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BMC Bioinformatics

, 5:209

First Online: 30 December 2004Received: 15 April 2004Accepted: 30 December 2004

Abstract

BackgroundTwo or more factor mixed factorial experiments are becoming increasingly common in microarray data analysis. In this case study, the two factors are presence Patients with Alzheimer-s disease or absence Control of the disease, and brain regions including olfactory bulb OB or cerebellum CER. In the design considered in this manuscript, OB and CER are repeated measurements from the same subject and, hence, are correlated. It is critical to identify sources of variability in the analysis of oligonucleotide array experiments with repeated measures and correlations among data points have to be considered. In addition, multiple testing problems are more complicated in experiments with multi-level treatments or treatment combinations.

ResultsIn this study we adopted a linear mixed model to analyze oligonucleotide array experiments with repeated measures. We first construct a generalized F test to select differentially expressed genes. The Benjamini and Hochberg BH procedure of controlling false discovery rate FDR at 5% was applied to the P values of the generalized F test. For those genes with significant generalized F test, we then categorize them based on whether the interaction terms were significant or not at the α-level αnew= 0.0033 determined by the FDR procedure. Since simple effects may be examined for the genes with significant interaction effect, we adopt the protected Fisher-s least significant difference test LSD procedure at the level of αnewto control the family-wise error rate FWER for each gene examined.

ConclusionsA linear mixed model is appropriate for analysis of oligonucleotide array experiments with repeated measures. We constructed a generalized F test to select differentially expressed genes, and then applied a specific sequence of tests to identify factorial effects. This sequence of tests applied was designed to control for gene based FWER.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-5-209 contains supplementary material, which is available to authorized users.

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Author: Hao Li - Constance L Wood - Thomas V Getchell - Marilyn L Getchell - Arnold J Stromberg

Source: https://link.springer.com/



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