title: TEAK: topology enrichment analysis framework for detecting activated biological subpathways.
abstract: To mine gene expression data sets effectively, analysis frameworks need to incorporate methods that identify intergenic relationships within enriched biologically relevant subpathways. For this purpose, we developed the Topology Enrichment Analysis frameworK (TEAK). TEAK employs a novel in-house algorithm and a tailor-made Clique Percolation Method to extract linear and nonlinear KEGG subpathways, respectively. TEAK scores subpathways using the Bayesian Information Criterion for context specific data and the Kullback-Leibler divergence for case-control data. In this article, we utilized TEAK with experimental studies to analyze microarray data sets profiling stress responses in the model eukaryote Saccharomyces cerevisiae. Using a public microarray data set, we identified via TEAK linear sphingolipid metabolic subpathways activated during the yeast response to nitrogen stress, and phenotypic analyses of the corresponding deletion strains indicated previously unreported fitness defects for the dpl1Δ and lag1Δ mutants under conditions of nitrogen limitation. In addition, we studied the yeast filamentous response to nitrogen stress by profiling changes in transcript levels upon deletion of two key filamentous growth transcription factors, FLO8 and MSS11. Via TEAK we identified a nonlinear glycerophospholipid metabolism subpathway involving the SLC1 gene, which we found via mutational analysis to be required for yeast filamentous growth.
authors.affiliation: Department of Computer Science, Wayne State University, 5057 Woodward Avenue, Detroit, MI 48202, USA.
authors.forename: Thair
authors.initials: T
authors.lastname: Judeh
authors.forename: Cole
authors.initials: C
authors.lastname: Johnson
authors.forename: Anuj
authors.initials: A
authors.lastname: Kumar
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000465:Algorithms; D004398:Dyneins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D020404:Glycerophospholipids / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012984:Software; D013107:Sphingolipids / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C100940:FLO8 protein, S cerevisaie; D020404:Glycerophospholipids; C109358:MSS11 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D015534:Trans-Activators; D014157:Transcription Factors; D004398:Dyneins; C083745:SLC1 protein, S cerevisiae