Bioinformatics -
2 days and 8 hours ago
Publication Date: 2008 Nov 27 PMID: 19038984br/Authors: Sartor, M. A. - Leikauf, G. D. -
Medvedovic, M.br/Journal: Bioinformaticsbr/br/MOTIVATION: The elucidation of biological pathways
enriched with differentially expressed genes has become an integral part of the analysis and
interpretation of microarray data. Several statistical methods are commonly used in this context,
but the question of the optimal approach has still not been resolved. RESULTS: We present a
logistic regression based method (LRpath) for identifying predefined sets of biologically related
genes enriched with (or depleted of) differentially expressed transcripts in microarray
experiments. We functionally relate the odds of gene set membership with the significance of
differential expression, and calculate adjusted p-values as a measure of statistical significance.
The new approach is compared to Fisher's exact test and other relevant methods in a simulation
study and in the analysis of two breast cancer datasets. Overall results were concordant between
the simulation study and the experimental data analysis, and provide useful information to
investigators seeking to choose the appropriate method. LRpath displayed robust behavior and
improved statistical power compared to tested alternatives. It is applicable in experiments
involving two or more sample types, and accepts significance statistics of the investigator's
choice as input. AVAILABILITY: An R function implementing LRpath can be downloaded from
http://eh3.uc.edu/lrpath. CONTACT: Mario.medvedovic@uc.edu SUPPLEMENTARY INFORMATION: Supplementary
data are available at Bioinformatics online and at http://eh3.uc.edu/lrpath.br/br/post to: a href =
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