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Open Access Highly Accessed Methodology article

A factor model to analyze heterogeneity in gene expression

Yuna Blum123*, Guillaume Le Mignon12, Sandrine Lagarrigue12 and David Causeur3

Author Affiliations

1 Agrocampus Ouest, UMR598, Animal Genetics, 35000 Rennes, France

2 INRA, UMR598, Animal Genetics, 35000 Rennes, France

3 Agrocampus Ouest, Applied Mathematics Department, 35000 Rennes, France

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BMC Bioinformatics 2010, 11:368  doi:10.1186/1471-2105-11-368

Published: 2 July 2010

Abstract

Background

Microarray technology allows the simultaneous analysis of thousands of genes within a single experiment. Significance analyses of transcriptomic data ignore the gene dependence structure. This leads to correlation among test statistics which affects a strong control of the false discovery proportion. A recent method called FAMT allows capturing the gene dependence into factors in order to improve high-dimensional multiple testing procedures. In the subsequent analyses aiming at a functional characterization of the differentially expressed genes, our study shows how these factors can be used both to identify the components of expression heterogeneity and to give more insight into the underlying biological processes.

Results

The use of factors to characterize simple patterns of heterogeneity is first demonstrated on illustrative gene expression data sets. An expression data set primarily generated to map QTL for fatness in chickens is then analyzed. Contrarily to the analysis based on the raw data, a relevant functional information about a QTL region is revealed by factor-adjustment of the gene expressions. Additionally, the interpretation of the independent factors regarding known information about both experimental design and genes shows that some factors may have different and complex origins.

Conclusions

As biological information and technological biases are identified in what was before simply considered as statistical noise, analyzing heterogeneity in gene expression yields a new point of view on transcriptomic data.