Camera: a competitive gene set test accounting for inter-gene correlation

Wu, D; Smyth, GK

Author(s): Wu, D; Smyth, GK;
Details: Publication Year 2012-09,Volume 40,Issue #17,Page -
Journal Title: NUCLEIC ACIDS RESEARCH
Publication Type: Journal Article
Abstract: Competitive gene set tests are commonly used in molecular pathway analysis to test for enrichment of a particular gene annotation category amongst the differential expression results from a microarray experiment. Existing gene set tests that rely on gene permutation are shown here to be extremely sensitive to inter-gene correlation. Several data sets are analyzed to show that inter-gene correlation is non-ignorable even for experiments on homogeneous cell populations using genetically identical model organisms. A new gene set test procedure (CAMERA) is proposed based on the idea of estimating the inter-gene correlation from the data, and using it to adjust the gene set test statistic. An efficient procedure is developed for estimating the inter-gene correlation and characterizing its precision. CAMERA is shown to control the type I error rate correctly regardless of inter-gene correlations, yet retains excellent power for detecting genuine differential expression. Analysis of breast cancer data shows that CAMERA recovers known relationships between tumor subtypes in very convincing terms. CAMERA can be used to analyze specified sets or as a pathway analysis tool using a database of molecular signatures.
Publisher: OXFORD UNIV PRESS
Keywords: ENRICHMENT ANALYSIS; MICROARRAY DATA; EXPRESSION DATA; FUNCTIONAL CATEGORIES; LINEAR-MODELS; PROGENITORS; POPULATION; ANNOTATION; PROFILES; PATHWAYS
Research Division(s): Bioinformatics
Publisher's Version: https://doi.org/10.1093/nar/gks461
Open Access at Publisher's Site: http://nar.oxfordjournals.org/content/40/17/e133.long
Terms of Use/Rights Notice: Copyright © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Creation Date: 2012-09-01 12:00:00

Last Modified: 2015-09-02 04:05:15