Characterizing geographical and temporal dynamics of novel coronavirus SARS-CoV-2 using informative subtype markers

Zhengqiao Zhao; Bahrad A. Sokhansanj; Gail L. Rosen

Moreover, we observe that the diversity of ISMs has increased over time in a manner. We expect this to 491 occur, because as the number of transmissions of the virus between people increases over time, the 492 probability of changes to the sequence that will lead to a different ISM will increase. To evaluate the increase in ISM diversity, we computed the Hamming distance between each of the 50 494 most prevalent ISMs and the ISM of the reference sequence [13] . These distances, although naïve as they are 495 based on an equally probably nucleotide changes, provide a rough measure of how much each ISM has 496 changed relative to the reference. We then plotted the distance of each ISM along the dates of the first 497 sequence in which the ISM was first detected. As Figure 15 illustrates, even though there is significant 498 variability in this rough measure of the difference between ISMs, there is a clearly accelerating trend towards 499 greater differences over time based on the sequence dates. This provides additional confidence in the 500 robustness of subtyping by ISM according to sequence date. By way of further illustrating this point, Figure 501 15 superimposes the cumulative reported number of confirmed COVID-19 cases over time. 6 While these data 502 provide only a limted picture of the actual number of SARS-CoV-2 infections (including because of limited 503 testing), it further demonstrates that ISM subtypes following sequence dates are capable of tracking the 504 actual temporal progress of the virus.