Improved proteasomal cleavage prediction with positive-unlabeled learning

Emilio Dorigatti, Bernd Bischl, Benjamin Schubert

Accurate in silico modeling of the antigen processing pathway is crucial to enable personalized epitope vaccine design for cancer. An important step of such pathway is the degradation of the vaccine into smaller peptides by the proteasome, some of which are going to be presented to T cells by the MHC complex. While predicting MHC-peptide presentation has received a lot of attention recently, proteasomal cleavage prediction remains a relatively unexplored area in light of recent advances in high-throughput mass spectrometry-based MHC ligandomics. Moreover, as such experimental techniques do not allow to identify regions that cannot be cleaved, the latest predictors generate synthetic negative samples and treat them as true negatives when training, even though some of them could actually be positives. In this work, we thus present a new predictor trained with an expanded dataset and the solid theoretical underpinning of positive-unlabeled learning, achieving a new state-of-the-art in proteasomal cleavage prediction. The improved predictive capabilities will in turn enable more precise vaccine development improving the efficacy of epitope-based vaccines. Code and pretrained models are available at https://github.com/SchubertLab/proteasomal-cleavage-puupl.

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