An enhanced quantile approach for assessing differential gene expressions

Due to the small number of replicates in typical gene microarray experiments, the performance of statistical inference is often unsatisfactory without some form of information-sharing across genes. In this article, we propose an enhanced quantile rank score test (EQRS) for detecting differential expression in GeneChip studies by analyzing the quantiles of gene intensity distributions through probe-level measurements. A measure of sign correlation, delta, plays an important role in the rank score tests. By sharing information across genes, we develop a calibrated estimate of delta, which reduces the variability at small sample sizes. We compare the EQRS test with four other approaches for determining differential expression: the gene-specific quantile rank score test, the quantile rank score test assuming a common delta, a modified t-test using summarized probe-set-level intensities, and the Mack-Skillings rank test on probe-level data. The proposed EQRS is shown to be favorable for preserving false discovery rates and for being robust against outlying arrays. In addition, we demonstrate the merits of the proposed approach using a GeneChip study comparing gene expression in the livers of mice exposed to chronic intermittent hypoxia and of those exposed to intermittent room air.