Variance-modeled posterior inference of microarray data: detecting gene-expression changes in 3T3-L1 adipocytes

Bioinformatics
Albert HsiaoShankar Subramaniam

Abstract

Microarrays are becoming an increasingly common tool for observing changes in gene expression over a large cross section of the genome. This experimental tool is particularly valuable for understanding the genome-wide changes in gene transcription in response to thiazolidinedione (TZD) treatment. The TZD class of drugs is known to improve insulin-sensitivity in diabetic patients, and is clinically used in treatment regimens. In cells, TZDs bind to and activate the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPAR-gamma). Large-scale array analyses will provide some insight into the mechanisms of TZD-mediated insulin sensitization. Unfortunately, a theoretical basis for analyzing array data has not kept pace with the rapid adoption of this tool. The methods that are commonly used, particularly the fold-change approach and the standard t-test, either lack statistical rigor or resort to generalized statistical models that do not accurately estimate variability at low replicate numbers. We introduce a statistical framework that models the dependence of measurement variance on the level of gene expression in the context of a Bayesian hierarchical model. We compare several methods of parameter estimat...Continue Reading

Citations

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Aug 15, 2009·Systems and Synthetic Biology·Albert Hsiao, Shankar Subramaniam
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Feb 22, 2012·Nature Immunology·Shankar Subramaniam, Gene Hsiao
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