Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Bioinformatics. 2022 Jul 11;38(14):3549-3556. doi: 10.1093/bioinformatics/btac370.
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. Motivation: 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. Results: Analyzing the mutations from January 2020 to 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 to March 2022.
Our software implementation is available at https://github.com/guangxujin/VOC-alarm.
Supplementary data are available at Bioinformatics online.
突变是引起关注的变异（VOC）克服选择压力的关键，但这一过程仍不清楚。了解突变过程与 VOC 之间的关联是一个未满足的需求。动机：在这里，我们使用约 570 万例 SARS-CoV-2 完整序列的突变，开发了 VOC-alarm 方法来预测 VOC 及其引起的 COVID 浪潮。我们发现，VOC 依赖于突变数量的谱系水平熵值来与其他变体竞争，这表明病毒进化过程中群体水平的突变很重要。因此，我们假设 VOC 是全球范围内突变过程的结果。结果：分析 2020 年 1 月至 2021 年 12 月的突变，我们通过估计进化速度模拟了突变过程，从而将 2020 年 1 月至 2022 年 3 月的时间段分为 8 个阶段。我们通过在阶段 I、III、V 和 VII 中分别估计突变的速度，根据突变熵值预测了 Alpha、Delta、Delta Plus（AY.4.2）和 Omicron（B.1.1.529）。2021 年 11 月下旬，VOC-alarm 警报称，Omicron 与 Delta 和 Delta Plus 竞争强烈，成为一种高传染性变体。使用模拟数据，VOC-alarm 还预测，Omicron 可能导致 2022 年 1 月至 3 月再次出现 COVID 浪潮。可用性和实施：我们的软件实现可在 https://github.com/guangxujin/VOC-alarm 上获得。补充信息：补充数据可在 Bioinformatics 在线获得。
