title: Pathway analysis tools and toxicogenomics reference databases for risk assessment.
abstract: The pharmaceutical industry has begun to leverage a range of new technologies (proteomics, pharmacogenomics, metabolomics and molecular toxicology [e.g., toxicogenomics]) and analysis tools that are becoming increasingly integrated in the area of drug discovery and development. The approach of analyzing the vast amount of toxicogenomics data generated using molecular pathway and networks analysis tools in combination with analysis of reference data will be the main focus of this review. We will demonstrate how this combined approach can increase the understanding of the molecular mechanisms that lead to chemical-induced toxicity and application of this knowledge to compound risk assessment. We will provide an example of the insights achieved through a molecular toxicology analysis based on the well-known hepatotoxicant lipopolysaccharide to illustrate the utility of these new tools in the analysis of complex data sets, both in vivo and in vitro. The ultimate objective is a better lead selection process that improves the chances for success across the different stages of drug discovery and development.
authors.affiliation: Ingenuity Systems, 1700 Seaport Blvd, Redwood City, CA 94063, USA. bganter@ingenuity.com
authors.forename: Brigitte
authors.initials: B
authors.lastname: Ganter
authors.forename: Nadine
authors.initials: N
authors.lastname: Zidek
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hewitt
authors.forename: Dieter
authors.initials: D
authors.lastname: Müller
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Vladimirova
mesh_terms: D000818:Animals; D030541:Databases, Genetic; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D015398:Signal Transduction / Q000235:genetics*; D043922:Toxicogenetics
chemical_list: D008070:Lipopolysaccharides