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Open Access Highly Accessed Methodology article

PAGE: Parametric Analysis of Gene Set Enrichment

Seon-Young Kim2 and David J Volsky13

Author Affiliations

1 Molecular Virology Division, St. Luke's-Roosevelt Hospital Center and Columbia University, New York, NY 10019, USA

2 Human Genomics Laboratory, Genome Research Center, Korea Research, Institute of Biosciences and Biotechnology 52 Eoeun-dong Yuseong-gu, Daejon, 305-333, Korea

3 Molecular Virology Division, St. Luke's-Roosevelt Hospital Center 432 West 58th, Street Antenucci Building, Room 709 New York, NY 10019, USA

BMC Bioinformatics 2005, 6:144  doi:10.1186/1471-2105-6-144

Published: 8 June 2005

Abstract

Background

Gene set enrichment analysis (GSEA) is a microarray data analysis method that uses predefined gene sets and ranks of genes to identify significant biological changes in microarray data sets. GSEA is especially useful when gene expression changes in a given microarray data set is minimal or moderate.

Results

We developed a modified gene set enrichment analysis method based on a parametric statistical analysis model. Compared with GSEA, the parametric analysis of gene set enrichment (PAGE) detected a larger number of significantly altered gene sets and their p-values were lower than the corresponding p-values calculated by GSEA. Because PAGE uses normal distribution for statistical inference, it requires less computation than GSEA, which needs repeated computation of the permutated data set. PAGE was able to detect significantly changed gene sets from microarray data irrespective of different Affymetrix probe level analysis methods or different microarray platforms. Comparison of two aged muscle microarray data sets at gene set level using PAGE revealed common biological themes better than comparison at individual gene level.

Conclusion

PAGE was statistically more sensitive and required much less computational effort than GSEA, it could identify significantly changed biological themes from microarray data irrespective of analysis methods or microarray platforms, and it was useful in comparison of multiple microarray data sets. We offer PAGE as a useful microarray analysis method.