BioMAP® Tox Alert™

Add-on Analysis for Diversity PLUS® Service Projects

The BioMAP Tox Alert is comprised of proprietary algorithms and expert bioinformatic analysis to identify potential mechanisms of toxicity in human patients. This analysis uses data from the 12 BioMAP Systems of Diversity PLUS, which contains early passage primary human cell types from multiple tissues, representing a broad range of human biology and disease. Compounds are interrogated in these complex biological systems to determine their phenotypic impact on physiologically relevant disease biology in terms of efficacy and safety.

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Chemical Safety Applications

  • Translational biology for drug discovery and chemical safety
  • Mechanism scanning for safety pharmacology and investigative toxicology
  • Classification of compounds with unknown mechanisms of action

Tox Alert Analysis Advantages

  • Predictive – Use machine learning to classify compounds by mechanism and identify common toxicities
  • Reproducible – Powered by the 148 biomarker readouts and database of over 4,000 reference compounds of Diversity PLUS
  • Meaningful – Identify adverse outcome pathways associated with actual clinical reactions
 
BioMAP Tox Alert Add-on Service
Service Analysis of concurrent or previously profiled compounds in Diversity PLUS for additional safety and toxicology parameters
Description Tox Alert
  • Mechanism Classification: Results of computational models built for mechanism of action prediction (over 28 predictive models).
  • Toxicity Signature: Test for one of 8 signatures correlated with increased risk of particular toxicity effects in vivo.

Diversity PLUS
  • Annotation: Identification and biological interpretation of relevant BioMAP activities.
  • Similarity Search: Results from unsupervised search for a biologically similar compound from the BioMAP reference database of >4,000 compounds, biologics, approved drugs and experimental agents.
Deliverables
  • Study Report: BioMAP profile plots, results of Tox Alert, annotation of activities with respect to biological significance, results of mechanism prediction and expert data interpretation.
  • Data Report: Log ratio data tables, 95% significance envelope, table of cytotoxicities, table of active readouts.

References:
  • Kleinstreuer, N., K. A. Houck, J. Yang, T. B. Knudsen, D. J. Dix, D. M. Reif, M. Polokoff, and E.L. Berg.  Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms, 2014, Nature Biotechnology, 32:583-591. 
  • Berg, E.L., M.A. Polokoff, A. O’Mahony, D. Nguyen, and X. Li. Elucidating Mechanisms of Toxicity Using Phenotypic Data from Primary Human Cell Systems – a Chemical Biology Approach for Thrombosis-Related Side Effects, Int J Mol Sci. 2015, 16:1008-29. PMID:  25569083