Abstract
BackgroundHandling the vast amount of gene expression data generated by genome-wide transcriptional profiling techniques is a challenging task, demanding an informed combination of pre-processing, filtering and analysis methods if meaningful biological conclusions are to be drawn. For example, a range of traditional statistical and computational pathway analysis approaches have been used to identify over-represented processes in microarray data derived from various disease states. However, most of these approaches tend not to exploit the full spectrum of gene expression data, or the various relationships and dependencies. Previously, we described a pathway enrichment analysis tool created in MATLAB that yields a Pathway Regulation Score (PRS) by considering signalling pathway topology, and the overrepresentation and magnitude of differentially-expressed genes (J Comput Biol 19:563–573, 2012). Herein, we extended this approach to include metabolic pathways, and described the use of a graphical user interface (GUI).ResultsUsing input from a variety of microarray platforms and species, users are able to calculate PRS scores, along with a corresponding z-score for comparison. Further pathway significance assessment may be performed to increase confidence in the pathways obtained, and users can view Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway diagrams marked-up to highlight impacted genes.ConclusionsThe PRS tool provides a filter in the isolation of biologically-relevant insights from complex transcriptomic data.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0358-2) contains supplementary material, which is available to authorized users.
Highlights
Handling the vast amount of gene expression data generated by genome-wide transcriptional profiling techniques is a challenging task, demanding an informed combination of pre-processing, filtering and analysis methods if meaningful biological conclusions are to be drawn
We and others previously attempted this by studying performance across a range of datasets derived from distinct conditions ([27] and references therein)
The data were originally created by Taneera et al [31], who compared gene expression levels in RNA isolated from human pancreatic islets taken from 9 type 2 diabetes (T2D) cadaver donors with RNA samples of pancreatic islets derived from 54 non-diabetic cadaver donors
Summary
Using input from a variety of microarray platforms and species, users are able to calculate PRS scores, along with a corresponding z-score for comparison. Further pathway significance assessment may be performed to increase confidence in the pathways obtained, and users can view Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway diagrams marked-up to highlight impacted genes
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