Pango lineage designation and assignment using SARS-CoV-2 spike gene nucleotide sequences

BMC Genomics. 2022 Feb 11;23(1):121. doi: 10.1186/s12864-022-08358-2.

Abstract

Background: More than 2 million SARS-CoV-2 genome sequences have been generated and shared since the start of the COVID-19 pandemic and constitute a vital information source that informs outbreak control, disease surveillance, and public health policy. The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. It is therefore important to understand how much information about Pango lineage status is contained in spike-only nucleotide sequences. Here we explore how Pango lineages might be reliably designated and assigned to spike-only nucleotide sequences. We survey the genetic diversity of such sequences, and investigate the information they contain about Pango lineage status.

Results: Although many lineages, including the main variants of concern, can be identified clearly using spike-only sequences, some spike-only sequences are shared among tens or hundreds of Pango lineages. To facilitate the classification of SARS-CoV-2 lineages using subgenomic sequences we introduce the notion of designating such sequences to a "lineage set", which represents the range of Pango lineages that are consistent with the observed mutations in a given spike sequence.

Conclusions: We find that many lineages, including the main variants-of-concern, can be reliably identified by spike alone and we define lineage-sets to represent the lineage precision that can be achieved using spike-only nucleotide sequences. These data provide a foundation for the development of software tools that can assign newly-generated spike nucleotide sequences to Pango lineage sets.

Keywords: Genomic surveillance; Lineage; Pango; SARS-CoV-2; Spike.

MeSH terms

  • Base Sequence
  • COVID-19*
  • Humans
  • Mutation
  • Pandemics
  • Phylogeny
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Spike Glycoprotein, Coronavirus