IPA®
IPA-Tox® Analysis
IPA-Tox® is a data analysis capability within IPA that delivers a focused toxicity and safety assessment of candidate compounds that are being examined using toxicogenomics approaches.
IPA-Tox supports:
- Analysis workflows: Analysis of gene expression, microarray, Q-PCR, proteomics, and metabolomics data.
- Hypothesis generation workflows: All IPA-Tox content can be accessed through search and information gathering workflows (non-data analysis workflows), enabling researchers to scrutinize hypotheses generated from pre-clinical assays in the context of evidence from the literature and additional toxicogenomics data (protein levels, metabolite levels).
IPA-Tox reveals biological mechanisms that are related to toxicity (on a molecular, cellular, and biochemical level) to help you confidently identify toxic compounds quickly and early in the discovery process, as well as establish toxicogenomics databases for predictive toxicology. |
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IPA-Tox:
- Helps inform decisions related to lead compound optimization
- Efficiently delivers detailed mechanistic hypotheses underlying tox-specific phenotypes
- Contains pathway content and molecule to phenotype associations that accelerate the interpretation of toxicogenomics data and the generation of reports summarizing findings from toxicity studies
- Enables multi-disciplinary toxicology groups to build a toxicogenomics database
- Provides rapid insights into candidate tissue-specific biomarkers through fully integrated IPA biomarker capabilities
- Provides expert molecular toxicology data interpretation to non-expert users
- Generates new molecular hypotheses that may not have been revealed using traditional toxicology approaches
- Provides evidence to support/reject hypotheses generated from pre-clinical toxicity assays
- Allows easy access to important findings from the scientific literature, including information associated with cardiotoxicity, nephrotoxicity, and hepatotoxicity
IPA is an integral component of toxicity and safety assessment best practices.
(Image adapted from Nature Reviews Genetics 5, 936-948.)
IPA is the leading toxicogenomics platform with the strongest track record of success and adoption in pharma due to the following:
- IPA has best in class toxicology content with unsurpassed breadth, depth and quality.
- IPA is cited more frequently than its nearest competitor in toxicology publications.
- IPA was designed to support multidisciplinary teams of scientists.
- IPA-Tox is a component within IPA, allowing scientists to access the full Ingenuity Knowledge Base – not just the components carved out as tox-specific – in order to tease out mechanisms of toxicity.
Highlights
- Toxicity Lists: Understand mechanistic response of xenobiotic insult through functional gene groupings based on critical biological processes and key toxicological responses.
- Toxicity Functions: Link expression data to clinical chemistry, hematology, and histopathology endpoints.
- Toxicity Lists and Toxicity Functions can be combined to understand pharmacological response, mechanism of action and toxicity for better hypothesis generation.
- Interactive Tox Pathways and Reports: Access and interact with key toxicity pathways and detailed pathway summary information.
- Analysis Summaries: Create an automated, focused, and summarized output of analysis results from toxicogenomics data generated for compounds under investigation.
IPA-Tox Links Toxicogenomic Data to Tox Endpoints and Pathways Derived from Toxicity Content Selected and Curated by Experts
Capabilities
Toxicity Lists
One of the keys to gaining actionable insights from toxicogenomics data is the ability to anchor data to histopathology, clinical chemistry, and disease pathology endpoints (steatosis, necrosis, apoptosis, fibrosis, inflammation), and to understand the molecular processes leading to these endpoints (e.g. oxidative stress response).
To help with this, IPA-Tox includes Toxicity Lists, which are functionally grouped gene sets and pathways that describe critical biological processes and key adaptive, defensive, or reparative responses that result from xenobiotic insult. They enable mechanistic understanding of effects in the liver, kidney, and heart.
Toxicity Lists Features:
- Manually-curated by Ph.D. scientists
- Relevant to drug metabolism
- Cover oxidative stress response
- Include P450 panels, xenobiotic metabolism
- Relevant to hepatic, renal, and cardiac toxicity and function
- Contain fibrosis, cardiac hypertrophy and cell death
Tox Lists: Connect gene expression changes to gene sets representing toxic response
Toxicity Functions
Toxicity Functions link toxicogenomic data to clinical chemistry, hematology and histopathology endpoints. By linking differentially expressed genes to their known role in specific tox endpoints, analysis of toxicogenomics data in IPA-Tox identifies subsets of genes that may be predictive of certain endpoints such as liver necrosis, cholestasis, DNA damage, oxidative stress, etc. which can be used to design and implement in vitro assays to for toxicity screening. Categories cover a wide spectrum of well known drug induced injuries and pathologies useful for the drug discovery and development process, such as:
- Hepatoxicity
- Steatosis, necrosis, fibrosis, glutathione depletion, hepatocellular peroxisome proliferation, and more
- Cardiotoxicity
- Cardiomyopathy, cardiac dilation, fibrosis
- Nephrotoxicity
- Tubular nephrosis, phospholipidosis, kidney weight increase, and more
- Clinical Chemistry & Hematology Assays
Tox Functions: Connect toxicogenomics data to phenotype and endpoints
Prioritization of Tox Functions is based on pre-clinical and clinical pathology endpoints most relevant for toxicogenomics researchers, based on feedback collected across the industry. In addition, genes known to be associated with these endpoints and existing knowledge of biomarker applications in the clinic is provided in IPA via well integrated links to clinical biomarker content.
Integrated Biomarker Content: IPA –Tox incorporates knowledge from the IPA-Biomarker to identify genes<br>
already in use in the clinic as biomarkers of safety
Interactive Tox Pathways and Reports
Interactive toxicity pathways allow you to integrate and view key information, including gene expression changes or other toxicogenomic data, related pathology endpoints, and clinical biomarkers. Tox Pathway Reports provide quick and easy information about well-known mechanistic toxicity pathways. They identify related biological processes, diseases, genes and chemicals associated with a pathway, drugs that target the pathway, and more.
Interactive Toxicity Pathway and Pathway Report: Explore key toxicity pathway information
Analysis Summaries for Toxicology
Analysis Summaries create an automated and focused output of toxicity and safety data for compounds under evaluation, providing a mechanistic toxicity overview for a toxicogenomics dataset of interest. They include top scoring molecular interaction networks, toxicity functions, toxicity lists and pathways, and differentially expressed genes.
Analysis Summary: Automated output of relevant toxicity information from a dataset
To learn more about the content used by IPA-Tox, click here
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