Study: Rapid threat detection in SARS-CoV-2. Image Credit: SWKStock/Shutterstock

Scientists present novel high-precision framework for SARS-CoV-2 genomic surveillance

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In a recent study published in the medRxiv*preprint server, researchers presented a novel framework for genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on case studies from New York (NY), the United States (USA) and the United Kingdom (UK).

Study: Rapid detection of threats in SARS-CoV-2. Image Credit: SWKStock/Shutterstock

SARS-CoV-2 has exhibited significantly increased transmissibility due to the continued evolution of the SARS-CoV-2 spike (S) protein that mediates binding interactions between SARS-CoV-2 S and hACE2 (converting enzyme). of human angiotensin 2) and, therefore, the efficiency of host invasion by SARS-CoV-2. SARS-CoV-2 S mutations not only affect viral transmission, but also increase the chances of reinfections, raising concerns regarding the efficacy of vaccines against coronavirus disease 2019 (COVID-19).

About the study

In the current study, researchers developed a SARS-CoV-2 genomic surveillance framework based on case studies from New York, the UK, and the US and data obtained from the Global Initiative to Share All database. influenza data (GISAID).

The framework relied on coevolutionary genomic sites as building blocks rather than genomic sequences and considered relationships between multiple sequence alignment (MSA) columns in which each column represented a locus or genetic site. MSA was considered to be irreducible and to exhibit a motif complex representative of coevolutionary relationships between different genomic sites, such that if multiple sites were linked, concomitant mutations would occur at all sites; however, the link would be preserved.

The link between the motif-based variant (M) of Omicron (OmicronMETER) with BA.1METER mutations and variant based on Omicron phylogeny (P) (OmicronP) with BA.1P Mutations in SARS-CoV-2 S were tested when the framework triggered an alert (in the first week of December 2021). Additionally, sitelinks in DeltaMETERBA.2METERBA.4METER and BA.5METER when their corresponding reason-based alerts were evaluated.

Complex motif differentials (D) were analyzed to improve understanding of the relational structures of MSA evolution. Alerts were issued only for suitably large D values ​​and the presence of critical clusters (persistent clusters with entropy increases > 0.35), and a variant was considered a key variant if it constituted > 50% of the population in a determinated place .

The surveillance framework was applied prospectively and retrospectively. The retrospective analysis was based on SARS-CoV-2 sequence data obtained from the UK (during the emergence of the Delta and Alpha variants) and the US (during the emergence of the Omicron and Omicron BA.2 variants). For the analysis, the prevalence of SARS-CoV-2 was known and threats could be mapped.

For prospective analysis, New York data on the occurrence of Omicron BA.2.12/Omicron BA.2.12.1 and Omicron BA.4/BA.5 were analyzed, and not all SARS-CoV-threats could be mapped. 2 and, therefore, is considered unknown. Surveillance was validated by testing SARS-CoV-2 populations at various temporal and spatial scales: city, state, country, and three-day, weekly, and monthly.


The framework issued alerts based on GISAID data and reasons on May 16, 2022 in relation to a group of co-evolving sites comprising several genomic sites (n = 7) that were assigned to Omicron BA.5, of which, one site encoded the D3N mutation in the SARS-CoV-2 membrane protein (M), three sites encoded the ORF6:D61L mutation, and three sites encoded the A27259C, C27889T, and C26858T mutations.

When a new perspective was gained and projected as sequences, the cluster separated into two mutually exclusive blocks (nuc:C27889T, m:D3N) comprising co-evolutionary regions linked to reverse amino acid substitutions such as ORF6:D61L,nuc:A27259C, core :C26858T. The framework issued timely alerts based on the appearance and disappearance of SARS-CoV-2 variants with accuracies of 99%, 89%, and 100% for the New York, UK, and US case studies, respectively, and >85% Overall Accuracy.

In case studies, the team found that coevolutionary sites contained in critical clusters almost always exhibited reverse mutations or exclusive mutations. omicronMETER represented a unique critical group of 55 coevolutionary sites exhibiting OmicronP mutations (n=30), BA.1P mutations (n=13), and DeltaP (n=13) reverse mutations. The cluster expanded in the following week to contain 68 coevolutionary sites comprising all sites that exhibited BA.1P mutations

SARS-CoV-2 variants that triggered alerts exhibited linked reverse mutations in their underlying critical groups, except BA.2.12. Furthermore, BA.5 did not differ from BA.4 in SARS-CoV-2 S mutations, although BA.5 exhibited a critical cluster independently of any SARS-CoV-2 S mutation and involved a distinct SARS M mutation. -CoV-2. The alerts issued by the surveillance system were specific but consistent across multiple geographic regions and were robust for multiple parameter options.

Overall, the study findings highlighted the accuracy of the new framework for SARS-CoV-2 surveillance in issuing real-time, reason-based alerts on the appearance and disappearance of key SARS-CoV-2 variants. The critical clusters that triggered the alerts were able to detect variant mutations, and the variants were characterized by linking mutations that deviated from the wild-type (WT) SARS-CoV-2 strain and reverse mutations.

*Important news

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.

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