Genetox Expert Alerts Suite

Genetox Expert Alerts Suite

Rules-based System Designed to Support the ICH M7 Guidelines on Impurities


The Leadscope Expert Alerts Suite is an expert rule-based system designed to address the needs of regulators and bio-pharmaceutical scientists responsible for implementing the ICH M7 guidance. The alert knowledge base was built using a quantitative assessment of publicly-cited alerts from a large database of Ames assay testing results. For each alert, activating and deactivating factors are enumerated through a systematic analysis of the available Ames data and the literature. The alerts are organized hierarchically, to precisely define the relationship between any alerts containing any specific sub-classes of concern. This rule base is annotated with plausible mechanisms collected from the literature. This linkage between the data and the biological interpretation of the alerts is critical in supporting a transparent assessment of the results.


  • Genetic Toxicity Alert knowledge base built from publicly-cited alerts
  • A confidence score accompanies each positive or negative call for each alert
  • Predictions only made for compounds within the domain of applicability
  • Scientists can "drill-down" to examine citations, mechanisms, and examples for each alert

Version 2.0 Updates

Incorporating proprietary knowledge
  • Leadscope established a knowledge-sharing program with corporate sponsors to improve the performance of the expert alerts
  • Knowledge from proprietary data was used to increase the specificity (i.e. removing false positives) for predicting primary aromatic amines by 39%
  • This knowledge also substantially improved the performance of many alerts by refining alert definitions and adding new alerts
Expert Alerts v2.0 status
  • The reference set of compounds defining the domain of the expert alerts increased from 7,304 to 10,295 compounds with experimentally measured bacterial mutation data
  • The system now contains 290 distinct validated alerts
  • Performance of the v1 and v2 of the expert alerts has been quantified against a validation test set of 14,751 compounds including:
    • 10,295 compounds from the Leadscope expert alerts reference set
    • 4,021 compounds from the National Institute for Health Science, Japan
    • 6,512 compounds from the Hansen set
  • The overall accuracy increased by over 4%, with the overall specificity increasing by over 6%

    Comparison of the predictivity of the v1.0 and v2.0 expert alerts

    Download the latest white paper detailing the Genetox Expert Alerts Suite


    • Windows Vista, 7, or 8+ with a minimum 1.0GHz processor, 1.0 GB of available memory, and 10 GB of available disk space