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Open Access Highly Accessed Methodology article

Discovering biological connections between experimental conditions based on common patterns of differential gene expression

Adam C Gower1, Avrum Spira12 and Marc E Lenburg12*

Author Affiliations

1 Bioinformatics Program, Boston University, 44 Cummington Street, Boston, Massachusetts, 02215, USA

2 Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Evans 631, Boston, Massachusetts, 02118, USA

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BMC Bioinformatics 2011, 12:381  doi:10.1186/1471-2105-12-381

Published: 27 September 2011

Abstract

Background

Identifying similarities between patterns of differential gene expression provides an opportunity to identify similarities between the experimental and biological conditions that give rise to these gene expression alterations. The growing volume of gene expression data in open data repositories such as the NCBI Gene Expression Omnibus (GEO) presents an opportunity to identify these gene expression similarities on a large scale across a diverse collection of datasets. We have developed a fast, pattern-based computational approach, named openSESAME (Search of Expression Signatures Across Many Experiments), that identifies datasets enriched in samples that display coordinate differential expression of a query signature. Importantly, openSESAME performs this search without prior knowledge of the phenotypic or experimental groups in the datasets being searched. This allows openSESAME to identify perturbations of gene expression that are due to phenotypic attributes that may not have been described in the sample annotation included in the repository.

To demonstrate the utility of openSESAME, we used gene expression signatures of two biological perturbations to query a set of 75,164 human expression profiles that were generated using Affymetrix microarrays and deposited in GEO. The first query, using a signature of estradiol treatment, identified experiments in which estrogen signaling was perturbed and also identified differences in estrogen signaling between estrogen receptor-positive and -negative breast cancers. The second query, which used a signature of silencing of the transcription factor p63 (a key regulator of epidermal differentiation), identified datasets related to stratified squamous epithelia or epidermal diseases such as melanoma.

Conclusions

openSESAME is a tool for leveraging the growing body of publicly available microarray data to discover relationships between different biological states based on common patterns of differential gene expression. These relationships may serve to generate hypotheses about the causes and consequences of specific patterns of observed differential gene expression. To encourage others to explore the utility of this approach, we have made a website for performing openSESAME queries freely available at http://opensesame.bu.edu webcite.