Bioinformatics Advance Access originally published online on July 28, 2006
Bioinformatics 2006 22(19):2373-2380; doi:10.1093/bioinformatics/btl401
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A multivariate approach for integrating genome-wide expression data and biological knowledge
1 Department of Cardiology 300 Longwood Avenue, Boston, MA 02115, USA
2 Informatics Program, Children's Hospital Boston 300 Longwood Avenue, Boston, MA 02115, USA
3 Harvard-Partners Center for Genetics and Genomics, 77 Avenue Louis Pasteur Boston, MA 02115, USA
*To whom correspondence should be addressed.
Motivation: Several statistical methods that combine analysis of differential gene expression with biological knowledge databases have been proposed for a more rapid interpretation of expression data. However, most such methods are based on a series of univariate statistical tests and do not properly account for the complex structure of gene interactions.
Results: We present a simple yet effective multivariate statistical procedure for assessing the correlation between a subspace defined by a group of genes and a binary phenotype. A subspace is deemed significant if the samples corresponding to different phenotypes are well separated in that subspace. The separation is measured using Hotelling's T2 statistic, which captures the covariance structure of the subspace. When the dimension of the subspace is larger than that of the sample space, we project the original data to a smaller orthonormal subspace. We use this method to search through functional pathway subspaces defined by Reactome, KEGG, BioCarta and Gene Ontology. To demonstrate its performance, we apply this method to the data from two published studies, and visualize the results in the principal component space.
Contact: peter_park{at}harvard.edu
Received on February 9, 2006; revised on June 27, 2006; accepted on July 18, 2006
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