Machine learning models exploring characteristic single-nucleotide signatures in yellow fever virus

PLoS One. 2022 Dec 12;17(12):e0278982. doi: 10.1371/journal.pone.0278982. eCollection 2022.

Abstract

Yellow fever virus (YFV) is the agent of the most severe mosquito-borne disease in the tropics. Recently, Brazil suffered major YFV outbreaks with a high fatality rate affecting areas where the virus has not been reported for decades, consisting of urban areas where a large number of unvaccinated people live. We developed a machine learning framework combining three different algorithms (XGBoost, random forest and regularized logistic regression) to analyze YFV genomic sequences. This method was applied to 56 YFV sequences from human infections and 27 from non-human primate (NHPs) infections to investigate the presence of genetic signatures possibly related to disease severity (in human related sequences) and differences in PCR cycle threshold (Ct) values (in NHP related sequences). Our analyses reveal four non-synonymous single nucleotide variations (SNVs) on sequences from human infections, in proteins NS3 (E614D), NS4a (I69V), NS5 (R727G, V643A) and six non-synonymous SNVs on NHP sequences, in proteins E (L385F), NS1 (A171V), NS3 (I184V) and NS5 (N11S, I374V, E641D). We performed comparative protein structural analysis on these SNVs, describing possible impacts on protein function. Despite the fact that the dataset is limited in size and that this study does not consider virus-host interactions, our work highlights the use of machine learning as a versatile and fast initial approach to genomic data exploration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brazil / epidemiology
  • Humans
  • Machine Learning
  • Nucleotides
  • Primates
  • Yellow Fever* / epidemiology
  • Yellow fever virus* / genetics

Substances

  • Nucleotides

Grants and funding

A.S. was supported by Decit, SCTIE, Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Científico - CNPq - (Grants 440685/2016-8 and 440856/2016-7) https://www.gov.br/cnpq/pt-br; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Grants 88887.130716/2016-00, 88881.130825/2016-00 and 88887.130823/2016-00) https://www.gov.br/capes/pt-br; The European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement No. 734548 - https://zikalliance.tghn.org. All other authors received no specific funding for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.