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. 2016 Nov 15;17(1):461.
doi: 10.1186/s12859-016-1321-1.

GEN3VA: Aggregation and Analysis of Gene Expression Signatures From Related Studies

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Free PMC article

GEN3VA: Aggregation and Analysis of Gene Expression Signatures From Related Studies

Gregory W Gundersen et al. BMC Bioinformatics. .
Free PMC article

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 .

Keywords: Data mining; Interactive reports; Microarrays; Systems Biology.

Figures

Fig. 1
Fig. 1
Screenshot from the GEN3VA landing page
Fig. 2
Fig. 2
Screenshot from the 3D PCA analysis of the aging signature collection
Fig. 3
Fig. 3
Screenshot from the genes heatmap of the aging signature collection showing the top 10 most up- and down-regulated genes across all studies
Fig. 4
Fig. 4
Screenshot from the enrichment analysis heatmap of the aging signature collection using the ENCODE library with a filter for the top 20 most consistently enriched terms
Fig. 5
Fig. 5
Screenshot from the L1000 drug-induced signatures enrichment analysis heatmap of the aging signature collection. Blue spots are reversers of the expression signatures, and red spots are mimickers. The filter is set to the overall top 20 most consistent enriched drugs
Fig. 6
Fig. 6
Screenshot from the 3D PCA analysis of the dexamethasone signature collection
Fig. 7
Fig. 7
Screenshot from the genes heatmap of the dexamethasone signature collection showing the top 10 most up- and down-regulated genes across all studies
Fig. 8
Fig. 8
Screenshot from the enrichment analysis heatmap of the dexamethasone signature collection using the ENCODE library with a filter for the top 20 most consistently enriched terms
Fig. 9
Fig. 9
Screenshot from the L1000 drug-induced signatures enrichment analysis heatmap of the dexamethasone signature collection. Blue spots are reversers of the expression signatures, and red spots are mimickers. The filter is set to the overall top 50 most consistent enriched drugs
Fig. 10
Fig. 10
Docking of ketorolac and dexamethasone to the GR pocket. a zinc2279 (R)-ketorolac; b zinc11012 (S)-ketorolac. The white ribbon is the 1m2z structure, green stick is the ligand dexamethasone in crystal. Cyan stick is the ligand ketorolac
Fig. 11
Fig. 11
Docking of thalidomide and dexamethasone to the GR pocket. a (S)-thalidomide; b (R)-thalidomide

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