Hierarchical Bayes models for cDNA microarray gene expression.

cDNA microarrays are used in many contexts to compare mRNA levels between samples of cells. Microarray experiments typically give us expression measurements on 1000-20 000 genes, but with few replicates for each gene. Traditional methods using means and standard deviations to detect differential expression are not satisfactory in this context. A handful of alternative statistics have been developed, including several empirical Bayes methods. In the present paper we present two full hierarchical Bayes models for detecting gene expression, of which one (D) describes our microarray data very well. We also compare the full Bayes and empirical Bayes approaches with respect to model assumptions, false discovery rates and computer running time. The proposed models are compared to existing empirical Bayes models in a simulation study and for a set of data (Yuen et al., 2002), where 27 genes have been categorized by quantitative real-time PCR. It turns out that the existing empirical Bayes methods have at least as good performance as the full Bayes ones.

[1]  Krishnarao Appasani,et al.  Experimental Design for Gene Expression Analysis , 2007, Bioarrays.

[2]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Gottardo,et al.  Statistical analysis of microarray data: a Bayesian approach. , 2003, Biostatistics.

[4]  A D Long,et al.  Improved Statistical Inference from DNA Microarray Data Using Analysis of Variance and A Bayesian Statistical Framework , 2001, The Journal of Biological Chemistry.

[5]  Gordon K Smyth,et al.  Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2004, Statistical applications in genetics and molecular biology.

[6]  Ingrid Lönnstedt Replicated microarray data , 2001 .

[7]  S. Dudoit,et al.  STATISTICAL METHODS FOR IDENTIFYING DIFFERENTIALLY EXPRESSED GENES IN REPLICATED cDNA MICROARRAY EXPERIMENTS , 2002 .

[8]  Sylvia Richardson,et al.  Bayesian Hierarchical Model for Identifying Changes in Gene Expression from Microarray Experiments , 2002, J. Comput. Biol..

[9]  Pierre Baldi,et al.  A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes , 2001, Bioinform..

[10]  Peter Green,et al.  Markov chain Monte Carlo in Practice , 1996 .

[11]  S. Dudoit,et al.  Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. , 2002, Nucleic acids research.

[12]  G. Parmigiani,et al.  A statistical framework for expression‐based molecular classification in cancer , 2002 .

[13]  Brunero Liseo,et al.  Elimination of nuisance parameters with reference priors , 1993 .

[14]  James O. Berger,et al.  A Catalog of Noninformative Priors , 1996 .

[15]  S. Sealfon,et al.  Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays. , 2002, Nucleic acids research.

[16]  Sylvia Richardson,et al.  Markov Chain Monte Carlo in Practice , 1997 .

[17]  G. Churchill,et al.  Experimental design for gene expression microarrays. , 2001, Biostatistics.

[18]  S. Dudoit,et al.  Microarray expression profiling identifies genes with altered expression in HDL-deficient mice. , 2000, Genome research.