Absolute enrichment: gene set enrichment analysis for homeostatic systems

The Gene Set Enrichment Analysis (GSEA) identifies sets of genes that are differentially regulated in one direction. Many homeostatic systems will include one limb that is upregulated in response to a downregulation of another limb and vice versa. Such patterns are poorly captured by the standard formulation of GSEA. We describe a technique to identify groups of genes (which sometimes can be pathways) that include both up- and down-regulated components. This approach lends insights into the feedback mechanisms that may operate, especially when integrated with protein interaction databases.

[1]  A. Aszódi,et al.  Mouse models for extracellular matrix diseases , 1998, Journal of Molecular Medicine.

[2]  R. Derynck,et al.  TGF-β signaling in cancer – a double-edged sword , 2001 .

[3]  R. Derynck,et al.  TGF-beta signaling in cancer--a double-edged sword. , 2001, Trends in cell biology.

[4]  Alex E. Lash,et al.  Gene Expression Omnibus: NCBI gene expression and hybridization array data repository , 2002, Nucleic Acids Res..

[5]  Brad T. Sherman,et al.  DAVID: Database for Annotation, Visualization, and Integrated Discovery , 2003, Genome Biology.

[6]  M. Hofker.  Faculty Opinions recommendation of PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. , 2003 .

[7]  S. Namkoong,et al.  Targeted cellular process profiling approach for uterine leiomyoma using cDNA microarray, proteomics and gene ontology analysis , 2003, International journal of experimental pathology.

[8]  Douglas A. Hosack,et al.  Identifying biological themes within lists of genes with EASE , 2003, Genome Biology.

[9]  Yusuke Nakamura,et al.  Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer , 2004, Cancer Research.

[10]  Seon-Young Kim,et al.  PAGE: Parametric Analysis of Gene Set Enrichment , 2005, BMC Bioinform..

[11]  J. Segars,et al.  Gene expression studies in leiomyomata: new directions for research. , 2004, Seminars in reproductive medicine.

[12]  J. Gregg,et al.  Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis. , 2004, Fertility and sterility.

[13]  P. Meltzer,et al.  Gene expression profiling of human sarcomas: insights into sarcoma biology. , 2005, Cancer research.

[14]  Dennis B. Troup,et al.  NCBI GEO: mining millions of expression profiles—database and tools , 2004, Nucleic Acids Res..

[15]  Robert J. Marinelli,et al.  The gene expression profile of extraskeletal myxoid chondrosarcoma , 2005, The Journal of pathology.

[16]  L. Aaltonen,et al.  7q deletion mapping and expression profiling in uterine fibroids , 2005, Oncogene.

[17]  Jane Lomax,et al.  Get ready to GO! A biologist's guide to the Gene Ontology , 2005, Briefings Bioinform..

[18]  Kaisheng Chen,et al.  In silico gene function prediction using ontology-based pattern identification , 2005, Bioinform..

[19]  G. Kong,et al.  Profiling of differentially expressed genes in human uterine leiomyomas , 2004, International Journal of Gynecologic Cancer.

[20]  C. Walker,et al.  Uterine Fibroids: The Elephant in the Room , 2005, Science.