RAPID: finding virulence genes as therapeutic targets in Covid-19

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This RAPID award is made by the Division of Biological Infrastructure (DBI) using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act. This award to the University of Georgia will leverage bioinformatics tools to identify virulence genes that assisted SARS-COV-2 in jumping species boundaries. Identifying shared genetic changes between human SARS-COV-2 and its relatives in mammalian reservoirs in the bat, pangolin, and civit is important to understanding the virus mode of action. It is especially critical to identify which of the changes contribute to human virulence of SARS-COV-2. The researchers will analyze 3200+ genomes from SARS-COV-2 and coronavirus genomes from animal reservoirs to look at genetic changes associated with virulence and COVID-19 symptoms. To accomplish this work, new software tools will be developed to better leverage modern computer graphics processing units (GPUs) for high-speed parallel computing. The project will engage graduate students and REU participants in interdisciplinary research of critical national importance and contribute useful tools for future bioinformatic research.The objective of this project is to identify virulence genes that enable SARS-COV-2 to jump species boundaries from vertebrate reservoirs. The project has three main components: (1) building gene trees within species trees of coronavirus by coalescent methods; (2) testing for shared polymorphisms under selective sweep between natural reservoirs and human SARS-COV-2; (3) validating candidates identified in task (2) independently by comparing gene genealogies for selective sweep (under selection for virulence) vs. incomplete lineage sorting. An interdisciplinary team from genetics, bioinformatics, and infectious diseases will develop gene trees within a species tree of 3,200+ published SARS-COV-2 genomes using a novel BEST coalescent method developed for GPUs. Results from these studies will be rapidly disseminated and published in peer-reviewed journals, presented at scientific conferences, and made available through shared software repositories.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.