Environmental and dietary genotoxicants, endogenous electrophiles, and ionizing radiation damage the human genome through covalent modifications of DNA, known as DNA adducts. DNA adductomic analysis is a newly established field for the characterization of DNA damage. There is currently no DNA adduct mass spectral database, which greatly limits the power of DNA adductomics analysis. Over 200 authentic DNA adduct standards are being collected from 36 domestic and international collaborators and commercial sources. MSn spectra of the already-received 90 standards are being acquired on Orbitrap and Q-TOF instruments at the MS2 scan stage with multiple collision energies (CE). MS3 fragmentation is also performed on the Orbitrap instrument using data-dependent-MSn data collection, allowing MS2 and MS3 scans at multiple collision energies to be collected in a single injection. A custom bioinformatics workflow has been established, which uses a number of data processing steps to select high quality Orbitrap and Q-TOF MS spectra for inclusion into the spectral library. These steps include selection of spectra arising from precursors with a verified low ppm mass error and sufficient abundance (&gt;50% of the total ion current for the scan), and subsequent data processing using MS-FINDER (v 3.2) for product ion annotation. Consensus spectra are then created for incorporation into MassBank of North America (MoNA), PubChem, and mzCloud (Thermo Fisher Scientific). Related adduct metadata such as the common and IUPAC names of the adducts, canonical and isomeric SMILES notations, and MS scanning parameters will be uploaded to PubChem, from where data will be automatically propagated to other public databases such as Human Metabolome Database (HMDB). MoNA, PubChem, and mzCloud have agreed to provide technical assistance for the integration of our annotated mass spectra and adduct information into their databases.

Development of DNA Adductome Mass Spectral Database

ACS Fall 2020 Virtual Meeting

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