Identification of CD8 + T cell epitopes through proteasome cleavage site predictions
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METHODOLOGY
Identification of CD8+ T cell epitopes through proteasome cleavage site predictions Marta Gomez‑Perosanz†, Alvaro Ras‑Carmona†, Esther M. Lafuente and Pedro A. Reche*
From 3rd International Workshop on Computational Methods for the Immune System Function (CM‑ ISF 2019) San Diego, CA, USA. 18-21 November 2019 *Correspondence: [email protected] † Marta Gomez-Perosanz and Alvaro Ras-Carmona have contributed equally Laboratory of Immunomedicine, Department of Immunology, Faculty of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, s/n, 28040 Madrid, Spain
Abstract Background: We previously introduced PCPS (Proteasome Cleavage Prediction Server), a web-based tool to predict proteasome cleavage sites using n-grams. Here, we evaluated the ability of PCPS immunoproteasome cleavage model to discriminate CD8+ T cell epitopes. Results: We first assembled an epitope dataset consisting of 844 unique virus-specific CD8+ T cell epitopes and their source proteins. We then analyzed cleavage predictions by PCPS immunoproteasome cleavage model on this dataset and compared them with those provided by a related method implemented by NetChop web server. PCPS was clearly superior to NetChop in term of sensitivity (0.89 vs. 0.79) but somewhat inferior with regard to specificity (0.55 vs. 0.60). Judging by the Mathew’s Correlation Coefficient, PCPS predictions were overall superior to those provided by NetChop (0.46 vs. 0.39). We next analyzed the power of C-terminal cleavage predictions provided by the same PCPS model to discriminate CD8+ T cell epitopes, finding that they could be discriminated from random peptides with an accuracy of 0.74. Following these results, we tuned the PCPS web server to predict CD8+ T cell epitopes and predicted the entire SARS-CoV-2 epitope space. Conclusions: We report an improved version of PCPS named iPCPS for predicting proteasome cleavage sites and peptides with CD8+ T cell epitope features. iPCPS is available for free public use at https://imed.med.ucm.es/Tools/pcps/. Keywords: Proteasome, Immunoproteasome, Prediction, Peptide, CD8+ T cell epitope, SARS-CoV-2
Background Proteasomes are multicatalytic protease complexes that play a central role in cellular protein homeostasis by degrading damaged and misfolded proteins [1–3]. Within the cell, the majority of proteins destined to degradation are marked with ubiquitin and delivered to the proteasome, which cut them into peptide fragments that are then easily degraded by other proteases up to recoverably amino acids [4]. Proteasomes can also © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Cre
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