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Physiol. Genomics (October 22, 2002). doi:10.1152/physiolgenomics.00024.2002
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Articles in PresS, published online ahead of print October 22, 2002
Physiol Genomics, 10.1152/physiolgenomics.00024.2002
Submitted on March 6, 2002
Accepted on October 16, 2002

Improved Significance Test for DNA Microarray Data: Temporal modulation of endothelial gene expression by shear stress

Yihua Zhao1, Benjamin P. C Chen1, Hui Miao1, Suli Yuan1, Yi-Shuan Li1, Yingli Hu1, David M Rocke2, and Shu Chien1*

1 Department of Bioengineering and the Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, California, USA
2 Department of Applied Science, University of California, Davis, Davis, California, USA

* To whom correspondence should be addressed. E-mail: schien{at}bioeng.ucsd.edu.

Statistical methods for identifying differentially expressed genes from microarray data are evolving. We developed a test for the statistical significance of differential expression as a function of time. When applied to microarray data obtained from endothelial cells exposed to shearing for different durations, the new multi-group test (G-test) identified three times as many genes as the one-way ANOVA at the same significance level. Using simulated data, we showed that this increase in sensitivity was achieved without scarifying specificity. Several genes known to respond to shear stress by Northern blotting were identified by the G-test at P <= 0.01 (but not by ANOVA), with similar temporal patterns. The validity and utility of the G-test were further supported by the examination of a few more example genes in relation to the present knowledge of their regulatory mechanisms. This new significance test may have broad application for the analysis of gene-expression studies, and in fact to other biological studies in general.




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