Lucie Richard, Lynne Senécal, Tom Blydt‐Hansen, Howard M. Gebel, Eric T. Weimer, Bruce Kaplan, Gilbert J. Burckart, Derek Middleton, Marcel G.J. Tilanus, Teun van Gelder, Gerhard Opelz, Michael Oellerich, Pierre Marquet, Carlo A. Marra, Zoltán Kaló

Bibliographic record

VenueCommunications Biology · 2021
Typearticle
Languageen
FieldMedicine
TopicRenal Transplantation Outcomes and Treatments
Canadian institutionsHéma-QuébecSickKids FoundationUniversity of ManitobaGeorge & Fay Yee Centre for Healthcare InnovationUniversity of CalgaryUniversité LavalUniversité du Québec à MontréalToronto General HospitalInstitute of Infection and ImmunityUniversity Health NetworkDalhousie UniversityWestern UniversityUniversity of TorontoHospital for Sick ChildrenUniversité de MontréalUniversity of AlbertaUniversity of British Columbia HospitalMcGill University Health CentreMcGill UniversityKidney Foundation of CanadaUniversity of British Columbia
FundersGenome AlbertaCanadian Institutes of Health ResearchGenome British ColumbiaGenome Canada
KeywordsHuman leukocyte antigenTransplantationIn silicoEpitopeHistocompatibility TestingComputational biologyPopulationImmunologyDNA sequencingMatching (statistics)GeneBiologyAntibodyAntigenMedicineGeneticsInternal medicinePathology

Abstract

fetched live from OpenAlex

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms. Simulations of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.069
Threshold uncertainty score0.377

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.050
GPT teacher head0.331
Teacher spread0.280 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations17
Published2021
Admission routes2
Has abstractyes

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