DRPathway GUI

DRPAthway: DR analysis, with fast curve fitting procedures and the introduction of a pathway dose-response profile

NOTE: Currently works with following R versions: 2.15.1 to 2.15.2

Motivation: Gene expression data is widely used for evaluation of disease- or treatment-induced adverse biological effects. A common analysis step is aggregation of individual transcripts into pathways or gene sets. While both qualitative (e.g., which pathways are affected) and quantitative (e.g., fold-changes for individual genes) data analysis strategies are used, such approaches only partly meet the needs for human health risk assessment. Traditionally, quantitative risk assessment relies on apical endpoints (e.g., tumor incidence) collected from dose-response studies in humans or animal models. However, transcriptional profiling is now common in chemical safety testing, and is an important source of information for evaluation of health risks. To enable the quantitative pathway-based analysis of perturbations by potentially hazardous chemicals, it is necessary to integrate dose-response information. Unfortunately, existing methods are not well-suited to dose-response designs, where it is desirable to make a global summary of transcriptional response for each pathway while maintaining appropriate error control.

Solution: An interactive DR Pathway graphical user interface (GUI) application has been implemented for dose-response analysis of gene expression data at the pathway level, connected to annotation for the three Gene Ontology (GO) domains. Pathways enriched for dose-responsive genes are detected using a fast and valid testing procedure, controlled for multiple comparisons. Pathway-level dose-response profiles are generated with bootstrap-derived confidence intervals for quantitative assessment.

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