Prioritizing Chemical Candidates from Non-targeted Analysis Using Metadata, Spectral Similarity, and Hazard Scoring...

New approach methodologies like non-targeted analysis (NTA) are increasingly relevant for identifying and monitoring emerging contaminants. Utilizing high-resolution mass spectrometry (HRMS), NTA methods can detect and annotate chemicals without prior knowledge. Yet, NTA results often have associated uncertainties owing, in part, to a lack of standardized methods. To address this challenge, the US Environmental Protection Agency (US EPA) developed the Interface for Processing, Reviewing, and Translating NTA data ("INTERPRET NTA") to support NTA research within its Office of Research and Development (ORD). Previous work demonstrated INTERPRET NTA's capabilities for reviewing and reporting NTA data quality. The current work highlights additional functionalities for retrieving and interpreting chemical results. INTERPRET NTA accesses chemical data from multiple US EPA resources, including (1) chemical metadata from US EPA's Analytical Methods and Open Spectra (AMOS) database, (2) predicted spectra for ∼1.2 million chemical substances within US EPA's DSSTox database, and (3) hazard values from US EPA's Cheminformatics Hazard Module (CHM). De facto water reuse study data with 77 known chemicals were used to demonstrate INTERPRET NTA functions and capabilities. Known chemicals showed higher values for metadata, MS², and hazard scores in 99.0%, 80.5%, and 92.0% of cases, respectively, compared to false positives. Interactive visualizations within INTERPRET NTA facilitate the visual integration of chemical results, highlighting chemical candidates of greatest interest, and allowing review of underlying data. INTERPRET NTA is being prepared for public release, offering researchers a tool for defensible and efficient review and reporting of NTA study results.