InterPred: a webtool to predict chemical autofluorescence and luminescence interference.

Area of Science:

• Toxicology
• Computational Chemistry
• Biotechnology

Background:

• High-throughput screening (HTS) is crucial for drug development and chemical hazard assessment, often employing fluorescence and luminescence assays.
• These assays are susceptible to chemical interference, leading to up to 10% false positives due to light spectrum interactions.
• The US Tox21 research consortium relies heavily on these technologies for large-scale chemical screening.

Purpose of the Study:

• To introduce InterPred (version 1.0), a novel webserver designed to predict chemical interference in HTS assays.
• To provide a platform for characterizing and mitigating chemical-assay interference, particularly in fluorescence and luminescence-based assays.
• To enable prediction of chemical interference probability across various cellular and technological conditions.

Main Methods:

• Development of InterPred based on the first large-scale chemical screening effort focused on assay interference.
• Integration of 17 quantitative structure-activity relationship (QSAR) models utilizing advanced machine learning techniques.
• Application of InterPred models to the comprehensive Distributed Structure-Searchable Toxicity (DSSTox) Database, encompassing approximately 800,000 chemicals.

Main Results:

• Successful development and deployment of the InterPred webserver for predicting chemical interference.
• Demonstrated application of the models across a vast chemical database, highlighting the platform's scalability.
• Characterization of chemical-assay interference using specific Tox21 assays measuring autofluorescence and luciferase inhibition.

Conclusions:

• InterPred offers a valuable tool for reducing false positives in HTS by predicting chemical interference.
• The platform enhances the reliability and efficiency of drug development and chemical hazard assessment programs.
• InterPred provides a publicly accessible resource (https://sandbox.ntp.niehs.nih.gov/interferences/) for researchers to assess potential chemical interferences.