3.3. CoV-2-Cons Variability Analysis by Entropy Scores across the Full Genome
Mismatches between the sequence of in vitro antigen sets and the autologous virus in an infected individual can lead to missed responses. This has been described for highly variable pathogens, such as HCV and HIV, and showed a direct relationship between sequence entropy and the frequency of detected responses [56,57]. Even though the variability of SARS-CoV-2 reported is substantially lower than for HIV and HCV, the sequence entropy was calculated at the amino acid level and as the mean OLP entropy in order to identify positions and OLP that may escape detection in T cell screening assays.
Amino acid positional Shannon entropies were generally highly conserved, although specific more variable positions were identified (Figure S1), linked to specific amino acid variants. The ORF1ab protein, including three of the most variable positions, is shown in Figure 1. In the CoV-2-cons 15–11 OLP set, mean OLP normalized entropies were overall low (Range: 0.947–0.758) and comparable between OLP covering the canonical ORF (Range: 0.947–0.879) and OLP matching the alternative frameshift ORF (Range: 0.932–0.758).