Pan-cancer analysis of neoepitopes
Abstract
Somatic variations are frequent and important drivers in cancers. Amino acid substitutions can yield neoantigens that are detected by the immune system. Neoantigens can lead to immune response and tumor rejection. Although neoantigen load and occurrence have been widely studied, a detailed pan-cancer analysis of the occurrence and characterization of neoepitopes is missing. We investigated the proteome-wide amino acid substitutions in 8-, 9-, 10-, and 11-mer peptides in 30 cancer types with the NetMHC 4.0 software. 11,316,078 (0.24%) of the predicted 8-, 9-, 10-, and 11-mer peptides were highly likely neoepitope candidates and were derived from 95.44% of human proteins. Binding affinity to MHC molecules is just one of the many epitope features. The most likely epitopes are those which are detected by several MHCs and of several peptide lengths. 9-mer peptides are the most common among the high binding neoantigens. 0.17% of all variants yield more than 100 neoepitopes and are considered as the best candidates for any application. Amino acid distributions indicate that variants at all positions in neoepitopes of any length are, on average, more hydrophobic than the wild-type residues. We characterized properties of neoepitopes in...Continue Reading
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The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts
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