RAPID: Subtyping and Identifying Shared Genomic Sequences of SARS-CoV-2 (COVID-19)

人们受到前所未有的大流行的威胁：COVID-19（由SARS-CoV-2引起）。这种病毒现在不仅威胁着身体健康，而且威胁着心理、教育、经济和社会基础设施的每一个角落。到目前为止，没有治疗这种疾病的方法，而疫苗和中和抗体被认为是解决这一危机的最终办法之一。支持疫苗和抗体开发的一项关键知识是了解这种病毒的基因组。全球SARS-CoV-2病毒株共有的共同序列是什么？有哪些亚型？基因组变异是否与疫苗设计的重要基因组区域重叠？利用最先进的机器学习方法，这项研究将确定SARS-CoV-2菌株之间共有的、有代表性的序列，并按主要类型对它们进行分组。该项目将把这些信息与文献中确定的可用于疫苗的重要基因组区域联系起来，从而不断为正在进行的疫苗开发、抗体选择和治疗开发提供信息。这项研究的研究成果将通过每月更新的网络界面为社会带来好处，让疫苗开发人员、生物医学研究界以及普通公众方便地获取上述信息。该项目将支持生物信息学研究生的培训，并为K-12学生和公众提供推广机会。这项工作将是一个持续的努力，每月对SARS-CoV-2亚型进行分类，并更新SARS-CoV-2的共享序列，以促进疫苗开发和抗体设计。具体而言，本研究将侧重于三个目标：1)通过迫使共同序列与所有菌株具有最小的进化距离，或覆盖尽可能多的序列，识别和更新SARS-CoV-2的共同序列；2)将SARS-CoV-2菌株分型为主要组，这对指导治疗、管理和预防措施具有重要意义；3)将SARS-CoV-2亚型和常见基因组序列与文献中鉴定的表位连接起来。为了开发疫苗或中和抗体治疗，至关重要的是要涵盖和考虑主要的变异。算法和可视化工具将在病毒基因组的亚型和共享序列上覆盖经过策划的潜在表位列表，并直接支持疫苗和抗体的开发。该RAPID奖由环境生物学部的系统学和生物多样性科学集群利用《冠状病毒援助、救济和经济安全（CARES）法案》的资金设立。该奖项反映了美国国家科学基金会的法定使命，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。

People are threatened by an unprecedented pandemic: COVID-19 (caused by SARS-CoV-2). This virus is now threatening not only physical health, but also psychology, education, economy, and every corner of the infrastructure of society. So far, there is no treatment for this disease, while vaccines and neutralizing antibodies are perceived as one of the eventual solutions to this crisis. A critical piece of knowledge supporting vaccine and antibody development is understanding the genome of this virus. What is the common sequence shared among the SARS-CoV-2 strains across the globe? What are the subtypes? Are the genome variances overlapping with important genomic regions for vaccine design? Using state of the art machine learning approaches, this research will identify the shared, representative sequence across SARS-CoV-2 strains and group them by major types. This project will connect this information to the important genomic regions identified in the literature that can be used for vaccines, and thereby continuously inform the ongoing effort of vaccine development, antibody selection, and therapeutic development. The research from this study would provide society benefits through monthly updates onto web interfaces that allow the vaccine developers, the biomedical research community as well as the general public to conveniently get access to the above information. This project will support training of a graduate student in bioinformatics and provide outreach opportunities to K-12 students and the public.This work will be a continuous effort to monthly subtype SARS-CoV-2 strains and update the shared sequences of SARS-CoV-2, in order to facilitate vaccine development and antibody design. Specifically, this research will be focusing on three objectives: 1) identifying and updating the common sequences of SARS-CoV-2 by forcing the common sequence to have the minimal evolutionary distance with all strains, or covering as many sequences as possible 2) subtyping the SARS-CoV-2 strains into major groups, which will be important to inform treatment, management and prevention measures; 3) connecting the subtyped and common genomic sequences of SARS-CoV-2 to epitopes identified in the literature. To develop vaccines or neutralizing antibody treatment, it is critical that the major variations are covered and considered. The algorithms and visualization tools will overlay the curated list of potential epitopes on top of the subtypes and the shared sequence of the virus genomes, and directly support the effort of vaccine and antibody development. This RAPID award is made by the Systematics and Biodiversity Science Cluster in the Division of Environmental Biology, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.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.