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- Title
Multiplex meta-analysis of RNA expression to identify genes with variants associated with immune dysfunction.
- Authors
Morgan, Alexander A.; Pyrgos, Vasilios J.; Nadeau, Kari C.; Williamson, Peter R.; Butte, Atul Janardhan
- Abstract
Objective We demonstrate a genome-wide method for the integration of many studies of gene expression of phenotypically similar disease processes, a method of multiplex meta-analysis. We use immune dysfunction as an example disease process. Design We use a heterogeneous collection of datasets across human and mice samples from a range of tissues and different forms of immunodeficiency. We developed a method integrating Tibshirani's modified t-test (SAM) is used to interrogate differential expression within a study and Fisher's method for omnibus meta-analysis to identify differentially expressed genes across studies. The ability of this overall gene expression profile to prioritize disease associated genes is evaluated by comparing against the results of a recent genome wide association study for common variable immunodeficiency (CVID). Results Our approach is able to prioritize genes associated with immunodeficiency in general (area under the ROC curve = 0.713) and CVID in particular (area under the ROC curve = 0.643). Conclusions This approach may be used to investigate a larger range of failures of the immune system. Our method may be extended to other disease processes, using RNA levels to prioritize genes likely to contain disease associated DNA variants.
- Subjects
META-analysis; RNA; GENE expression; IMMUNODEFICIENCY; T-test (Statistics)
- Publication
Journal of the American Medical Informatics Association, 2012, Vol 19, Issue 2, p284
- ISSN
1067-5027
- Publication type
Article
- DOI
10.1136/amiajnl-2011-000657