Top Features of the Tox21Chem Browser Every Researcher Should Know

Advanced Search Strategies in Tox21Chem Browser for High-Throughput Screening

Overview

• Use the Browser to combine assay, chemical, and activity filters to rapidly prioritize hits from the Tox21/ToxCast qHTS dataset.

Key strategies

1. Start with assay selection
   • Pick relevant assay(s) by biological target, pathway, or endpoint (e.g., nuclear receptor binding, cytotoxicity, reporter assays).
2. Use activity metrics, not just binary calls
   • Filter by EC50/AC50 ranges, potency (logAC50), and efficacy to prioritize biologically meaningful responses.
3. Filter by curve-fitting quality
   • Exclude low-confidence curves by requiring high curve class or R-squared and sufficient concentration-response points.
4. Combine orthogonal assays
   • Require activity across multiple related assays (consensus across target assay + downstream pathway readout) to reduce false positives.
5. Control for cytotoxicity and assay interference
   • Cross-filter with cytotoxicity assays and known interference/readout artifacts (fluorescence, luciferase) to remove nonspecific actives.
6. Use chemical properties for triage
   • Apply molecular weight, logP, PAINS or promiscuity filters and remove flagged substances (e.g., reactive electrophiles) to focus on tractable chemistries.
7. Leverage structure-based grouping
   • Search by scaffold or substructure to find series-level SAR; use similarity clustering to prioritize chemotypes with multiple actives.
8. Prioritize with exposure and annotation data
   • Integrate external metadata (use categories, production volume, known uses) when available to focus on high-priority human-relevant chemicals.
9. Export and overlay results
   • Overlay concentration-response curves from multiple assays to compare potency/efficacy; export flat files for downstream modeling or detailed QC.
10. Iterative refinement
    • Start broad, inspect top hits visually, then tighten