Single-nucleotide conservation state annotation of SARS-CoV-2 genome

Kwon, Soo Bin; Ernst, Jason

Given the global impact and severity of COVID-19, there is a pressing need for a better understanding of the SARS-CoV-2 genome and mutations. Multi-strain sequence alignments of coronaviruses (CoV) provide important information for interpreting the genome and its variation. We apply a comparative genomics method, ConsHMM, to the multi-strain alignments of CoV to annotate every base of the SARS-CoV-2 genome with conservation states based on sequence alignment patterns among CoV. The learned conservation states show distinct enrichment patterns for genes, protein domains, and other regions of interest. Certain states are strongly enriched or depleted of SARS-CoV-2 mutations, and the state annotations are more predictive than existing genomic annotations in prioritizing bases without nonsingleton mutations, which are likely enriched for important genomic bases. We expect the conservation states to be a resource for interpreting the SARS-CoV-2 genome and mutations.