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Free keywords:
drug discovery; functional genomics; microarray; bioinformatics; data integration; database; systems biology
Abstract:
Understanding individual response to a drug—what determines its efficacy and tolerability—is the major bottleneck in
current drug development and clinical trials. Intracellular response and metabolism, for example through cytochrome P-
450 enzymes, may either enhance or decrease the effect of different drugs, dependent on the genetic variant. Microarrays
offer the potential to screen the genetic composition of the individual patient. However, experiments are “noisy” and
must be accompanied by solid and robust data analysis. Furthermore, recent research aims at the combination of highthroughput data with methods of mathematical modeling, enabling problem-oriented assistance in the drug discovery
process. This article will discuss state-of-the-art DNA array technology platforms and the basic elements of data analysis
and bioinformatics research in drug discovery. Enhancing single-gene analysis, we will present a new method for interpreting
gene expression changes in the context of entire pathways. Furthermore, we will introduce the concept of systems
biology as a new paradigm for drug development and highlight our recent research—the development of a modeling
and simulation platform for biomedical applications. We discuss the potentials of systems biology for modeling the
drug response of the individual patient.
