1. High-Performance Data Processing Workflow Incorporating Effect-Directed Analysis for Feature Prioritization in Suspect and Nontarget Screening
- Author
-
Jonkers, Tim J H, Meijer, Jeroen, Vlaanderen, Jelle J, Vermeulen, Roel C H, Houtman, Corine J, Hamers, Timo, Lamoree, Marja H, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, E&H: Environmental Chemistry and Toxicology, AIMMS, E&H: Environmental Health and Toxicology, IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
- Subjects
Chemistry(all) ,TTR-binding ,General Chemistry ,effect-directed analysis ,Gas Chromatography-Mass Spectrometry ,Mass Spectrometry ,Article ,Workflow ,bioassay ,antibiotic ,Toxicity Tests ,Humans ,Environmental Chemistry ,Biological Assay ,suspect and nontarget screening ,environment - Abstract
Effect-directed analysis (EDA) aims at the detection of bioactive chemicals of emerging concern (CECs) by combining toxicity testing and high-resolution mass spectrometry (HRMS). However, consolidation of toxicological and chemical analysis techniques to identify bioactive CECs remains challenging and laborious. In this study, we incorporate state-of-the-art identification approaches in EDA and propose a robust workflow for the high-throughput screening of CECs in environmental and human samples. Three different sample types were extracted and chemically analyzed using a single high-performance liquid chromatography HRMS method. Chemical features were annotated by suspect screening with several reference databases. Annotation quality was assessed using an automated scoring system. In parallel, the extracts were fractionated into 80 micro-fractions each covering a couple of seconds from the chromatogram run and tested for bioactivity in two bioassays. The EDA workflow prioritized and identified chemical features related to bioactive fractions with varying levels of confidence. Confidence levels were improved with the in silico software tools MetFrag and the retention time indices platform. The toxicological and chemical data quality was comparable between the use of single and multiple technical replicates. The proposed workflow incorporating EDA for feature prioritization in suspect and nontarget screening paves the way for the routine identification of CECs in a high-throughput manner., A comprehensive workflow was developed that incorporates effect-directed analysis in suspect and nontarget screening for feature prioritization, allowing for the high-throughput identification of bioactive chemicals of emerging concern.
- Published
- 2022