Abstract

Gene set analysis methods aim to determine whether an a priori defined set of genes shows statistically significant difference in expression on either categorical or continuous outcomes. Although many methods for gene set analysis have been proposed, a systematic analysis tool for identification of different types of gene set significance modules has not been developed previously. This work presents an R package, called MAVTgsa, which includes three different methods for integrated gene set enrichment analysis. (1) The one-sided OLS (ordinary least squares) test detects coordinated changes of genes in gene set in one direction, either up- or downregulation. (2) The two-sided MANOVA (multivariate analysis variance) detects changes both up- and downregulation for studying two or more experimental conditions. (3) A random forests-based procedure is to identify gene sets that can accurately predict samples from different experimental conditions or are associated with the continuous phenotypes. MAVTgsa computes the P values and FDR (false discovery rate) q-value for all gene sets in the study. Furthermore, MAVTgsa provides several visualization outputs to support and interpret the enrichment results. This package is available online.

Highlights

  • DNA microarray technology enables simultaneous monitoring of the expression level of a large number of genes for a given experimental study

  • Mootha et al [4] proposed gene set enrichment analysis (GSEA), which considers the entire distribution of a predefined gene set rather than a subset from the differential expression list

  • The MAVTgsa was applied to a P53 dataset

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Summary

Introduction

DNA microarray technology enables simultaneous monitoring of the expression level of a large number of genes for a given experimental study. Much initial research on methods for data analysis has focused on the techniques to identify a list of differentially expressed genes. After selection of a list of differentially expressed gene, the list is examined with biologically predefined gene sets to determine whether any sets are overrepresented in the list compared with the whole list ([1,2,3]). Mootha et al [4] proposed gene set enrichment analysis (GSEA), which considers the entire distribution of a predefined gene set rather than a subset from the differential expression list. Microarray experiments inherit various sources of biological and technical variability, and analysis of a gene set is expected to be more reproducible than an individual gene analysis

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