Author: Daniel J Butler; Christopher Mozsary; Cem Meydan; David C Danko; Jonathan Foox; Joel Rosiene; Alon Shaiber; Ebrahim Afshinnekoo; Matthew MacKay; Fritz J Sedlazeck; Nikolay A Ivanov; Maria A Sierra; Diana Pohle; Michael Zeitz; Vijendra Ramlall; Undina Gisladottir; Craig D Westover; Krista Ryon; Benjamin Young; Chandrima Bhattacharya; Phyllis Ruggiero; Bradley W Langhorst; Nathan A Tanner; Justyn Gawrys; Dmitry Meleshko; Dong Xu; Jenny Xiang; Angelika Iftner; Daniela Bezdan; John Sipley; Lin Cong; Arryn Craney; Priya Velu; Ari Melnick; Iman A Hajirasouliha; Thomas Iftner; Mirella Salvatore; Massimo Loda; Lars F Westblade; Shawn Levy; Melissa Cushing; Nicholas P Tatonetti; Marcin Imielinski; Hanna Rennert; Christopher Mason
Title: Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Document date: 2020_4_20
ID: kyoa5gsf_35
Snippet: Total RNA-sequencing data enabled a complete genetic map of the viruses in a significant subset of our samples. Our phylogenetic analysis nominates an A2a subclade (A2a-25563, defined by 25563G>T) which comprises the majority of known NYC samples (including those sequenced outside of this study) (Gonzalez-Reiche et al., 2020) . Though remaining NYC cases show a wide distribution across all identified clades, the predominance (>80% in NYC) of such.....
Document: Total RNA-sequencing data enabled a complete genetic map of the viruses in a significant subset of our samples. Our phylogenetic analysis nominates an A2a subclade (A2a-25563, defined by 25563G>T) which comprises the majority of known NYC samples (including those sequenced outside of this study) (Gonzalez-Reiche et al., 2020) . Though remaining NYC cases show a wide distribution across all identified clades, the predominance (>80% in NYC) of such a narrowly defined set of sequences within NYC from a rare (≤20%) Western European subclade is striking. These results suggest either (1) a very early introduction by a single patient harboring A2a-25563; or (2) multiple A2a-25563 founder events; or (3) disproportionate community transmission of strains within this subclade. The latter possibility could be consistent with A2a-25563 harboring differential fitness with respect to transmissibility or virulence relative to other A2a viruses. Future studies correlating viral genotypes with patient outcomes in larger cohorts will be necessary to determine whether any of these A2a-25563 associated variants, including the 9 bp in-frame deletion in NSP1 (p.141_143KSD), functionally influence viral transmission or disease severity. The polyphyletic pattern of NSP1 p.141_143KSD, comprising both patients within and beyond A2a-25563, including clades outside of A2a, raises the possibility that this variant arose multiple times and may be under positive selection. Given the small number of these variants observed in our analysis (14), larger and more statistically powered datasets will be required to evaluate this hypothesis.
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