Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.

• MeSH
• Bromates toxicity   MeSH
• Humans MeSH
• Chromosome Mapping * instrumentation   methods   MeSH
• Microfluidic Analytical Techniques * instrumentation   methods   MeSH
• Cell Line, Tumor MeSH
• Nanotechnology * instrumentation   methods   MeSH
• DNA Repair genetics   MeSH
• Oxidative Stress drug effects   genetics   MeSH
• DNA Damage * genetics   MeSH
• Gene Expression Regulation MeSH
• Gene Expression Profiling MeSH
• Toxicogenetics * instrumentation   methods   MeSH
• DNA Copy Number Variations MeSH
• Single Molecule Imaging * instrumentation   methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Humans MeSH
• Molecular Epidemiology methods   trends   MeSH
• Mutagenesis physiology   genetics   immunology   MeSH
• Disorders of Environmental Origin diagnosis   epidemiology   etiology   MeSH
• Carcinogenicity Tests methods   trends   utilization   MeSH
• Toxicogenetics methods   organization & administration   trends   MeSH
• Check Tag
• Humans MeSH