Chemical Effects in Biological Systems—Data Dictionary (CEBS-DD): A Compendium of Terms for the Capture and Integration of Biological Study Design Description, Conventional Phenotypes, and ‘Omics Data

Jennifer Fostel 3 4 Danielle Choi 3 4 Craig Zwickl 0 3 Norman Morrison 2 3 Asif Rashid 3 4 6 Atif Hasan 3 6 Wenjun Bao 3 5 Ann Richard 3 5 Weida Tong 3 k Pierre R. Bushel 3 kj Roger Brown 3 kk Maribel Bruno 3 kj Michael L. Cunningham 1 3 David Dix 3 5 William Eastin 1 3 Carlos Frade 3 4 Alex Garcia 0 3 Alexandra Heinloth 3 kj Rick Irwin 1 3 Jennifer Madenspacher 3 kj B. Alex Merrick 3 kj Thomas Papoian 3 \\ Richard Paules 3 kj Philippe Rocca-Serra 0 3 Assunta-Susanna Sansone 0 3 James Stevens 0 3 Kenneth Tomer 3 kj Chihae Yang 3 Michael Waterskj 3 0 Lilly Research Laboratory , Greenfield, Indiana 46140 1 U.S. National Toxicology Program , Research Triangle Park, North Carolina 27709 2 National Environmental Research Council (NERC), University of Manchester , Manchester M13 9PL , U.K. 3 The information in this document has been funded in part by the National Institute of Environmental Health Sciences, the National Center for Toxicoge- nomics, and the U.S. Environmental Protection Agency. It has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Toxicogenomics , PO Box 12233 Mail Drop F1-05, 111 Alexander Drive, Research Triangle Park NC 27709-2233. Fax: (919) 541-1460 4 LIMT Lockheed Martin Information Technology (LMIT) , Research Triangle Park, North Carolina 27709 5 U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711 6 Alpha-Gamma Technologies, Inc. , Raleigh, North Carolina 27609 acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202). - A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highlyparallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on The ability to archive, retrieve, and exchange high content data sets, including transcript profiles, among laboratories, industries, and government agencies is a crucial step in exploiting the power of high content technologies to describe the response of an organism to the environment. A key step in achieving this end is to develop a publicly accessible database and associated standards for the exchange of data with associated metadata that provide experimental context so that the data can be mined efficiently and intuitively. Currently no national or international standard provides the necessary nucleus of metadata standards around which such a database can be organized to facilitate the facile electronic exchange of information among interested stakeholders. Therefore, a consortium of the stakeholders from the private and public sectors have contributed to the development of a data dictionary containing terms, definitions, relationships, and controlled vocabularies for the Chemical Effects in Biological Systems (CEBS) Knowledgebase. The CEBS Knowledgebase is being developed at the National Center for Toxicogenomics (NCT). Currently still early in the development process, CEBS will become a public toxicogenomics resource integrating traditional toxicology and pathology phenotype data with data from highly parallel technologies, such as from microarray or proteomics studies, in biological context using the Study Design Description (Waters, 2004; Waters et al., 2003). To accomplish this, CEBS captures the relevant characteristics of Study Subjects and methods (Protocols), and the Study Timeline on which Events such as treatment, animal care, and exit (euthanasia) occur. These characteristics are collectively termed the Study Design Description. The CEBS Data Dictionary (CEBS-DD) includes the terms, definitions, and relationships to support the accurate capture of elements of the Study Design Description by CEBS. Once the Study Design Description has been captured, it can be used to organize and annotate the data derived from Study Subjects and to display the data in a meaningful biological context within CEBS. The challenges inherent in building the CEBS-DD are twofold. First, the minimal information needed to interpret a toxicogenomics Study must be identified to ensure that data deposited in CEBS meet a common minimum standard. This need is satisfied by CEBS-DD, which extends the original Minimal Information about a Microarray Experiment/Toxicology (MIAME/Tox) standard developed by the NCT, the European Bioinformatics Institute (EBI) and the International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) (www.mged.org/MIAME1.1-DenverDraft.DOC). The minimal information requirement is highly dependent upon the biological conduct of the experiment, and has been extended in the CEBS-DD primarily within the framework of an acute toxicity Study. CEBS will offer a graphical user interface (GUI) to capture minimal Study information (see Figure 1). The second challenge, also met by the CEBS-DD, is to define the maximum information that can be provided by a data depositor. CEBS must be able to accurately capture any and all relevant pieces of information about the Study and then interpret and present the data in a way that permits querying by the CEBS user. In most cases well-annotated sources are already in an electronic format; thus, it is anticipated that transfer to CEBS of data from richly annotated studies will occur electronically rather than through a manual input web interface, and that the CEBS-DD will facilitate the writing of parsers by supplying annotation and synonyms for different data formats. This electronic parsing would occur apart from the CEBS web interfac (...truncated)