Project description:SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. Subgenomic RNA(sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome. Applying our tool(periscope) to ARTIC Network Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA is significantly increased in B.1.1.7(alpha) infections(n=879). This increase is seen over the previous dominant circulating UK lineage, B.1.177(n=943), which is independent of genomic reads, E-gene cycle-threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median sgRNA abundance. We demonstrate that ORF9b protein levels are increased 6-fold in B.1.1.7 compared to a B lineage virus during in vitro culture. We hypothesise that this enhanced presence of ORF9b in B.1.1.7 viruses is a direct consequence of a triple nucleotide mutation in nucleocapsid(28280:GAT>CAT,D3L) creating a transcription regulatory-like sequence complementary to a region 3’ of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles in sequence data to evaluate emerging potential variants of concern.
2021-11-26 | PXD029954 | Pride
Project description:Advancing targeted haplotyping in pharmacogenomics using Oxford Nanopore Technologies' adaptive sampling
