Neoantigen prediction from genomic and transcriptomic data

Tumor cells acquire distinct genetic characteristics as a means to survive and proliferate indefinitely. Changes in the genetic code can also translate in changes at the protein level, therefore creating a distinguishable signature unique for tumor cells, and absent in normal tissues. The presence of discernable moieties in tumors is particularly attractive because it represents a therapeutic opportunity to target tumor cells with specificity, while sparing non-transformed cells. In this sense neoantigens, short peptides containing a mutated sequence, are seen attractive therapeutic targets because of their confinement within tumor cells. Neoantigens can be recognized with high affinity and specificity by tumor-targeting T cells, which consequently can initiate a potent anti-tumor immune response. While this is feasible and it has been tested in numerous cancer types including melanoma, colon and lung cancer, to mention a few, there are technical challenges in identifying immunogenic neoantigens. In this manuscript we address the topic of neoantigen identification from tumor samples, offering a technical overview of the bioinformatic methods utilized to profile the neoantigenic load of tumor samples obtained from clinical specimens. This is meant to guide readers through the steps of neoantigen identification using genomic data, by suggesting tools and methods that can provide, with a high degree of confidence, reliable results for downstream in vitro and in vivo applications.