The ToxFX Analysis Suite combines either Affymetrix GeneChip® Rat Genome 230 2.0 arrays or the reduced feature set Affymetrix GeneChip® Rat ToxFX 1.0 arrays with an Iconix analysis to provide a complete toxicogenomics solution. The gene expression data are interpreted in minutes and presented as a detailed, customized report.
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Each report will display the analysis results of one compound
The user can select up to 3 reference compounds from a set of 316 compounds in DrugMatrix
The key elements of the report are:
Executive Summary The Executive summary is a single-page overview of the complete Report. It presents key signature, pathway responses and gene expression responses along with information on the experimental protocol and experiment quality. It provides a text level view of the report contents presented in a form that can be read in five to ten minutes.
Quality Control The quality control module confirms the correlation among replicate animal treatments before data are submitted for analysis. It is intended to supplement the standard Affymetrix quality controls. Close correlation between replicate animals is a prerequisite for a successful analysis and lack of correlation flags potential errors in the sample labeling or submission.
Drug Signatures Drug Signatures link patterns of gene expression to toxicological endpoints such as histopathology and clinical chemistry as well as to pharmacologic observations and drug structure classes. Drug Signatures translate highly complex gene expression data into language that is more familiar to the toxicologist. The results are easy to interpret, provide an early warning of potential toxicological effects and can be used to generate testable hypotheses and as an entry point for deeper analysis.
P450 Panel The p450 panel is an expression-level screen of key cytochrome p450 genes. This allows early and sensitive screening for a total of 63 different p450 responses. The report provides the expression level response for each transcript as well as an overview of the response to drugs in different tissues across the DrugMatrix database. It is widely understood that the expression levels of many p450 genes are often non-specifically perturbed. Comparison to our reference data set ensures that accurate distinctions can be made between non-specific and relevant changes.
Pathways The pathways provided in the ToxFX report are functional gene groupings based on critical biological processes and key toxicological responses. Many gene products are involved in both biological processes and in adaptive, defensive or reparative responses to a xenobiotic insult. Most pathways in the literature are constructed based only on the biological function of the genes. In contrast, the pathways in the ToxFX report focus on processes important to understanding toxicological responses in liver, kidney and heart. Pathway legends provide descriptions and curated background information for these functions. Pathways and annotations are based on extensive literature surveys and tailored to provide optimal information necessary to understand mechanism of action and mechanism of toxicity.
Gene-level information The report contains expression information on genes that are most significantly perturbed in pathways or are the most consistently up and down regulated in the submitted set of experiments. These up and down regulated genes may act as indicators of responses outside the toxicological pathways represented in the report.
The ToxFX report provides a comprehensive analysis of the Toxicogenomic properties of a specific drug. It is organized in a way that is easy to read and navigate, and it provides the most relevant interprepations that can be used by a drug safety team.
