Meta-analysis of gene expression microarrays with missing replicates

Fan Shi, Gad Abraham, Christopher Leckie, Izhak Haviv, Adam Kowalczyk

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Many different microarray experiments are publicly available today. It is natural to ask whether different experiments for the same phenotypic conditions can be combined using meta-analysis, in order to increase the overall sample size. However, some genes are not measured in all experiments, hence they cannot be included or their statistical significance cannot be appropriately estimated in traditional meta-analysis. Nonetheless, these genes, which we refer to as incomplete genes, may also be informative and useful.Results: We propose a meta-analysis framework, called "Incomplete Gene Meta-analysis", which can include incomplete genes by imputing the significance of missing replicates, and computing a meta-score for every gene across all datasets. We demonstrate that the incomplete genes are worthy of being included and our method is able to appropriately estimate their significance in two groups of experiments. We first apply the Incomplete Gene Meta-analysis and several comparable methods to five breast cancer datasets with an identical set of probes. We simulate incomplete genes by randomly removing a subset of probes from each dataset and demonstrate that our method consistently outperforms two other methods in terms of their false discovery rate. We also apply the methods to three gastric cancer datasets for the purpose of discriminating diffuse and intestinal subtypes.Conclusions: Meta-analysis is an effective approach that identifies more robust sets of differentially expressed genes from multiple studies. The incomplete genes that mainly arise from the use of different platforms may also have statistical and biological importance but are ignored or are not appropriately involved by previous studies. Our Incomplete Gene Meta-analysis is able to incorporate the incomplete genes by estimating their significance. The results on both breast and gastric cancer datasets suggest that the highly ranked genes and associated GO terms produced by our method are more significant and biologically meaningful according to the previous literature.

Original languageEnglish
Article number84
JournalBMC Bioinformatics
Volume12
DOIs
StatePublished - 24 Mar 2011
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Australian Research Council, and by the NICTA Victorian Research Laboratory. NICTA is funded by the Australian Government as represented by the Department of Broadband, Communications and the Digital Economy and the Australian Research Council through the ICT Center of Excellence program.

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