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Oxford University Press, Bioinformatics, 3(24), p. 374-382, 2008

DOI: 10.1093/bioinformatics/btm620

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A comparison of meta-analysis methods for detecting differentially expressed genes in microarray experiments

Journal article published in 2008 by Fangxin Hong, Rainer Breitling ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Motivation: The proliferation of public data repositories creates a need for meta-analysis methods to efficiently evaluate, integrate and validate related datasets produced by independent groups. A t-based approach has been proposed to integrate effect size from multiple studies by modeling both intra- and between-study variation. Recently, a non-parametric 'rank product' method, which is derived based on biological reasoning of fold-change criteria, has been applied to directly combine multiple datasets into one meta study. Fisher's Inverse ??2 method, which only depends on P-values from individual analyses of each dataset, has been used in a couple of medical studies. While these methods address the question from different angles, it is not clear how they compare with each other. Results: We comparatively evaluate the three methods; t-based hierarchical modeling, rank products and Fisher's Inverse ??2 test with P-values from either the t-based or the rank product method. A simulation study shows that the rank product method, in general, has higher sensitivity and selectivity than the t-based method in both individual and meta-analysis, especially in the setting of small sample size and/or large between-study variation. Not surprisingly, Fisher's ??2 method highly depends on the method used in the individual analysis. Application to real datasets demonstrates that meta-analysis achieves more reliable identification than an individual analysis, and rank products are more robust in gene ranking, which leads to a much higher reproducibility among independent studies. Though t-based meta-analysis greatly improves over the individual analysis, it suffers from a potentially large amount of false positives when P-values serve as threshold. We conclude that careful meta-analysis is a powerful tool for integrating multiple array studies. ?? The Author 2008. Published by Oxford University Press. All rights reserved.