Systems toxicology analysis for MetaCore™ and MetaDrug™

New in the latest release of ToxHunter:

• New enrichment calculation and table export for xenobiotic metabolism enzymes and transcription factors
• Biomarker and toxicant annotations for xenobiotic-induced pathology in 2 additional organs, esophagus and glandular stomach

ToxHunter is a systems toxicology knowledgebase and data analysis package designed for the assessment of safety liabilities of drugs, environmental contaminants and other xenobiotics at all stages of discovery and development. ToxHunter is available as an add-on for GeneGo MetaCore and MetaDrug systems biology and systems pharmacology solutions, and integrates seamlessly with these products to provide a powerful tool for toxicogenomics and systems toxicology research.

ToxHunter adds to the information mining and data analysis power of the GeneGo platform with a comprehensive, searchable database of gene, protein and metabolite associations to chemical toxicity, new toxicity-related pathway maps, and tools for visualization and filtering of systems toxicology information on pathway maps and biological interaction networks. Experiments can easily be designed to model specific pathologies, to investigate mechanisms and pathways of toxicity, or to identify safety biomarkers. Molecular safety data can be analyzed in the context of previously reported effects and known signaling and metabolic networks. Automated data analysis and reporting workflows enable rapid interpretation and reporting of experimental results.

Key ToxHunter features include

• Comprehensive ontology of histopathology and clinical adverse drug effects, with full-text literature annotation of gene, protein, compound and small molecule biomarker associations to toxicity endpoints in key target organs. Allows investigations at multiple levels of detail.
• Detailed toxicity content for liver, kidney, heart, lung and other key target organs of toxicity.
• Simple key-word and Boolean searching across toxicity categories for pathology terms, gene, protein or metabolite biomarkers of toxicity.
• Toxicity-focused pathway maps, organized into biological categories relevant to mechanisms of toxicity. Maps cover key modes and mechanisms of toxic action and response.
• Built-in support for commercial microarrays, and automatic translation of common protein and metabolite identifiers. Facilitates analysis of multiple data types independently or in concert.
• New enrichment function for GeneGo Toxicity Biomarker genes gives detailed view of experimental associations to pathological processes.
• Enrichment categories for biological function, disease biomarkers, drug target networks, metabolic networks, and more, provide a comprehensive overview of the effects of compound treatments on biological systems.
• Best in class database of molecular interactions (MetaBase™) and multiple tools for experimental comparison, network building, and interactome analysis identify relationships between experimental datasets, illuminate key “hidden hub” controlling factors and facilitate the identification of biomarkers of toxicity.
• QSAR prediction of pathological outcomes from chemical structures (with MetaDrug)
• Easy to use workflows for common systems toxicology queries, and automated report generation tools rapidly translate data into actionable results.

“I like your MetaTox very much. The information is very rich!!”

“ToxHunter predicted the correct pathways, based on what they already knew.”

Rather than taking a “developer knows best” approach to MetaTox, GeneGo has brought together a panel of end-user scientists to advise and prioritize product development. A steering committee of representatives from partner organizations meet face-to-face once a year, and via web conference, quarterly, to discuss the issues being faced in drug safety today, the molecular data types being generated as part of the safety assessment process, and the tools and supporting information content necessary to make best use of these toxicogenomics data. GeneGo’s MetaTox program, led by Richard Brennan, Ph.D. DABT, takes the partners’ recommendations and priorities, and translates them into usable tools. Current MetaTox Partnership members include representatives from the pharmaceutical industry and, critically, from the FDA.

Key advantages of MetaTox Partnership

• Comprehensive suite of GeneGo software included in membership fee
• 6-month exclusivity and a permanent license to all MetaTox software developed by the partnership program
• Unlimited access to the MetaTox systems toxicology tool during the project lifecycle
• Direct input into the development of additional content and tools
• Tissue coverage, toxicity maps and pre-built networks specifically tailored to your program needs
• Automated toxicity data analysis workflows
• A “finger on the pulse” of FDA’s current thinking on the use, interpretation and submission of systems toxicology data and safety biomarkers for drug registration

Additional MetaTox features under development through partner involvement

• Modeling of toxicity endpoints to provide direct prediction of outcomes from chemical structure, or from ‘omics data with direct association to mechanisms of toxicity
• Comprehensive coverage of target organs of toxicity
• Additional workflows to automate complex queries such as:
  • Comprehensive evaluation of a drug target from a safety perspective
  • Identifying potential associations between observed adverse effects and the drug target
  • Identification of transcription factors driving observed experimental changes
  • Analysis of compound effects on drug metabolizing enzymes

The MetaTox Partnership program is in the 2nd year of a 3-year program. Membership remains open to up to 3 more partners. For more information on joining the MetaTox Partnership program, contact Julie Bryant at 1-858-756-7996 or Julie@genego.com.