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

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 se...

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Bibliographic Details
Published in:Nucleic acids research 2012-09, Vol.40 (17), p.e133-e133
Main Authors: Wu, Di, Smyth, Gordon K
Format: Article
Language:English
Subjects:
Animals
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cameras
Data Interpretation, Statistical
Data processing
Female
Gene Expression Profiling - methods
Humans
Methods Online
Mice
Population genetics
Software
Statistics, Nonparametric
Tumors
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gks461