RAPID: Reconstructing the contemporary history and progenitor of SARS-CoV-2 strains causing COVID-19

严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）是COVID-19疾病的根本原因，该疾病已在美国造成多人死亡，并在全球造成数百万人感染。预计它会感染更多的人，并担心造成更高的死亡人数，需要立即进行研究，以了解其基因组生物学和进化。实验室已经快速组装了数万个CoV-2基因组，以表征其变异并跟踪COVID-19的传播。现在需要对这个庞大的数据集进行有意义的分析，以了解过去几个月冠状病毒的变化模式。这些进化模式是做出预测和开发抗击COVID-19产品的关键。进化模式的发现需要明确设计的新方法来利用冠状病毒基因组的显著特征和爆发的历史。该项目将为两名早期职业科学家提供专业发展机会，并将举办一个公共网络研讨会，就如何使用新软件研究病毒进化进行更广泛的教育和培训。将开发推断SARS-CoV-2毒株当代进化史的新分析方法。在初步调查中，新的程序和协议在解决SARS-CoV-2历史中的早期进化事件方面显示出更高的能力。新方法将通过使用经验和计算机模拟数据集进行测试。将对大量收集的冠状病毒株进行分析，以重建其起源和分歧的最早进化事件。实施新方法的新软件将被集成到广泛用于病毒学的分子进化遗传学分析（MEGA）软件中。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the root cause of the COVID-19 disease that has caused many deaths in the US and millions of infections worldwide. It is expected to infect many more and is feared to inflict a higher death toll, requiring immediate research efforts to understand its genome biology and evolution. Experimental laboratories have quickly assembled tens of thousands of CoV-2 genomes to characterize its variation and to track the spread of COVID-19. Now a meaningful analysis of this enormous dataset is needed to understand patterns of coronavirus change over the last few months. These evolutionary patterns are the key to making predictions and developing products to fight COVID-19. The discovery of evolutionary patterns requires new methods explicitly designed to exploit salient features of coronavirus genomes and the history of the outbreaks. This project will provide professional development opportunities for two early career scientists, and a public webinar for broader education and training on how to use the new software to study viral evolution will be hosted.Novel analytical approaches for inferring the contemporary evolutionary history of SARS-CoV-2 strains will be developed. In preliminary investigations, the new procedures and protocols show higher power in resolving early evolutionary events in the SARS-CoV-2 history. New methods will be tested by using empirical and computer-simulated datasets. An extensive collection of coronavirus strains will be analyzed to reconstruct the earliest evolutionary events in its origin and divergence. The new software implementing the new methods will be integrated into the Molecular Evolutionary Genetics Analysis (MEGA) software that is used extensively in virology. This will place sophisticated techniques at the fingertips of scientists via a graphical user interface and command-line versions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.