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METABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Extracting Global System Dynamics of Corticosteroid Genomic Effects in Rat Liver

Departments of Biomedical Engineering (E.Y., I.P.A.) and Chemical and Biochemical Engineering (I.P.A.), Rutgers University, Piscataway, New Jersey; Departments of Biological Sciences (R.R.A., D.C.D.) and Pharmaceutical Sciences (R.R.A., D.C.D., W.J.J.), SUNY Buffalo, New York; and New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York (R.R.A., W.J.J.)

One of the challenges in constructing biological models involves resolving meaningful data patterns from which the mathematical models will be generated. For models that describe the change of mRNA in response to drug administration, questions exist whether the correct genes have been selected given the myriad transcriptional effects that may occur. Oftentimes, different algorithms will select or cluster different groups of genes from the same data set. A new approach was developed that focuses on identifying the underlying global dynamics of the system instead of selecting individual genes. The procedure was applied to microarray genomic data obtained from rat liver after a large single dose of methylprednisolone in 52 adrenalectomized rats. Twelve clusters of at least 30 genes each were selected, reflecting the major changes over time. This method along with isolating the underlying dynamics of the system also extracts and clusters the genes that make up this global dynamic for further analysis as to the contributions of specific mechanisms affected by the drug.

Address correspondence to: Dr. Ioannis P. Androulakis, Department of Biomedical Engineering, Rutgers University; 599 Taylor Rd., Piscataway, NJ 08544. E-mail: yannis{at}rci.rutgers.edu