Genome-wide covariation in SARS-CoV-2
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Updated: Oct 24, 2025

Quantification and Whole Genome Characterization of SARS-CoV-2 RNA in Wastewater and Air Samples
Published on: June 30, 2023
Evan Cresswell-Clay1, Vipul Periwal1
1Laboratory of Biological Modeling, NIDDK, United States of America.
Abstract:
The SARS-CoV-2 virus causing the global pandemic is a coronavirus with a genome of about 30Kbase length. The design of vaccines and choice of therapies depends on the structure and mutational stability of encoded proteins in the open reading frames (ORFs) of this genome. In this study, we computed, using Expectation Reflection, the genome-wide covariation of the SARS-CoV-2 genome based on an alignment of ≈130000 SARS-CoV-2 complete genome sequences obtained from GISAID. We used this covariation to compute the Direct Information between pairs of positions across the whole genome, investigating potentially important relationships within the genome, both within each encoded protein and between encoded proteins. We then computed the covariation within each clade of the virus. The covariation detected recapitulates all clade determinants and each clade exhibits distinct covarying pairs.
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