A Universal Antigen-Ranking Method to Design Personalized Vaccines Targeting Neoantigens against Melanoma

Abstract

Background: The main purpose of this article is to introduce a universal mathematics-aided vaccine design method against malignant melanoma based on neoantigens. The universal method can be adapted to the mutanome of each patient so that a specific candidate vaccine can be tailored for the corresponding patient. Methods: We extracted the 1134 most frequent mutations in melanoma, and we associated each of them to a vector with 10 components estimated with different bioinformatics tools, for which we found an aggregated value according to a set of weights, and then we ordered them in decreasing order of the scores. Results: We prepared a universal table of the most frequent mutations in melanoma ordered in decreasing order of viability to be used as candidate vaccines, so that the selection of a set of appropriate peptides for each particular patient can be easily and quickly implemented according to their specific mutanome and transcription profile. Conclusions: We have shown that the techniques that are commonly used for the design of personalized anti-tumor vaccines against malignant melanoma can be adapted for the design of universal rankings of neoantigens that originate personalized vaccines when the mutanome and transcription profile of specific patients is considered, with the consequent savings in time and money, shortening the design and production time.

Keywords: bioinformatics; combinatorial optimization; immunogenicity; melanoma; personalized medicine; vaccine design.

Figure 1

Sliding window to extract shorter strings. In this figure, we illustrate how our sliding window of length 9 applied to 15 amino acid length peptides gives us the seven sub-peptides. In yellow, the position of the mutated amino acid, which is always preserved inside the sub-peptides.

Figure 2

Violin plots for the value distributions. (a) The distribution of the five main characteristics (immunogenicity, HLA-I binding, HLA-II binding, Gravy index, and VaxiJen score). (b) In this panel, we depict the distribution of the combined score variable. The dots indicate individual values, * is the average value, the central box covers the values from Q3 to Q1, and the horizontal bar indicates the median value.