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Open Access Open Badges Methodology article

Nonparametric tests for differential gene expression and interaction effects in multi-factorial microarray experiments

Xin Gao1* and Peter XK Song2

Author Affiliations

1 Department of Mathematics and Statistics, York University, 4700 Keele Street, Toronto, ON M3J 1P3, Canada

2 Department of Statistics and Actuarial Science, University of Waterloo, 200 University Ave. W., Waterloo, ON N2L 3G1, Canada

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BMC Bioinformatics 2005, 6:186  doi:10.1186/1471-2105-6-186

Published: 21 July 2005



Numerous nonparametric approaches have been proposed in literature to detect differential gene expression in the setting of two user-defined groups. However, there is a lack of nonparametric procedures to analyze microarray data with multiple factors attributing to the gene expression. Furthermore, incorporating interaction effects in the analysis of microarray data has long been of great interest to biological scientists, little of which has been investigated in the nonparametric framework.


In this paper, we propose a set of nonparametric tests to detect treatment effects, clinical covariate effects, and interaction effects for multifactorial microarray data. When the distribution of expression data is skewed or heavy-tailed, the rank tests are substantially more powerful than the competing parametric F tests. On the other hand, in the case of light or medium-tailed distributions, the rank tests appear to be marginally less powerful than the parametric competitors.


The proposed rank tests enable us to detect differential gene expression and establish interaction effects for microarray data with various non-normally distributed expression measurements across genome. In the presence of outliers, they are advantageous alternative approaches to the existing parametric F tests due to the robustness feature.