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

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.