VOC-alarm: Mutation-based prediction of SARS-CoV-2 variants of concern.

 : Mutation is the key for a variant of concern (VOC) to overcome selective pressures, but this process is still unclear. Understanding the association of the mutational process with VOCs is an unmet need. Here we developed VOC-alarm, a method to predict VOCs and their caused COVID surges, using mutations of about 5.7 million SARS-CoV-2 complete sequences. We found that VOCs rely on lineage-level entropy value of mutation numbers to compete with other variants, suggestive of the importance of population-level mutations in the virus' evolution. Thus, we hypothesized that VOCs are a result of a mutational process across the globe. Analyzing the mutations from January 2020-December 2021, we simulated the mutational process by estimating the pace of evolution, and thus divided the time period, January 2020-March 2022, into eight stages. We predicted Alpha, Delta, Delta Plus (AY.4.2) and Omicron (B.1.1.529) by their mutational entropy values in the stages I, III, V, and VII with accelerated paces, respectively. In late November 2021, VOC-alarm alerted that Omicron strongly competed with Delta and Delta plus to become a highly transmissible variant. Using simulated data, VOC-alarm also predicted that Omicron could lead to another COVID surge from January 2022-March 2022. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.