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HLApollo: Towards designing improved cancer immunotherapy targets with a superior peptide-MHC-I presentation model

Authors: William John Thrift; Nicolas W. Lounsbury; Quade Broadwell; Amy Heidersbach; Emily Freund; Yassan Abdolazimi; Qui T Phung; +11 Authors

HLApollo: Towards designing improved cancer immunotherapy targets with a superior peptide-MHC-I presentation model

Abstract

Based on the success of cancer immunotherapy, personalized cancer vaccines have recently emerged as the vanguard of oncology treatment. Because antigen presentation on MHC class I (MHC-I) is key to the adaptive immune response to cancerous cells, it is critical to have highly predictive computational methods to model which peptides are presented on MHC-I. Here, we introduce HLApollo, a transformer-based model with end-to-end treatment of MHC-I sequence, deconvolution of multi-allelic data, and ligand-flanking sequences. We develop negative-set switching, a novel training strategy that greatly reduces overfitting, which is key to HLApollo’s performance, leading to increases of 20.19% and 4.1% in average precision (AP) vs. next best model on MHC-I presentation and immunogenicity, respectively. Incorporating protein features derived from protein language models yielded further gains and reduced the need for gene expression measurements. We achieve excellent pan-allelic generalization, and create a framework for estimating performance on untrained alleles. This guides the clinical use of HLApollo, where rare alleles may be observed – particularly for individuals from underrepresented ancestries. Our work uses all facets of available MHC-I data to develop a highly accurate MHC-I presentation predictor that meaningfully improves immunogenicity prediction and allelic coverage, important for clinical applications of personalized neoantigen vaccines.

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Keywords

neoepitope, ligandome, neoantigen, ligand presentation, peptide presentation, benchmark, HLApollo, MHC-I, transformer, cancer, immunotherapy, MHC, personalized cancer vaccine

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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Cancer Research