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oai:figshare.com:article/34036611 2026-09-30T18:17:29Z category_1 category_4 category_12 category_14 category_873 category_64 portal_63 item_type_6 month_year_09_2026

Nanopore Sequencing Identification of DNA Aristolochic Acid Adducts Ran Liu (303585) Yezhuang Shen (25145556) Jie Mao (1630690) Chunzheng Li (4114201) Yawei Zhang (114654) Mandong Hu (5922461) Yizhe Zhang (425334) Qiuying Han (12864893) Weili Gong (4803642) Liang Chen (73736) Kun He (178646) Tao Zhou (117050) Weihua Li (144468) Xianxing Xie (25145559) Biophysics Biochemistry Cell Biology Molecular Biology Chemical Sciences not elsewhere classified Cancer provides highly sensitive multidimensional signature associated increased odds ratios including elevated error normalized signal levels enzymatically digested dna derived dna adducts associated signal characteristics based analytical approach calling quality scores nanopore sequencing identification lc – ms adduct induces consistent intrinsic signal deviations specifically incorporated al defined sequence context explored nanopore sequencing nanopore sequencing investigating dna new approach defined sites calling outcomes calling features da incorporated study supports retain positional novel strategy localized alterations dwell time driving carcinogenesis commonly relies characteristic deviations adduct presence adduct directly Aristolochic acid (AA) is a Group I carcinogen that forms covalent DNA adducts following metabolic activation, inducing characteristic mutational signatures and driving carcinogenesis. Liquid chromatography–mass spectrometry (LC–MS/MS) provides highly sensitive and specific detection of AA-derived DNA adducts, but commonly relies on enzymatically digested DNA, which does not retain positional and sequence-context information along individual DNA molecules. Here, we explored nanopore sequencing as a novel strategy for characterizing aristolactam II–deoxyadenosine DNA adducts (AL-II-dA) in a defined synthetic DNA context via the detection of intrinsic signal deviations. Using chemically synthesized AL-II-dA incorporated at defined sites, we show that the adduct induces consistent and localized alterations in normalized signal levels and dwell time across two independent sequencing platforms. These deviations were accompanied by changes in base-calling outcomes, including elevated error-specific base (ESB) values, increased odds ratios, and reduced base-calling quality scores (Q-scores), collectively forming a multidimensional signature associated with adduct presence. Building on these observations, we further explored a signal-based analytical approach to identify characteristic signal changes associated with the adduct directly from normalized signal levels. Our results show that nanopore sequencing can detect and localize a site-specifically incorporated AL-II-dA adduct in a defined sequence context through characteristic deviations in normalized signal levels, dwell time, and base-calling features. This study supports the potential of nanopore sequencing as a new approach for investigating DNA-adduct-associated signal characteristics. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/acs.chemrestox.6c00264.s001 https://figshare.com/articles/journal_contribution/Nanopore_Sequencing_Identification_of_DNA_Aristolochic_Acid_Adducts/34036611 CC BY-NC 4.0