Using the US EPA’s CompTox Chemistry Dashboard for structure identification and non-targeted analyses
Antony J. Williams, Andrew D. McEachran, Seth Newton, Kristin Isaacs, Katherine Phillips, Nancy Baker, Christopher Grulke and Jon R. Sobus
High resolution mass spectrometry (HRMS) and non-targeted analysis (NTA) are advancing the identification of emerging contaminants in environmental matrices, improving the means by which exposure analyses can be conducted. However, confidence in structure identification of unknowns in NTA presents challenges to analytical chemists. Structure identification requires integration of complementary data types such as reference databases, fragmentation prediction tools, and retention time prediction models. The goal of this research is to optimize and implement structure identification functionality within the US EPA’s CompTox Chemistry Dashboard, an open chemistry resource and web application containing data for ~760,000 substances. Rank-ordering the number of sources associated with chemical records within the Dashboard (Data Source Ranking) improves the identification of unknowns by bringing the most likely candidate structures to the top of a search results list. Database searching has been further optimized with the generation of MS-Ready Structures. MS-Ready structures are de-salted, stripped of stereochemistry, and mixture separated to replicate the form of a chemical observed via HRMS. Functionality to conduct batch searching of molecular formulae and monoisotopic masses was designed and released to improve searching efforts. Finally, a scoring-based identification scheme was developed, optimized, and surfaced via the Dashboard using multiple data streams contained within the database underlying the Dashboard. The scoring-based identification scheme improved the identification of unknowns over previous efforts using data source ranking alone. Combining these steps within an open chemistry resource provides a freely available software tool for structure identification and NTA. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.