Abstract
AbstractImmunopeptidomics is crucial for immunotherapy and vaccine development. Because the generation of immunopeptides from their parent proteins does not adhere to clear-cut rules, rather than being able to use known digestion patterns, every possible protein subsequence within human leukocyte antigen (HLA) class-specific length restrictions needs to be considered during sequence database searching. This leads to an inflation of the search space and results in lower spectrum annotation rates. Peptide-spectrum match (PSM) rescoring is a powerful enhancement of standard searching that boosts the spectrum annotation performance. We analyze 302,105 unique synthesized non-tryptic peptides from the ProteomeTools project on a timsTOF-Pro to generate a ground-truth dataset containing 93,227 MS/MS spectra of 74,847 unique peptides, that is used to fine-tune the deep learning-based fragment ion intensity prediction model Prosit. We demonstrate up to 3-fold improvement in the identification of immunopeptides, as well as increased detection of immunopeptides from low input samples.
Funder
Fonds Wetenschappelijk Onderzoek
Publisher
Springer Science and Business Media LLC
Cited by
3 articles.
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