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CEBS Database Now Online

By Eddy Ball
October 2006

microarray printer
Microarray printer (Photo courtesy of Steve McCaw)

NIEHS National Center for Toxicogenomics (NCT) has completed the first version of what many skeptics believed too daunting a task to ever be accomplished. On September 6, NCT launched version 2.07 of an integrated, dynamic database known as Chemical Effects in Biological Systems (CEBS), the first public repository of its kind for toxicogenomics data. CEBS developers, such as NCT Assistant Director Mike Waters, envision that the information gained through mining data in CEBS ultimately will enable health scientists and practitioners to understand and mitigate, or even prevent, diseases caused by adverse environmental exposures.

The database will prove to be an important tool for scientists researching in the field of toxicogenomics. Toxicogenomics is a scientific sub-discipline that combines the study of the nature and effects of poisons with the investigation of how our genetic make-up translates into biological functions. With improved access to more data, scientists will be able to study how and when the body's cells respond to stress, drug or toxicant, by altering the pattern of expression of genes within their chromosomes.

Even in its early stages, CEBS promises to aid researchers in identifying metabolite fingerprints and genetic signatures that may help to diagnose and define the ways in which specific chemicals, environmental exposures or stressors lead to disease. By linking damage in particular organs to alterations in serum and urine markers, researchers will strive to achieve more sensitive detection of exposure or risk factors. With CEBS, "We have an opportunity to see a landscape we've never seen before," explained Waters. "It's analogous to suddenly having the lights turned on in a room we've never seen in its entirety before, but only gotten glimpses of a small part of it, such as with a flashlight or under a street lamp."

The current version of CEBS allows researchers to access information by several analytical paths: select study workflow, study characteristics workflow, subject characteristics workflow, proteomics experiments workflow and microarray workflow. With these search capabilities researchers can view the "landscape" of data dynamically as a flow, rather than focusing exclusively on individual data gathered at single points in time.

One of the most important accomplishments of CEBS is the combination of data from microarray assessments of genetic transcriptions with traditional clinical chemistry and histopathology findings in the same database. The combination allows researchers to fully capture dose response over time, how an ongoing exposure to environmental stress modifies genetic expression and cumulatively sets the stage for disease development. The database is also multigenomic, including information for humans, rats, mice and the nematode C. elegans, a worm whose genetic makeup has been studied extensively.

Because CEBS merges different kinds of data from several sources, compiling the data presented the NCT with significant data evaluation challenges. Pulling in data from earlier research raised questions of accuracy, and different sources for the same types of data sometimes used different ascension numbering. Database developers needed to establish standard nomenclature and numerical units for searches to be effective.

The diversity of existing and pending array platforms, data acquisition methods and normalization procedures presented challenges in terms of data comparability and quality.

NCT has overcome a major barrier to developing a quality toxicogenomics database by obtaining the participation in CEBS of private sector researchers with potential proprietary interests in their information. Companies that have published data to date in CEBS include Iconix Biosciences, Johnson & Johnson, Pfizer and Sankyo. CEBS developers anticipate that more companies will agree to participate when they understand the advantages that expanded toxicogenomic research will have for them as well.

According to Waters, the job is far from over. CEBS is a powerful tool and its integration of data is impressive. However, developers admit that CEBS is hardly an intuitive research engine, and NTC will need to devote significant time and energy to user education. CEBS is a large database, with over 3,000 microarry hybridizations, 75 two-dimensional gel images, and traditional findings from over 600 animals, but it is still in its early stages. Frequent visitors to CEBS should be seeing new versions coming online in the future, as upgrades are developed to enhance loading capabilities, integrate CEBS with other data resources and expand the user base.

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