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Open Access Highly Accessed Methodology article

A statistical method to incorporate biological knowledge for generating testable novel gene regulatory interactions from microarray experiments

Peter Larsen1, Eyad Almasri2, Guanrao Chen3 and Yang Dai2*

Author Affiliations

1 Core Genomics Laboratory at University of Illinois at Chicago, 845 West Taylor Street Chicago, IL 60607, USA

2 Department of Bioengineering (MC063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607, USA

3 Department of Computer Science, University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607, USA

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BMC Bioinformatics 2007, 8:317  doi:10.1186/1471-2105-8-317

Published: 29 August 2007

Abstract

Background

The incorporation of prior biological knowledge in the analysis of microarray data has become important in the reconstruction of transcription regulatory networks in a cell. Most of the current research has been focused on the integration of multiple sets of microarray data as well as curated databases for a genome scale reconstruction. However, individual researchers are more interested in the extraction of most useful information from the data of their hypothesis-driven microarray experiments. How to compile the prior biological knowledge from literature to facilitate new hypothesis generation from a microarray experiment is the focus of this work. We propose a novel method based on the statistical analysis of reported gene interactions in PubMed literature.

Results

Using Gene Ontology (GO) Molecular Function annotation for reported gene regulatory interactions in PubMed literature, a statistical analysis method was proposed for the derivation of a likelihood of interaction (LOI) score for a pair of genes. The LOI-score and the Pearson correlation coefficient of gene profiles were utilized to check if a pair of query genes would be in the above specified interaction. The method was validated in the analysis of two gene sets formed from the yeast Saccharomyces cerevisiae cell cycle microarray data. It was found that high percentage of identified interactions shares GO Biological Process annotations (39.5% for a 102 interaction enriched gene set and 23.0% for a larger 999 cyclically expressed gene set).

Conclusion

This method can uncover novel biologically relevant gene interactions. With stringent confidence levels, small interaction networks can be identified for further establishment of a hypothesis testable by biological experiment. This procedure is computationally inexpensive and can be used as a preprocessing procedure for screening potential biologically relevant gene pairs subject to the analysis with sophisticated statistical methods.