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Toxygates: interactive toxicity analysis on a hybrid microarray and linked data platform
Johan Nyström-Persson1, Yoshinobu Igarashi, Maori Ito
1National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki City, Osaka 567-0085, Japan and Centre for Knowledge Structuring, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Motivation:
In early stage drug development, it is desirable to assess the toxicity of compounds as quickly as possible. Biomarker genes can help predict whether a candidate drug will adversely affect a given individual, but they are often difficult to discover. In addition, the mechanism of toxicity of many drugs and common compounds is not yet well understood. The Japanese Toxicogenomics Project provides a large database of systematically collected microarray samples from rats (liver, kidney and primary hepatocytes) and human cells (primary hepatocytes) after exposure to 170 different compounds in different dosages and at different time intervals. However, until now, no intuitive user interface has been publically available, making it time consuming and difficult for individual researchers to explore the data.
Results:
We present Toxygates, a user-friendly integrated analysis platform for this database. Toxygates combines a large microarray dataset with the ability to fetch semantic linked data, such as pathways, compound-protein interactions and orthologs, on demand. It can also perform pattern-based compound ranking with respect to the expression values of a set of relevant candidate genes. By using Toxygates, users can freely interrogate the transcriptome's response to particular compounds and conditions, which enables deep exploration of toxicity mechanisms.
Insights
Toxygates offers a user-friendly platform to analyze toxicogenomics data, aiding early drug development by exploring compound toxicity mechanisms and identifying potential biomarkers through integrated analysis of gene expression and linked biological data.
Area of Science:
- Toxicogenomics
- Computational Biology
- Drug Development
Background:
- Assessing compound toxicity early in drug development is crucial but challenging due to difficulties in biomarker discovery and understanding toxicity mechanisms.
- The Japanese Toxicogenomics Project database contains extensive microarray data from rat and human cells exposed to various compounds, but lacks an accessible interface.
- Existing data exploration methods are time-consuming and difficult for researchers.
Purpose of the Study:
- To develop an intuitive, user-friendly platform for exploring the Japanese Toxicogenomics Project database.
- To enable efficient analysis of compound-induced toxicity and facilitate the discovery of toxicity mechanisms.
- To integrate transcriptomic data with semantic linked data for deeper biological insights.
Main Methods:
- Development of Toxygates, an integrated analysis platform.
- Integration of a large microarray dataset with semantic linked data (pathways, compound-protein interactions, orthologs).
- Implementation of pattern-based compound ranking using candidate gene expression values.
Main Results:
- Toxygates provides a user-friendly interface for interrogating transcriptomic responses to compounds.
- The platform enables on-demand fetching of relevant biological data, enhancing analysis.
- Users can perform pattern-based compound ranking to identify potential toxicity signatures.
Conclusions:
- Toxygates facilitates deep exploration of toxicity mechanisms by enabling free interrogation of transcriptomic data.
- The platform supports early-stage drug development by providing rapid toxicity assessments.
- Toxygates enhances the utility of large toxicogenomics datasets for researchers.
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