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Complementary Roles for Toxicologic Pathology and Mathematics in Toxicogenomics, With Special Reference to Data Interpretation and Oscillatory Dynamics

Aventis Pharmaceuticals, Bridgewater, New Jersey, USA, kevin.morgan{at}aventis.com

Michael Pino

Aventis Pharmaceuticals, Bridgewater, New Jersey, USA

Lynn M. Crosby

GeneExpressions, Raleigh, North Carolina, USA

Min Wang

Aventis Pharmaceuticals, Bridgewater, New Jersey, USA

Timothy C. Elston

Department of Mathematics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA

Zaid Jayyosi

Aventis Pharmaceuticals, Bridgewater, New Jersey, USA

Marc Bonnefoi

Aventis Pharmaceuticals, Bridgewater, New Jersey, USA

Gary Boorman

NIEHS, Research Triangle Park, North Carolina, USA

Toxicogenomics is an emerging multidisciplinary science that will profoundly impact the practice of toxicology. New generations of biologists, using evolving toxicogenomics tools, will generate massive data sets in need of interpretation. Mathematical tools are necessary to cluster and otherwise find meaningful structure in such data. The linking of this structure to gene functions and disease processes, and finally the generation of useful data interpretation remains a significant challenge. The training and background of pathologists make them ideally suited to contribute to the field of toxicogenomics, from experimental design to data interpretation. Toxicologic pathology, a discipline based on pattern recognition, requires familiarity with the dynamics of disease processes and interactions between organs, tissues, and cell populations. Optimal involvement of toxicologic pathologists in toxicogenomics requires that they communicate effectively with the many other scientists critical for the effective application of this complex discipline to societal problems. As noted by Petricoin III et al (Nature Genetics 32, 474-479, 2002), cooperation among regulators, sponsors and experts will be essential for realizing the potential of microarrays for public health. Following a brief introduction to the role of mathematics in toxicogenomics, "data interpretation" from the perspective of a pathologist is briefly discussed. Based on oscillatory behavior in the liver, the importance of an understanding of mathematics is addressed, and an approach to learning mathematics "later in life" is provided. An understanding of pathology by mathematicians involved in toxicogenomics is equally critical, as both mathematics and pathology are essential for transforming toxicogenomics data sets into useful knowledge.

Key Words: Toxicogenomics • differential gene expression interpretation • pathology • gene expression dynamics • interdisciplinary communication • learning mathematics.

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