Abstract

BackgroundAn important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases.ResultsHere we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina.ConclusionsGeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions, overlays of genes onto KEGG pathway diagrams and heatmaps of expression intensity values. GeneMesh is freely available online at http://proteogenomics.musc.edu/genemesh/.

Highlights

  • An important objective of DNA microarray-based gene expression experimentation is determining interrelationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases

  • Additional information stored in the database includes gene ontology information for each Gene ID, HomoloGene IDs and GeneMesh Database statistics

  • GeneIDs in each Medical Subject Headings (MeSH) category are linked to information at National Center for Biotechnology Information (NCBI) Entrez Gene and a hypergeometric probability value [11] for the MeSH category is provided

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Summary

Results

GeneMesh displays a table of all MeSH subcategories detected from the input DNA microarray data file (Figure 1). In addition to relating input genes to MeSH categories, the GeneMesh program performs a number of useful upfront operations on input expression data including viewing of all genes in the data set with links to Entrez Gene summaries (using the 'V' action link), viewing of expression intensity values of genes in the data set (using the 'VIV' action link), grouping of genes in relation to gene ontologies (including biological processes, molecular functions and cellular components using the 'B', 'M' and 'C' action links, respectively), mapping of GeneIDs of individual genes or clusters of genes to KEGG pathway diagrams (using the 'K' action link) and generating heatmaps of expression intensities (using the 'H' action link). The GeneMesh web site provides access to tutorials, which are offered in both html and video formats

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