GEN3VA: aggregation and analysis of gene expression signatures from related studies.

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 .

Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd.

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.