Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames; David Dillon Holcomb; Ofer Kimchi; Michael DiCuccio; Nobuko Hamasaki-Katagiri; Tony Wang; Anton A Komar; Aikaterini Alexaki; Chava Kimchi-Sarfaty

Relative synonymous codon usage (RSCU) and codon pair score (CPS) are commonly used metrics to describe the codon and codon pair usage bias, respectively. RSCU expresses the observed over expected synonymous codon usage ratio, while CPS is the natural log of the observed over expected synonymous codon pair ratio using observed individual codon usage [2, 31] . In our analyses, RSCU and CPS are derived from human genomic codon and codon pair usage frequencies. For ease of comparison, we used ln(RSCU) to measure the codon usage bias. The average CPS across a gene is referred to as codon pair bias (CPB) of the gene [2] . The average ln(RSCU) and CPB of each viral gene was calculated and compared with host genes average ln(RSCU) and CPB ( Figure 5 ). The average RSCU, ln(RSCU) and CPB of each viral gene appear in Table 2 . ORF10 was strikingly the least similar gene to the human genome in terms of both its codon and codon pair usage, followed by the E gene. These genes provide little opportunity for deoptimization, since their sequence is already far from optimal. On the other hand, genes S and N are more similar to human in terms of their codon pair usage. To explore further the potential for codon pair deoptimization, we plotted their CPS across their sequence (Supplemental