title: A biological evaluation of six gene set analysis methods for identification of differentially expressed pathways in microarray data.
abstract: Gene-set analysis of microarray data evaluates biological pathways, or gene sets, for their differential expression by a phenotype of interest. In contrast to the analysis of individual genes, gene-set analysis utilizes existing biological knowledge of genes and their pathways in assessing differential expression. This paper evaluates the biological performance of five gene-set analysis methods testing "self-contained null hypotheses" via subject sampling, along with the most popular gene-set analysis method, Gene Set Enrichment Analysis (GSEA). We use three real microarray analyses in which differentially expressed gene sets are predictable biologically from the phenotype. Two types of gene sets are considered for this empirical evaluation: one type contains "truly positive" sets that should be identified as differentially expressed; and the other type contains "truly negative" sets that should not be identified as differentially expressed. Our evaluation suggests advantages of SAM-GS, Global, and ANCOVA Global methods over GSEA and the other two methods.
authors.affiliation: School of Public Health, University of Alberta, 13-106 Clinical Sciences Building, Edmonton, AB, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Dinu
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Adeniyi J
authors.initials: AJ
authors.lastname: Adewale
authors.forename: Gian S
authors.initials: GS
authors.lastname: Jhangri
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: Gunilla
authors.initials: G
authors.lastname: Einecke
authors.forename: Konrad
authors.initials: K
authors.lastname: Famulsky
authors.forename: Philip
authors.initials: P
authors.lastname: Halloran
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui