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Record W4205129588 · doi:10.1101/2022.01.13.475872

The immunopeptidome from a genomic perspective: Establishing immune-relevant regions for cancer vaccine design

2022· preprint· en· W4205129588 on OpenAlexaff
Georges Bedran, Tongjie Wang, Dominika Pankanin, Kenneth Weke, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Cátia Pesquita, Håkan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Pałkowski, Maciej Pawlik, Maciej Parys, J. Robert O’Neill, Paul M. Brennan, Stefan Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fåhræus, Ted R. Hupp, Sachin Kote, Javier A. Alfaro

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topicvaccines and immunoinformatics approaches
Canadian institutionsUniversity of Victoria
FundersEuropean Regional Development FundHorizon 2020 Framework ProgrammeFundação para a Ciência e a TecnologiaInfrastruktura PL-GridAgence Nationale de la RechercheCancerfondenFundacja na rzecz Nauki PolskiejEuropean Commission
KeywordsImmunogenicityCancer vaccineCancer immunotherapyBiologyMajor histocompatibility complexImmune systemMHC class IComputational biologyAntigenEpitopePopulationImmunotherapyCancerHuman leukocyte antigenGenomicsGenomeGeneticsImmunologyGeneMedicine

Abstract

fetched live from OpenAlex

Abstract A longstanding disconnect between the growing number of MHC Class I immunopeptidomic studies and genomic medicine hinders cancer vaccine design. We develop COD-dipp to genomically map the full spectrum of detected canonical and non-canonical (non-exonic) MHC Class I antigens from 26 cancer studies. We demonstrate that patient mutations in regions overlapping physically identified antigens better predict immunotherapy response when compared to neoantigen predictions. We suggest a vaccine design approach using 140,966 highly immune-visible regions of the genome annotated by their expression and haplotype frequency in the human population. These regions tend to be highly conserved, mutated in cancer and harbor 7.8 times more immunogenicity. Intersecting pan-cancer mutations with these immune surveilled regions revealed a potential to create off-the-shelf multi-epitope vaccines against public neoantigens. Here we release COD-dipp, a cancer vaccine toolkit as a web-application ( https://www.proteogenomics.ca/COD-dipp ) and open-source high-throughput resource.

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)0.001
metaresearch head score (Gemma)0.001
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 score0.351
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0020.002
Research integrity0.0000.001
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 head0.018
GPT teacher head0.238
Teacher spread0.221 · 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

Citations2
Published2022
Admission routes1
Has abstractyes

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