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Prediction of proteasomal cleavage sites using PCPS

机译：使用PCPS预测蛋白酶体切割位点

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The proteasome complex is the main responsible of proteolytic degradation of cytosolic proteins, generating the C-terminus of MHC I-restricted peptide ligands and CD8 T cell epitopes. Prediction of proteasomal cleavage sites is thus relevant for predicting CD8 T cell epitopes. We previously reported an n-gram based method to predict proteasomal cleavage sites named PCPS, which is implemented for free public use online at http://imed.med.ucm.es/pcps/. Here, we used a set of 59 Hepatitis C Virus (HCV) CD8 T-cell epitopes to analyze cleavage predictions by PCPS and compared them with those provided by a related method implemented in NetChop web server. PCPS clearly outperformed NetChop in sensitivity (0.88 and 0.78, respectively); it identified much better than NetChop that the C-terminus of tested CD8 T cell epitopes likely resulted from proteasomal cleavage. However, PCPS identified additional preferential cleavage sites within the tested epitopes more often than NetChop, which resulted in lower specificity (0.57 vs 0.66, respectively). Proteasomal cleavage site predictions are used to enhance CD8 T cell epitopes by discarding peptides resulting from peptide-MHC I binding models that do not have a C-terminus compatible with proteasome production. Thereby, we have now implemented proteasomal cleavage site predictions provided by PCPS n-grams in RANKPEP, a tool to identify peptides presented by MHC molecules, allowing to filter out peptides predicted to bind to MHC I molecules that are unlikely to result from proteasomal cleavage. RANKPEP is available for free public use online at http://imed.med.ucm.es/Tools/rankpep_new.html.
机译：蛋白酶体复合物是胞浆蛋白水解降解，产生MHC I限制性肽配体和CD8 T细胞表位的C端的主要负责人。因此，蛋白酶体切割位点的预测与预测CD8 T细胞表位有关。我们之前曾报道过一种基于n-gram的方法来预测名为PCPS的蛋白酶体切割位点，该方法可在http://imed.med.ucm.es/pcps/在线免费实现。在这里，我们使用了一组59种丙型肝炎病毒（HCV）CD8 T细胞表位来分析PCPS的切割预测，并将其与NetChop Web服务器中实现的相关方法所提供的切割预测进行比较。 PCPS的灵敏度明显优于NetChop（分别为0.88和0.78）;它比NetChop更好地表明，被测试的CD8 T细胞表位的C端可能是由蛋白酶体切割引起的。但是，与NetChop相比，PCPS在被测表位中发现更多的优先切割位点的可能性更高，导致特异性降低（分别为0.57和0.66）。蛋白酶体切割位点预测用于通过丢弃不具有与蛋白酶体生产相容的C末端的肽-MHC I结合模型产生的肽来增强CD8 T细胞表位。因此，我们现在已经在RANKPEP中实现了PCPS n-gram提供的蛋白酶体切割位点预测，RANKPEP是一种识别由MHC分子呈递的肽的工具，允许滤除预计与蛋白酶体切割不大可能结合的MHC I分子结合的肽。 RANKPEP可在http://imed.med.ucm.es/Tools/rankpep_new.html上免费在线免费使用。

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