Precise score for the prediction of peptides cleaved by the proteasome

Motivation: An 810mer can become a cytotoxic T lymphocyte epitope only if it is cleaved by the proteasome, transported by TAP and presented by MHC-I molecules. Thus most of the epitopes presented to cytotoxic T cells in the context of MHC-I molecules are products of intracellular proteasomal cleavage. These products are not random, as peptide production is a function of the precise sequence of the proteins processed by the proteasome. Results: We have developed a score for the probability that a given peptide results from proteasomal cleavage. High scoring peptides are those that are cleaved in their extremities and not in their center, while low scoring peptides are either cleaved in their centers or not cleaved in their extremities. The current work differs from most previous works, in that it determines the production probability of an entire peptide, rather than trying to predict specific cleavage sites. We further present different score functions for the constitutive and the immunoproteasome. Our results were validated to have low error levels against multiple epitope databases. We provide here a novel computational tool and a website to use it-http://peptibase.cs.biu.ac.il/PepCleave_II/ to assess the probability that a given peptide indeed results from proteasomal cleavage.