Short communication On the correct interpretation of similarity index in codon usage studies: Comparison with four other metrics and implications for Zika and West Nile virus

Viruses can modify the usage of their synonymous codons to mimic that of their hosts: investigation of codon usage may therefore help increase our understanding of virus biology. The similarity index (SiD or (D(A,B)) is a recent method for estimating the resemblance of the overall codon usage of the hosts to that of a certain virus. Here we report that this index has been systematically misinterpreted in the literature. We first review its mathematical meaning to show that a high value of SiD indicates low codon usage similarity, and not the opposite as frequently reported. We further compared SiD with four other metrics nCAI, nRCDI, ITE and tAI using Zika and West Nile arboviruses in relation to various vectors and hosts. We highlight some differences between the five metrics and present a first bioinformatic evidence that Zika virus is poorly adapted to Culex quinquefasciatus, in accordance with the known biology of this virus. We conclude that SiD, if correctly interpreted, is a useful tool for codon studies, but we advocate that the results from this and other methods are context and time dependent and should be taken with care. A script to automatically calculate SiD from two codon usage tables is available at https://github.com/andrea-silverj/SiDcal.