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

Michael Waters 2 Stanley Stasiewicz 2 B. Alex Merrick 2 Kenneth Tomer 2 Pierre Bushel 2 Richard Paules 2 Nancy Stegman 2 Gerald Nehls 2 Kenneth J. Yost 1 C. Harris Johnson 1 Scott F. Gustafson 1 Sandhya Xirasagar 1 Nianqing Xiao 1 Cheng-Cheng Huang 1 Paul Boyer 1 Denny D. Chan 1 Qinyan Pan 1 Hui Gong 1 John Taylor 0 Danielle Choi 4 5 Asif Rashid 5 Ayazaddin Ahmed 3 Reese Howle 3 James Selkirk 2 Raymond Tennant 2 Jennifer Fostel 5 0 Large Scale Biology Corporation , 3333 Vaca Valley Parkway, Vacaville, CA 95688 1 Science Applications International Corporation , 1710 SAIC Drive, McLean, VA 22101 2 NIEHS, National Center for Toxicogenomics , PO Box 12233, Research Triangle Park , NC 27709 3 Alpha Gamma Technologies, Inc., 4700 Falls of Neuse Road, Suite 350, Raleigh, NC , 27609, USA 4 Research Triangle Institute , PO Box 12194, Research Triangle Park , NC 27709 5 Lockheed Martin Information Technologies, PO Box 12233, Research Triangle Park , North Carolina 27709 - 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/. CEBS (Chemical Effects in Biological Systems) is a public repository for toxicogenomics data developed by the National Center for Toxicogenomics (NCT) within the National Institute of Environmental Health Science (NIEHS). Development of CEBS began in 2002 (1) and focused first on capture of microarray and proteomics data. The CEBS SysBio Object Model (2), based on MIAME (3) and MIAPE Standard (4), was used for this portion of the development of CEBS. CEBS1 was released in August 2003, followed by the start of development of CEBS2. The aim of the second stage of CEBS development was to integrate study design and toxicological assay data with theomics data captured in CEBS. Thus, the CEBS SysTox Object Model (5) and the CEBS Data Dictionary (CEBS-DD) (6) were developed to permit accurate management of study data. CEBS2 was released in November 2006. As of July 2007, there are 27 toxicogenomics studies in CEBS. A study refers to an observational or perturbational experiment carried out over a defined timeline to understand a biological system, address a scientific question and/or to generate hypotheses. Of the 27 studies, 22 are of rat, 4 are of mouse and 1 is of Caenorhabditis elegans. Twenty-six of the studies have associated microarray data, one has proteomics data. Companies which have published data in CEBS include Iconix Biosciences (http://www.iconixpharm.com/), Johnson & Johnson (7,8), Pfizer Inc. (9) and Sankyo Co., Ltd (10). Other data in CEBS have been submitted by researchers at the National Cancer Institute (11,12), the University of Tennessee (1315), the University College of London (16,17), the HESI Toxicogenomics Committee (18,19) and the Toxicogenomics Research Consortium (submitted). Additional data have been deposited in CEBS from inhouse studies carried out at the NIEHS (20) and at the National Toxicology Program (NTP) (21,22). CEBS can store data from studies of laboratory animals, cultured cells or humans. Most studies in CEBS contain observations or measurements made of the study subjects and of specimens such as blood or tissue sections derived from these subjects. The objective of CEBS is to permit the user to integrate various data types and studies. The CEBS user can select groups of subjects drawn from different studies, based on subject responses or study conditions. Once the subjects are selected, any associated microarray data can be analyzed to produce lists of annotated genes that can shed light on the biological and toxicological processes occurring in the subjects. MATERIALS AND METHODS Scope and Utility of CEBS CEBS is the first public repository designed to integrate toxicological, histopathological and other biological measures withomics data. A number of other databases, for instance the Gene Expression Omnibus (GEO) (23,24), capture microarray data and information about the sample treatment. The ArrayExpress database (25) captures observations and measures taken on the study subject concurrently with preparation of the tissue for microarray analysis (26). A distinguishing feature of CEBS is that the data captured from toxicogenomics studies includes observations made of the subject throughout the study timeline, potentially both before and after a specimen was taken for toxicological, histopathological or other biological analysis. Since the descriptions of the protocols used in the study and associated analyses are captured using controlled vocabularies rather than in free text form, these data are available for effective filtering and query. These protocols, measures and temporal events are useful in anchoring the transcriptomics or proteomics profile displayed by the specimen within the time- and dose-dependent biological responses seen in the study. Thus CEBS supports phenotypic anchoring (2731), defined as the linking of microarray or proteomics data with a pathophysiological phenotype. CEBS includes both microarray and proteomics data. Microarray data in CEBS includes 965 hybridizations to Affymetr (...truncated)