NCBI GEO: archive for gene expression and epigenomics data sets: 23-year update.

The Gene Expression Omnibus (GEO) is an international public repository that archives gene expression and epigenomics data sets generated by next-generation sequencing and microarray technologies. Data are typically submitted to GEO by researchers in compliance with widespread journal and funder mandates to make generated data publicly accessible. The resource handles raw data files, processed data files and descriptive metadata for over 200 000 studies and 6.5 million samples, all of which are indexed, searchable and downloadable. Additionally, GEO offers web-based tools that facilitate analysis and visualization of differential gene expression. This article presents the current status and recent advancements in GEO, including the generation of consistently computed gene expression count matrices for thousands of RNA-seq studies, and new interactive graphical plots in GEO2R that help users identify differentially expressed genes and assess data set quality. The GEO repository is built and maintained by the National Center for Biotechnology Information (NCBI), a division of the National Library of Medicine (NLM), and is publicly accessible at https://www.ncbi.nlm.nih.gov/geo/.

NCBI GEO: archive for functional genomics data sets--update.

The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.

NCBI GEO: archive for functional genomics data sets--10 years on.

A decade ago, the Gene Expression Omnibus (GEO) database was established at the National Center for Biotechnology Information (NCBI). The original objective of GEO was to serve as a public repository for high-throughput gene expression data generated mostly by microarray technology. However, the research community quickly applied microarrays to non-gene-expression studies, including examination of genome copy number variation and genome-wide profiling of DNA-binding proteins. Because the GEO database was designed with a flexible structure, it was possible to quickly adapt the repository to store these data types. More recently, as the microarray community switches to next-generation sequencing technologies, GEO has again adapted to host these data sets. Today, GEO stores over 20,000 microarray- and sequence-based functional genomics studies, and continues to handle the majority of direct high-throughput data submissions from the research community. Multiple mechanisms are provided to help users effectively search, browse, download and visualize the data at the level of individual genes or entire studies. This paper describes recent database enhancements, including new search and data representation tools, as well as a brief review of how the community uses GEO data. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/.

NCBI GEO: archive for high-throughput functional genomic data.

The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest public repository for high-throughput gene expression data. Additionally, GEO hosts other categories of high-throughput functional genomic data, including those that examine genome copy number variations, chromatin structure, methylation status and transcription factor binding. These data are generated by the research community using high-throughput technologies like microarrays and, more recently, next-generation sequencing. The database has a flexible infrastructure that can capture fully annotated raw and processed data, enabling compliance with major community-derived scientific reporting standards such as 'Minimum Information About a Microarray Experiment' (MIAME). In addition to serving as a centralized data storage hub, GEO offers many tools and features that allow users to effectively explore, analyze and download expression data from both gene-centric and experiment-centric perspectives. This article summarizes the GEO repository structure, content and operating procedures, as well as recently introduced data mining features. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/.

NCBI GEO: mining tens of millions of expression profiles--database and tools update.

The Gene Expression Omnibus (GEO) repository at the National Center for Biotechnology Information (NCBI) archives and freely disseminates microarray and other forms of high-throughput data generated by the scientific community. The database has a minimum information about a microarray experiment (MIAME)-compliant infrastructure that captures fully annotated raw and processed data. Several data deposit options and formats are supported, including web forms, spreadsheets, XML and Simple Omnibus Format in Text (SOFT). In addition to data storage, a collection of user-friendly web-based interfaces and applications are available to help users effectively explore, visualize and download the thousands of experiments and tens of millions of gene expression patterns stored in GEO. This paper provides a summary of the GEO database structure and user facilities, and describes recent enhancements to database design, performance, submission format options, data query and retrieval utilities. GEO is accessible at http://www.ncbi.nlm.nih.gov/geo/

Cytogenetic characterization and gene expression profiling in the rat reflux-induced esophageal tumor model.

OBJECTIVES: The reasons for the increasing incidence of esophageal adenocarcinoma are not clear. A causal relation between gastroesophageal reflux disease and esophageal adenocarcinoma has been suggested. Support for this comes from the development of esophageal adenocarcinoma in the rat reflux model. However, to date, no systematic characterization of the tumors derived from this model has been reported. METHODS: We induced biliary reflux by creating esophagojejunal anastomoses in 12 Sprague-Dawley rats. The experiment was terminated at 9 months, and rat esophagi were harvested for histopathologic documentation of reflux-associated changes and evidence of tumor formation. Three cell lines were established from 2 of the reflux-associated tumors. We tested the ability of these cells to grow in vitro in tissue culture and in vivo as xenografts in an orthotopic location at the gastroesophageal junction. Furthermore, we performed a cytogenetic analysis and determined the array-based gene expression profiles of these 3 rodent carcinoma lines compared with normal esophageal mucosa. RESULTS: At 9 months, 12 of 12 rodents had histologic features of metaplastic columnar epithelium in the esophagus, with 7 having invasive carcinomas with glandular differentiation (either adenocarcinomas or adenosquamous carcinomas). The 3 cell lines established from 2 reflux-associated tumors were capable of sustained in vitro propagation and grew successfully as xenografts in both subcutaneous and orthotopic locations, confirming the tumorigenic nature of these lines. Despite their establishment from primary tumors with glandular features, the histology of the xenografts was that of well-differentiated squamous carcinomas. Karyotype analyses demonstrated cytogenetic heterogeneity and aneuploidy; furthermore, translocation (7:11) was present in all 3 lines. Array-based gene expression profiling confirmed upregulation of several cancer-related genes important in human esophageal cancer. Quantitative reverse transcription-polymerase chain reaction was used to confirm the differential expression of selected transcripts (vascular endothelial growth factor [VEGF], polo-like kinases [PLK], cyclin dependent kinase 4 [CDK4], hypoxia-inducible factor 1alpha [HIF1alpha], and insulin-like growth factor 1 [IGF-1]) in comparison with nonneoplastic esophageal mucosal scrapings. CONCLUSIONS: The rodent reflux model is capable of inducing metaplastic epithelial changes simulating Barrett esophagus, as well as subsequent neoplastic transformation, at a high frequency. Cell lines have been established from these tumors that are capable of in vitro and in vivo passaging. The rodent reflux model should be a valuable model for studying therapy and chemoprevention efforts for Barrett esophagus, whereas the established cell lines provide a useful resource for drug discovery and other high-throughput studies.

Multiple-laboratory comparison of microarray platforms.

Microarray technology is a powerful tool for measuring RNA expression for thousands of genes at once. Various studies have been published comparing competing platforms with mixed results: some find agreement, others do not. As the number of researchers starting to use microarrays and the number of cross-platform meta-analysis studies rapidly increases, appropriate platform assessments become more important. Here we present results from a comparison study that offers important improvements over those previously described in the literature. In particular, we noticed that none of the previously published papers consider differences between labs. For this study, a consortium of ten laboratories from the Washington, DC-Baltimore, USA, area was formed to compare data obtained from three widely used platforms using identical RNA samples. We used appropriate statistical analysis to demonstrate that there are relatively large differences in data obtained in labs using the same platform, but that the results from the best-performing labs agree rather well.