Innovative Research for a Sustainable Future www.epa.gov/research Developing tools for high resolution mass spectrometry-based screening via the EPA’s CompTox Dashboard Andrew D. McEachran1,2*, Kamel Mansouri3, Hussein Al-Ghoul4, Alex Chao4, Chris Grulke2, Jon R. Sobus5, and Antony J. Williams2 1Oak Ridge Institute of Science and Education (ORISE) Research Participant, Research Triangle Park, NC 2U.S. Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC 3Integrated Laboratory Systems, Inc., Morrisville, NC | 4Oak Ridge Associated Universities, Research Triangle Park, NC 5U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Research Triangle Park, NC * mceachran.andrew@epa.gov l ORCiD: 0000-0003-1423-330X Problem Definition and Goals The CompTox Dashboard MS-Ready Structures for Database Searching MS/MS Data in NTA/SSA References Acknowledgements 1. Williams, AJ, et al. 2017. The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J Cheminf. https://doi.org/10.1186/s13321-017-0247-6 2. McEachran, AD, et al. 2017. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard. Anal. Bioanal. Chem. 409(7): 1729-1735. doi:10.1007/s00216-016-0139-z 3. McEachran, AD, et al. 2017. A comparison of three chromatographic retention time prediction models. Talanta. https://doi.org/10.1016/j.talanta.2018.01.022 4. McEachran, AD, et al. 2018. “MS-Ready” structures for non-targeted high-resolution mass spectrometry screening studies. J Cheminf. Accepted for publication. 5. Allen, et al. 2015. Competitive fragmentation modeling of ESI-MS/MS spectra for putative metabolite identification. Metabolomics. https://doi.org/10.1007/s11306-014-0676-4 6. Newton, SR, et al. 2018. Suspect screening and non-targeted analysis of drinking water using point-of-use filters. Environ Poll. https://doi.org/10.1016/j.envpol.2017.11.033 Applications The authors would like to thank Emma Schymanski and Christoph Ruttkies for their valuable contributions on the MS-Ready Structures, associated publication, and integration to MetFrag. The authors would also like to thank Reza Aalizadeh and Nikolaos Thomaidis for use of the UOA-RTI software for retention time index prediction (manuscript submitted for publication). The authors would like to acknowledge the Dashboard development team for their efforts in surfacing all functionality. This work was supported in part by an appointment to the ORISE Research Participation Program at the Office of Research and Development, U.S. EPA, through an interagency agreement between the US EPA and DOE. This presentation does not necessarily represent the views or policies of the U.S. Environmental Protection Agency. Chemical metadata for ranking Problem: Non-targeted and suspect screening studies using high resolution mass spectrometry (HRMS) have revolutionized the detection of chemicals in complex matrices. However, data processing remains challenging due to the vast number of chemicals detected in samples, software and computational requirements of data processing, and inherent uncertainty in confidently identifying chemicals from candidate lists. Goals: Develop tools, data, and visualization approaches within an open chemistry resource to provide a freely available software tool to support structure identification and non-targeted analysis. Home page. The CompTox Dashboard (https://comptox.epa.gov) is a comprehensive chemistry resource containing chemistry data on more than 760,000 chemical substances. (Left and Below) To facilitate database searching, structures in DSSTox were processed into their “MS-Ready” form [4]. This processing workflow removes salts and stereochemistry and separates components of mixtures while retaining linkages to the original structure and substance. This enables the form of a structure observed via HRMS to be relat