Simulation of Silent and Non-Silent Mutagenesis in TP53 by Nucleoside Analogues: A Computational Insight Enhanced by COSMIC Integration
Abstract
Chur Chin
Nucleoside analogues are widely applied in antiviral and chemotherapeutic contexts, yet their subtle mutagenic impact on host genomes is insufficiently modeled. This study simulates analogue-induced point mutations across a 300 bp exon segment of the TP53 gene. Probabilistic misincorporation of entecavir, lamivudine, and azacytidine was analyzed in terms of silent, missense, and nonsense mutation profiles. Simulation results were overlaid with COSMIC TP53 data to assess realism. While silent mutations dominated in silico, missense mutations in real-world cancer samples, particularly at hotspot CpG codons, were far more common. Our findings support computational mutagenesis as a valuable screening tool for genomic safety profiling of therapeutic analogues.
