Colorectal cancer vaccines: in silico identification of tumor-specific antigens associated with frequent HLA-I alleles in the costa rican Central Valley population

Abstract

Colorectal cancer is a complex disease in which uncontrolled growth of abnormal cells occurs in the large intestine (colon or rectum). The study of tumor-specific antigens (neoantigens), molecules that interact with the immune system, has been extensively explored as a possible therapy called in silico cancer vaccine. Cancer vaccine studies have been triggered by the current high-throughput DNA sequencing technologies. However, there is no universal bioinformatic protocol to study tumor-antigens with DNA sequencing data. We propose a bioinformatic protocol to detect tumor-specific antigens associated with single nucleotide variants (SNVs) or “mutations” in colorectal cancer and their interaction with frequent HLA alleles (complex that present antigens to immune cells) in the Costa Rican Central Valley population. We used public data of human exome (DNA regions that produce functional products, including proteins). A variant calling analysis was implemented to detect tumorspecific SNVs, in comparison to healthy tissue. We then predicted and analyzed the peptides (protein fragments, the tumor specific antigens) derived from these variants, in the context of its affinity with frequent alleles of HLA type I of the Costa Rican population. We found 28 non-silent SNVs, present in 26 genes. The protocol yielded 23 strong binders peptides derived from the SNVs for frequent alleles (greater than 8%) for the Costa Rican population at the HLA-A, B and C loci. It is concluded that the standardized protocol was able to identify neoantigens and this can be considered a first step for the eventual design of a colorectal cancer vaccine for Costa Rican patients. To our knowledge, this is the first study of an in silico cancer vaccine using DNA sequencing data in the context of the Costa Rican HLA alleles.