Statistical Analysis and Tokenization of Epitopes to Construct Artificial Neoepitope Libraries

Abstract

Epitopes are specific regions on an antigen's surface that the immune system recognizes. Epitopes are usually protein regions on foreign immunestimulating entities such as viruses and bacteria, and in some cases, endogenous proteins may act as antigens. Identifying epitopes is crucial for accelerating the development of vaccines and immunotherapies. However, mapping epitopes in pathogen proteomes is challenging using conventional methods. Screening artificial neoepitope libraries against antibodies can overcome this issue. Here, we applied conventional sequence analysis and methods inspired in natural language processing to reveal specific sequence patterns in the linear epitopes deposited in the Immune Epitope Database (www.iedb.org) that can serve as building blocks for the design of universal epitope libraries. Our results reveal that amino acid frequency in annotated linear epitopes differs from that in the human proteome. Aromatic residues are overrepresented, while the presence of cysteines is practically null in epitopes. Byte pair encoding tokenization shows high frequencies of tryptophan in tokens of 5, 6, and 7 amino acids, corroborating the findings of the conventional sequence analysis. These results can be applied to reduce the diversity of linear epitope libraries by orders of magnitude.

In silico designed novel multi-epitope mRNA vaccines against Brucella by targeting extracellular protein BtuB and LptD

“…Epitopes refer to specific regions on the surface of antigens that are identified by the immune system 50 . In this study, the conserved region of the chosen protein was retrieved from the National Center for Biotechnology Information (NCBI) 51 (https:// www.ncbi.nlm.nih.gov/accessed ) and were (1) LPS assembly protein LptD (accession number WP_011068938.1) lptD, (2)TonB-dependent receptor Outer membrane BTuB(accession number WP_004691650.1 )1), which were identified as potential protective antigens 19 .…”