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

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.

Recombination in Coronaviruses, with a Focus on SARS-CoV-2

“…As soon as the possibility of recombination emerged, nomenclature systems started considering how to name these sublineages. In the PANGOLIN phylogeny, all top-level lineages that are recombinants have a prefix that begins with "X" [73]. In most cases, they expect a minimum of 50 sequences to design a novel recombinant linage, but exceptions arise if the recombinant has a particular novelty or significance, with unusual breakpoint and/or parental lineages.…”

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

“…The phylogenetic classification is widely used as a fundamental method for emergent SARS-CoV-2 strain classification in the clade-nomenclature system (terming the major strain as clade code such as GR) by Global Initiative of Sharing All Influenza Data (GISAID) 28 or NextStrain 29 or Pango lineage system (terming the major strain as letter and number with point interval such as B.1.1.7) by Pango Network 30 (Fig. 1a ).…”

Comparative analysis of SARS-CoV-2 quasispecies in the upper and lower respiratory tract shows an ongoing evolution in the spike cleavage site

“…Haplotype sequences for each sample were obtained from the alignment SAM files, using the software CliqueSNV ( Knyazev et al, 2018 ). The hedgehog algorithm was used on the most abundant haplotype of each sample to classify the SARS-CoV-2 strains using only the S protein sequences ( O'Toole et al, 2022 ). In parallel, alignment data was processed with samtools ( Li et al, 2009 ) and bam-readcount ( https://github.com/genome/bam-readcount ) in order to calculate the number of occurrences of each nucleotide and indel in all positions of the reference.…”