AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies

PLoS One. 2022 Aug 31;17(8):e0273860. doi: 10.1371/journal.pone.0273860. eCollection 2022.

Abstract

Among mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.

MeSH terms

  • Artificial Intelligence
  • COVID-19* / genetics
  • Genome, Viral
  • Humans
  • Machine Learning
  • Mutation*
  • Oligonucleotides* / genetics
  • Phylogeny
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Oligonucleotides
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

T.I. and K.W. received JSPS KAKENHI Grant Number 18K07151. The Japan Society for the Promotion of Science (JSPS) https://www.jsps.go.jp/english/index.html T.A. received JST CREST Grant Number JPMJCR20H1. The Japan Science and Technology Agency (JST) https://www.jst.go.jp/EN/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.