CEBS--Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data.

CEBS (Chemical Effects in Biological Systems) is an integrated public repository for toxicogenomics data, including the study design and timeline, clinical chemistry and histopathology findings and microarray and proteomics data. CEBS contains data derived from studies of chemicals and of genetic alterations, and is compatible with clinical and environmental studies. CEBS is designed to permit the user to query the data using the study conditions, the subject responses and then, having identified an appropriate set of subjects, to move to the microarray module of CEBS to carry out gene signature and pathway analysis. Scope of CEBS: CEBS currently holds 22 studies of rats, four studies of mice and one study of Caenorhabditis elegans. CEBS can also accommodate data from studies of human subjects. Toxicogenomics studies currently in CEBS comprise over 4000 microarray hybridizations, and 75 2D gel images annotated with protein identification performed by MALDI and MS/MS. CEBS contains raw microarray data collected in accordance with MIAME guidelines and provides tools for data selection, pre-processing and analysis resulting in annotated lists of genes of interest. Additionally, clinical chemistry and histopathology findings from over 1500 animals are included in CEBS. CEBS/BID: The BID (Biomedical Investigation Database) is another component of the CEBS system. BID is a relational database used to load and curate study data prior to export to CEBS, in addition to capturing and displaying novel data types such as PCR data, or additional fields of interest, including those defined by the HESI Toxicogenomics Committee (in preparation). BID has been shared with Health Canada and the US Environmental Protection Agency. CEBS is available at http://cebs.niehs.nih.gov. BID can be accessed via the user interface from https://dir-apps.niehs.nih.gov/arc/. Requests for a copy of BID and for depositing data into CEBS or BID are available at http://www.niehs.nih.gov/cebs-df/.

Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application.

MOTIVATION: The CEBS data repository is being developed to promote a systems biology approach to understand the biological effects of environmental stressors. CEBS will house data from multiple gene expression platforms (transcriptomics), protein expression and protein-protein interaction (proteomics), and changes in low molecular weight metabolite levels (metabolomics) aligned by their detailed toxicological context. The system will accommodate extensive complex querying in a user-friendly manner. CEBS will store toxicological contexts including the study design details, treatment protocols, animal characteristics and conventional toxicological endpoints such as histopathology findings and clinical chemistry measures. All of these data types can be integrated in a seamless fashion to enable data query and analysis in a biologically meaningful manner. RESULTS: An object model, the SysBio-OM (Xirasagar et al., 2004) has been designed to facilitate the integration of microarray gene expression, proteomics and metabolomics data in the CEBS database system. We now report SysTox-OM as an open source systems toxicology model designed to integrate toxicological context into gene expression experiments. The SysTox-OM model is comprehensive and leverages other open source efforts, namely, the Standard for Exchange of Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data standard for capturing toxicological information for animal studies and Clinical Data Interchange Standards Consortium (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the exchange of clinical data. Such standardization increases the accuracy of data mining, interpretation and exchange. The open source SysTox-OM model, which can be implemented on various software platforms, is presented here. AVAILABILITY: A universal modeling language (UML) depiction of the entire SysTox-OM is available at http://cebs.niehs.nih.gov and the Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. Currently, the public toxicological data in CEBS can be queried via a web application based on the SysTox-OM at http://cebs.niehs.nih.gov CONTACT: xirasagars@saic.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CEBS object model for systems biology data, SysBio-OM.

MOTIVATION: To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). RESULTS: To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the MicroArray Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. AVAILABILITY: A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/SysBioOM/. The Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. The database and interface are being built to implement the model and will be available for public use at http://cebs.niehs.nih.gov.

Systems toxicology and the Chemical Effects in Biological Systems (CEBS) knowledge base.

The National Center for Toxicogenomics is developing the first public toxicogenomics knowledge base that combines molecular expression data sets from transcriptomics, proteomics, metabonomics, and conventional toxicology with metabolic, toxicologcal pathway, and gene regulatory network information relevant to environmental toxicology and human disease. It is called the Chemical Effects in Biological Systems (CEBS) knowledge base and is designed to meet the information needs of "systems toxicology," involving the study of perturbation by chemicals and stressors, monitoring changes in molecular expression and conventional toxicological parameters, and iteratively integrating biological response data to describe the functioning organism. Based upon functional genomics approaches used successfully in analyzing yeast gene expression data sets, relational and descriptive compendia will be assembled for toxicologically important genes, groups of genes, single nucleotide polymorphisms (SNPs), and mutant and knockout phenotypes. CEBS data sets will be fully documented in the experimental protocol and therefore searchable by compound, structure, toxicity end point, pathology and point, gene, gene group, SNP, pathway, and network as a function of dose, time, and the phenotype of the target tissue. A knowledge base is being developed by assimilating toxicological, biological, and chemical information from multiple public domain databases and by progressively refining that information about gene, protein, and metabolite expression for classes of chemicals and their biological effects in various species. By analogy to the GenBank database for genome sequences, researchers will globally query (or BLAST) CEBS using a transcriptome of a tissue of interest (or a list of outliers) to have the knowledge base return information on genes, groups of genes, metabolic and toxicological pathways, and contextually associated phenotypic information for compounds that display similar response profiles. With high-quality data content, CEBS will ultimately become a resource to support hypothesis-driven and discovery research that contributes effectively to drug safety and the improvement of risk assessments for chemicals in the environment. The CEBS development effort will span a decade or more.