MutAIverse: an AI-powered, mechanism-backed platform for discovering novel DNA adducts and their precursor genotoxins.

Genotoxin exposure leads to DNA adduct formation, potentially causing mutations if unrepaired. Current DNA adductomics platforms or analytical workflows are limited by incomplete spectral libraries, reliance on experimentally validated adducts, limited cellular contexts, and inefficient computational methodologies. We introduce MutAIverse, an advanced AI-driven DNA adductomics analysis platform that overcomes these limitations by leveraging intracellular mechanistic modeling of genotoxin bioactivation to construct a comprehensive DNA adduct library and offers advanced spectral mapping. MutAIverse integrates experimentally validated and chemically valid putative DNA adducts, enabling interpretable retrograde tracking to parental genotoxins. Validation of MutAIverse against experimental MS/MS datasets demonstrated the detection of both known and novel adducts. Furthermore, application to in-house generated DNA adductomics data from tissue biopsies of smokeless tobacco-induced head and neck cancer patients revealed selective enrichment of both novel and known DNA adducts; a subset of them was validated using MS/MS analysis. Collectively, MutAIverse provides a robust, end-to-end, and interpretable platform for advanced DNA adductomics analysis.Scientific ContributionThis study introduces MutAIverse, a generative AI‑powered platform that constructs a comprehensive, mechanism‑backed DNA adduct library from genotoxin metabolism simulations, enables interpretable retrograde tracing to parental genotoxins, and provides an end‑to‑end analytical workflow. By outperforming existing spectral libraries in coverage and experimental validation across multiple datasets, MutAIverse offers a robust tool for advancing DNA adductomics in toxicology and cancer research.