TOXcms

TOXcms analyzes mass spectrometry-based metabolomics dose-response data to evaluate dose-dependent changes and group metabolomic signals and other assay readouts, enabling detection of on- and off-target effects of small-molecule drugs and toxicants.

Key Features:

• Dose-response evaluation: Employs statistical techniques to evaluate dose-response trends across each metabolomic signal.
• User-defined tolerances: Evaluation of dose-response trends is guided by user-defined tolerances.
• Signal grouping: Groups signals that exhibit similar dose-response patterns to identify related responses.
• Platform integration: Built upon the XCMS framework and compatible with other metabolomic data-processing platforms.
• Multi-assay integration: Integrates additional datasets such as respirometry, cell death assays, and other omic technologies to correlate dose-response relationships across measurements.
• Off-target detection: Detects off-target effects and distinguishes metabolic responses attributable to different protein targets with varying potencies, demonstrated with metformin and etomoxir.
• Mass spectrometry data processing: Processes mass spectrometry-based metabolomics data generated from samples treated across a range of compound concentrations.

Scientific Applications:

• Mechanism elucidation: Elucidates biochemical mechanisms underlying compound actions by resolving distinct dose-dependent metabolic phenotypes.
• Pharmacology and toxicology: Identifies off-target interactions of pharmaceuticals and toxicants to inform pharmacology and toxicology studies.
• Cross-assay correlation: Correlates metabolomic dose-response patterns with respirometry, cell death assays, or other omic readouts.
• Multi-target compound assessment: Evaluates chemicals that affect multiple protein targets with varying potencies.

Methodology:

Processes mass spectrometry-based metabolomics data using statistical techniques to evaluate dose-response trends across each metabolomic signal; evaluation is guided by user-defined tolerances and used to group signals with similar patterns, implemented on the XCMS framework.