Examinando por Autor "Guerrero Tamayo, Ana"

Mostrando 1 - 2 de 2
  • Miniatura
    Ítem
    Classification of SARS-CoV-2 sequences as recombinants via a pre-trained CNN and identification of a mathematical signature relative to recombinant feature at Spike, via interpretability
    (Public Library of Science, 2024-08) Guerrero Tamayo, Ana; Sanz Urquijo, Borja; Olivares, Isabel; Moragues Tosantos, María Dolores; Casado, Concepción; Pastor López, Iker
    The global impact of the SARS-CoV-2 pandemic has underscored the need for a deeper understanding of viral evolution to anticipate new viruses or variants. Genetic recombination is a fundamental mechanism in viral evolution, yet it remains poorly understood. In this study, we conducted a comprehensive research on the genetic regions associated with genetic recombination features in SARS-CoV-2. With this aim, we implemented a two-phase transfer learning approach using genomic spectrograms of complete SARS-CoV-2 sequences. In the first phase, we utilized a pre-trained VGG-16 model with genomic spectrograms of HIV-1, and in the second phase, we applied HIV-1 VGG-16 model to SARS-CoV-2 spectrograms. The identification of key recombination hot zones was achieved using the Grad-CAM interpretability tool, and the results were analyzed by mathematical and image processing techniques. Our findings unequivocally identify the SARS-CoV-2 Spike protein (S protein) as the pivotal region in the genetic recombination feature. For non-recombinant sequences, the relevant frequencies clustered around 1/6 and 1/12. In recombinant sequences, the sharp prominence of the main hot zone in the Spike protein prominently indicated a frequency of 1/ 6. These findings suggest that in the arithmetic series, every 6 nucleotides (two triplets) in S may encode crucial information, potentially concealing essential details about viral characteristics, in this case, recombinant feature of a SARS-CoV-2 genetic sequence. This insight further underscores the potential presence of multifaceted information within the genome, including mathematical signatures that define an organism’s unique attributes.
  • Miniatura
    Ítem
    Mathematical patterns associated with genetic recombination in HIV-1 and SARS-CoV-2 via explainability in CNNs: relationship of interpretability scoremaps with viral phylogeny and the role of the third codon nucleotide
    (Universidad de Deusto, 2025-01-10) Guerrero Tamayo, Ana; Moragues Tosantos, María Dolores; Pastor López, Iker; Facultad de Ingeniería
    To research genetic recombination among viruses, we applied genomic spectrograms and pre-trained CNNs via Transfer Learning, followed by explainability tools. Our approach aimed to understand recombination mechanisms and characterize genomic sequences. Via this methodology, we detected mathematical patterns that indicated genetic recombination in complete HIV-1 sequences. The main hot zone was near f = 1/3 in 5'LTR, extending to the first half of gag. LTRs regulate gene expression and virus replication. Nucleotides A and T in polyA and polyT stretches make these regions prone to polymerase skipping, aiding genetic recombination. The high Adenine content in HIV-1 explains the prominent role of A and, secondly, T. We found a high correlation between hot zone similarity and phylogenetic proximity, with subtypes U, G, and O showing unique patterns. The CNN's behavior aligned with the biological traits of these subtypes. Our phylogenetic analysis and literature review confirmed the microbiological reality for subtype U. For subtype G, our results supported its potential recombinant origin and provided data for future research. Applying Two-Stage Transfer Learning and Three-Step Explainability to complete SARS-CoV-2 genomic spectrograms, we detected a clear mathematical signature associated with the recombinant feature at f = 1/6 in the Spike protein, which is crucial for SARS-CoV-2 evolution and with multiple double-crossover genetic recombination events. By this methodology, we also identified clear mathematical signatures for non-recombinant SARS-CoV-2 variants: pre-VOC, Alpha, Delta, and Omicron. Analyzing recombinant and non-recombinant SARS-CoV-2 sequences, we found a high Thymine content exceeding 45% in the third codon nucleotides at Spike protein. This phenomenon is statistically significant considering the low conservation degree of nucleotides in Spike (0.23%). We found evidence suggesting that third codon nucleotides, less significant for amino acid coding, may contain additional information characterizing SARS-CoV-2. Periodicities of 3 and their multiples were linked to recombinant features in HIV-1 and SARS-CoV-2, and to specific variants in SARS-CoV-2. This suggests that third-position nucleotides may hold encrypted information affecting viral classification. Validating this hypothesis could reshape our understanding of the genetic code and spur new research in molecular biology and viral evolution.