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Omicron Variant Resources

PHA4GE Bioinformatics Pipelines & Visualization Working Group
Libuit KG, Spinler JK, Southgate J, Black A, Nekrutenko A, Neuhaus B, O’Cathail C, Lemmer D, Jones D, Smith E, Gnimpieba E, Guthrie J, Maturure P, Monsierurs P, Maier W, Langhorst B, Page A, & Niewiadomska AM

Document Changelog
  • 2021-12-19:
    • Added section detailing Omicron lineage and clade nomenclature, COVID-19 scenario modeling resource, and additional reference sequences
    • Updated Pangolin and Nextclade software minimums and resource links for genomic information (e.g. defining mutations), visualizations, and global case counts over time to include B.1.1.529 sub lineages
  • 2022-10-10:
    • Updated variant designations
    • Historical Information / Archived Data added
  • 2023-03-09:
    • Format changelog

Overview

The World Health Organization (WHO) has classified the SARS-CoV-2 B.1.1.529 variant as a Variant of Concern (VOC) under the advice of the Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE)—an independent group of experts that periodically monitors and evaluates the evolution of SARS-CoV-2 and assess if specific mutations and combinations of mutations alter the behavior of the virus. The WHO has assigned the B.1.1.529 VOC the label Omicron per their greek-letter key variant assignment system. The elevation of Omicron to a WHO-designated VOC was based on the TAG-VE's assessment of the variant’s large number of genomic mutations and plausible impact on COVID-19 epidemiology.

The PHA4GE Pipelines and Visualization Working Group has created this document to highlight critical open-source/accesses resources to aid in the understanding and further analysis of the Omicron variant.

In no way does this document represent a comprehensive list of all available SC2 bioinformatics resources. If this document fails to include a valuable public health resource or in some way mischaracterizes a resource mentioned, we encourage community collaboration through pull-requests and/or raised GitHub issues.

Contents

General Information on the Omicron Variant

Below is a list of various educational material, public health announcements and publications, thechnical details and global trackers, phylogenetic visualiations, and resources to assist in data sharing and reporting of the Omicron variant.

Omicron Lineage and Clade Nomenclature

  • The Omicron Variant is the WHO SARS-CoV-2 VOC label for the pango lineage B.1.1.529 (includes BA.1, BA.2, BA.3, BA.4, BA.5 and descendent and recombinant lineage XE) Nextstrain designations include 21K, 21L, 21M, 22A, 22B, and 22C.

Educational Material

Public Health Announcements and Publications

Technical Details and Global Trackers

Phylogenetic Visualizations

Data Reporting and Sharing

  • PHA4GE Resource on Data Sharing: Sharing of sample read and assembly data through internationally accessible databases allows insights to be drawn about how the virus is spreading and mutating across the globe; the more freely available these data are to international researchers and public health scientists, the stronger our decision making can be.
  • PHA4GE Resource on Data Submission: Resources developed to assist in the preparation and submission of raw NGS read data (fastq files), SC2 consensus assemblies (fasta files), and contextual sample metadata to internationally-accessible databases such as NCBI, ENA, and GISAID

Potential Impacts of Spike Protein Mutations

The spike protein of the SARS-CoV-2 Omicron variant contains approximately 32 mutations, many of which have not been observed in previous VOCs. However, based on their location, several of these mutations have the potential to impact immune escape, transmissibility, and detection. Spike mutations found in the Omicron VOC can be analyzed in detail using the Stanford University Coronavirus Antiviral & Resistance Database.

Omicron S-gene mutations

  • Up to 15 mutations have been observed within the receptor binding domain (RBD). The RBD region of the Spike protein interacts directly with the human receptor ACE2 and mutations in this region may have a direct impact on how well SARS-CoV-2 viral particles attach to a host cell.

  • Approximately 8 mutations have been observed within the N-terminal domain (NTD). The NTD of the Spike protein aids in virus attachment and mutations in this region could also impact virus infectivity.

  • Both the RBD and NTD are surface exposed areas of the Spike protein that are targeted by antibodies. Mutations in these regions have the potential to evade immunity by antibodies acquired through previous infection or vaccination.

  • Three mutations occur near the furin cleavage site, the region of the Spike protein responsible for viral-host membrane fusion. Mutations in this region have the potential to affect viral entry into host cells.

Diagnostic and Sequencing Assays

Mutations in the SARS-CoV-2 genome can affect PCR-based diagnostic assays and genomic sequencing. For example, the ThermoFisher TaqPath probe targeting the Spike gene is known to result in S-gene target failure (SGTF) when amplifying nucleic acid preparations from VOC Alpha. This occurs when the SARS-CoV-2 genome contains a deletion resulting in the loss of amino acids 69-70 of the NTD. When coupled with the positive amplification of other SARS-CoV-2 genetic regions, the SGTF has been used as a diagnostic indicator of VOC presence SGF Deletion Assay.

Bioinformatics Resources and Considerations

Genome assembly as well as clade and lineage assignment of Omicron variants should follow the same bioinformatics workflow recommendations outlined in this working group's Bioinformatics Solutions for SARS-CoV-2 Genomic Analysis guidance document. Briefly, raw amplicon read data should be mapped to the Wuhan-1 reference genome and primer trimming performed before a consensus genome is called. Clade annd lineage assignment can then be made by analyzing the resulting consensus genome assemblies with the NextClade and Pangolin software, respectively.

Software Version Minimums

For laboraotires making clade and lineage assignements outside of the NextClade and Pangolin web applications, e.g. through a custom workflow available on CLI, Terra.Bio, or Galaxy Project, please ensure to utilize updated NextClade and Pangolin software capable of making an accurate Omicron clade and lineage designation:

Reference Sequences and Assemblies

SARS-CoV-2 Multiple Sequence Alignments

Primer dropouts in Omicron sequence data may lead to errant evolutionary inferences when performing phylogenetic analysis of SARS-CoV-2 genomes. A proposed work around to these dropout regions is to mask the spike region and adjust the molecular clock rate accordingly, as performed by Trevor Bedford in a recent phylodynamic analysis.

Historical Information / Archived Data