MetaTox™ for Systems Toxicology Research

MetaTox is a GeneGo-pharma-FDA partnership developing a comprehensive systems toxicology suite designed for compound safety assessment in chemical and pharmaceutical R&D. Applications include lead discovery and optimization, investigative, molecular and mechanistic toxicology, biomarker identification and validation. MetaTox provides scientists with content and tools to analyze and interpret molecular toxicology data from human and animal models in relation to chemical-induced changes, and their potential adverse effects.

Key MetaTox 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 and other key target organs of toxicity
• Searchable database of toxicity findings, toxicants and gene biomarkers of pathology.
• 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
• Easy to use workflows for common systems toxicology queries, and automated report generation tools rapidly translate data into actionable results

MetaTox content will be available for purchase as part of GeneGo’s suite of software solutions in 2010.

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 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 MetaTox 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.