ArticleProceedings of the National Academy of Sciences of the United States of America2024
Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 16 citations in OpenAlex.
- Highly biased DNA sequence reconstruction in DNA storage with multi-scale attention mechanism and contrast learning.Synthetic and systems biotechnology · 2026Article
- Shared quasispecies architecture in experimental and natural RNA virus populations.Virus evolution · 2026Article
- Methods to Characterize Mutant Spectra of RNA Viruses: The Case of SARS-CoV-2.Methods in molecular biology (Clifton, N.J.) · 2026Article
- SARS-CoV-2 mutant spectrum complexity is an epidemiologically evolvable trait.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SARS-CoV-2 biological clones are genetically heterogeneous and include clade-discordant residues.Journal of virology · 2025Article
- A general and biomedical perspective of viral quasispecies.RNA (New York, N.Y.) · 2025Review
- Quasispecies theory and emerging viruses: challenges and applications.Npj viruses · 2024Review
- Point mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection.Genome medicine · 2024Article
- SARS-CoV-2: pathogenesis, therapeutics, variants, and vaccines.Frontiers in microbiology · 2024Review
- SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?Frontiers in microbiology · 2024Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.
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