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First published online on September 26, 2003.
Copyright © 2003 by The Physiological Society
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Received June 25, 2003
Revised August 1, 2003
Accepted after revision September 25, 2003

High throughput gene expression profiling: A molecular approach to integrative physiology

Mingyu Liang1*, Allen W. Cowley, Jr.1, and Andrew S. Greene1

1 Medical College of Wisconsin

* To whom correspondence should be addressed. E-mail: mliang{at}mcw.edu.

Integrative physiology emphasizes the importance of understanding multiple pathways with overlapping, complementary, or opposing effects and their interactions in the context of intact organisms. The DNA microarray technology, the most commonly used method for high-throughput gene expression profiling, has been touted as an integrative tool that provides insights into regulatory pathways. However, the physiology community has been slow in acceptance of these techniques because of early failure in generating useful data and the lack of a cohesive theoretical framework in which experiments can be analyzed. With recent advance in both technology and analysis, we propose a concept of multi-dimensional integration of physiology that incorporates data generated by DNA microarray and other functional, genomic, and proteomic approaches to achieve a truly integrative understanding of physiology. Analysis of several studies performed in simpler organisms or in mammalian model animals supports the feasibility of such multi-dimensional integration and demonstrates the power of DNA microarray as an indispensable molecular tool for such integration. Evaluation of DNA microarray techniques indicates that these techniques, despite limitations, have advanced to a point where the question-driven profiling research has become a feasible complement to the conventional, hypothesis-driven research. With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions.




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