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

Guerrero Tamayo, AnaSanz Urquijo, BorjaOlivares, IsabelMoragues Tosantos, María DoloresCasado, ConcepciónPastor López, Iker2025-03-062025-03-062024-08Guerrero-Tamayo, A., Sanz Urquijo, B., Olivares, I., Moragues Tosantos, M.-D., Casado, C., & Pastor-López, I. (2024). 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. PLoS ONE, 19(8). https://doi.org/10.1371/JOURNAL.PONE.030939110.1371/JOURNAL.PONE.0309391http://hdl.handle.net/20.500.14454/2463The 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.eng© 2024 Guerrero-Tamayo et al.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 interpretabilityjournal article2025-03-061932-6203