title: GEN3VA: aggregation and analysis of gene expression signatures from related studies.
abstract: BACKGROUND
  Genome-wide gene expression profiling of mammalian cells is becoming a staple of many published biomedical and biological research studies. Such data is deposited into data repositories such as the Gene Expression Omnibus (GEO) for potential reuse. However, these repositories currently do not provide simple interfaces to systematically analyze collections of related studies.
  
  
  RESULTS
  Here we present GENE Expression and Enrichment Vector Analyzer (GEN3VA), a web-based system that enables the integrative analysis of aggregated collections of tagged gene expression signatures identified and extracted from GEO. Each tagged collection of signatures is presented in a report that consists of heatmaps of the differentially expressed genes; principal component analysis of all signatures; enrichment analysis with several gene set libraries across all signatures, which we term enrichment vector analysis; and global mapping of small molecules that are predicted to reverse or mimic each signature in the aggregate. We demonstrate how GEN3VA can be used to identify common molecular mechanisms of aging by analyzing tagged signatures from 244 studies that compared young vs. old tissues in mammalian systems. In a second case study, we collected 86 signatures from treatment of human cells with dexamethasone, a glucocorticoid receptor (GR) agonist. Our analysis confirms consensus GR target genes and predicts potential drug mimickers.
  
  
  CONCLUSIONS
  GEN3VA can be used to identify, aggregate, and analyze themed collections of gene expression signatures from diverse but related studies. Such integrative analyses can be used to address concerns about data reproducibility, confirm results across labs, and discover new collective knowledge by data reuse. GEN3VA is an open-source web-based system that is freely available at: http://amp.pharm.mssm.edu/gen3va .
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Gundersen
authors.affiliation: Fluid Physics and Transport Processes Branch, NASA Glenn Research Center, 21000 Brookpark Rd, Cleveland, OH, 44135, USA.|Center for Space Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Jagodnik
authors.affiliation: , Daylesford, The Fairway, Weybridge, Surrey, KT13 0RZ, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Woodland
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Fernandez
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sani
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Anders B
authors.initials: AB
authors.lastname: Dohlman
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Peter Man-Un
authors.initials: PM
authors.lastname: Ung
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Monteiro
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA.
authors.forename: Avner
authors.initials: A
authors.lastname: Schlessinger
authors.affiliation: Department of Pharmacological Sciences, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA. avi.maayan@mssm.edu.|Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY, 10029, USA. avi.maayan@mssm.edu.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015203:Reproducibility of Results; D012984:Software; D059467:Transcriptome
chemical_list: D003907:Dexamethasone
keywords: Data mining; Interactive reports; Microarrays; Systems Biology