Negative Predictions for Bacterial Mutagenicity

Derek Nexus contains new expert-derived functionality to provide negative predictions for bacterial in vitro mutagenicity. This feature has been designed to support your post-processing workflows, e.g. by highlighting structural features for further expert assessment as part of ICH M7 compliant submissions.

This functionality further evaluates those compounds which do not fire any bacterial in vitro (Ames test) mutagenicity alerts in Derek Nexus. The query compound is compared to a Lhasa reference set of Ames test data, producing the following outcomes:

Negative predictions only apply to predictions against the Lhasa supplied knowledge base from which the libraries were derived.

Key Benefits

The key benefits are:

Terms Used in the Prediction Navigator

The following prediction terms are used in the Prediction Navigator. An explanation of each term is included in the Prediction Qualification column.

Misclassified features present in query molecule

Unclassified features present in query molecule

Prediction

Prediction Qualification

False

False

Inactive

No misclassified or unclassified features

True

False

Inactive

Contains misclassified features

False

True

Inactive

Contains unclassified features

True

True

Inactive

Contains misclassified and unclassified features

Reasoning Explorer Descriptions

All negative predictions are 'Inactive'. These predictions are further qualified by detailing the misclassified and unclassified features. Selecting the Prediction Qualification offers full descriptions of the terms in the Reasoning Explorer. The descriptions are:

Term

Description

No misclassified or unclassified features

The query structure does not match any structural alerts or examples for mutagenicity in Derek. Additionally, the query structure does not contain any unclassified or misclassified features and is consequently predicted to be inactive in the bacterial in vitro (Ames) mutagenicity test. 

Contains misclassified features

Features of the query structure (highlighted in the structure panel) were not found in the Lhasa Ames test reference set but have been observed in mutagens that do not match (bacterial in vitro) mutagenicity structural alerts in Derek. The relationship between these features and mutagenic activity may be coincidental or contributory. However, as the query structure does not match any structural alerts or examples for mutagenicity in Derek, it is predicted to be inactive in the bacterial in vitro (Ames) mutagenicity test.

Contains unclassified features

The query structure contains features (highlighted in the structure panel) that were not found in the Lhasa Ames test reference set and does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Derek. It is predicted to be inactive in the bacterial in vitro (Ames) mutagenicity test.

Contains misclassified and unclassified features

The query structure contains both misclassified and unclassified features, which are highlighted in the structure panel.

  • The misclassified features were found in the Lhasa Ames test reference set and have been observed in mutagens that do not match (bacterial in vitro) mutagenicity structural alerts in Derek. The relationship between these features and mutagenic activity may be coincidental or contributory.

  • The unclassified features were not found in the Lhasa Ames test reference set.

As the query structure does not match any structural alerts or examples for mutagenicity in Derek, it is predicted to be inactive in the bacterial in vitro (Ames) mutagenicity test.