OpWise: Operons aid the identification of differentially expressed genes in bacterial microarray experiments

BackgroundDifferentially expressed genes are typically identified by analyzing the variation between replicate measurements. These procedures implicitly assume that there are no systematic errors in the data even though several sources of systematic error are known.ResultsOpWise estimates the amount of systematic error in bacterial microarray data by assuming that genes in the same operon have matching expression patterns. OpWise then performs a Bayesian analysis of a linear model to estimate significance. In simulations, OpWise corrects for systematic error and is robust to deviations from its assumptions. In several bacterial data sets, significant amounts of systematic error are present, and replicate-based approaches overstate the confidence of the changers dramatically, while OpWise does not. Finally, OpWise can identify additional changers by assigning genes higher confidence if they are consistent with other genes in the same operon.ConclusionAlthough microarray data can contain large amounts of systematic error, operons provide an external standard and allow for reasonable estimates of significance. OpWise is available at http://microbesonline.org/OpWise.

[1]  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.

[2]  Trey Ideker,et al.  Testing for Differentially-Expressed Genes by Maximum-Likelihood Analysis of Microarray Data , 2000, J. Comput. Biol..

[3]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Russell D. Wolfinger,et al.  The contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster , 2001, Nature Genetics.

[5]  G. Church,et al.  Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation. , 2003, Genome research.

[6]  Dorothea K. Thompson,et al.  Global Transcriptome Analysis of the Heat Shock Response of Shewanella oneidensis , 2004, Journal of bacteriology.

[7]  Julio Collado-Vides,et al.  A powerful non-homology method for the prediction of operons in prokaryotes , 2002, ISMB.

[8]  Gary A. Churchill,et al.  Analysis of Variance for Gene Expression Microarray Data , 2000, J. Comput. Biol..

[9]  M. Gerstein,et al.  Relating whole-genome expression data with protein-protein interactions. , 2002, Genome research.

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

[11]  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..

[12]  K. Liang,et al.  Asymptotic Properties of Maximum Likelihood Estimators and Likelihood Ratio Tests under Nonstandard Conditions , 1987 .

[13]  S. Adhya,et al.  Suboperonic Regulatory Signals , 2003, Science's STKE.

[14]  Jean-Jacques Daudin,et al.  Determination of the differentially expressed genes in microarray experiments using local FDR , 2004, BMC Bioinformatics.

[15]  Arkady B. Khodursky,et al.  Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Markus J. Herrgård,et al.  Integrating high-throughput and computational data elucidates bacterial networks , 2004, Nature.

[17]  Yu Qiu,et al.  Predicting bacterial transcription units using sequence and expression data , 2003, ISMB.

[18]  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.

[19]  S. Salzberg,et al.  Prediction of operons in microbial genomes. , 2001, Nucleic acids research.

[20]  Katherine H. Huang,et al.  A novel method for accurate operon predictions in all sequenced prokaryotes , 2005, Nucleic acids research.

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

[22]  Chiara Sabatti,et al.  Co-expression pattern from DNA microarray experiments as a tool for operon prediction , 2002, Nucleic Acids Res..

[23]  Ingrid Lönnstedt Replicated microarray data , 2001 .

[24]  John D. Storey,et al.  Statistical significance for genomewide studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Thomas Blumenthal,et al.  Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. , 2003, Genome research.

[26]  Lucila Ohno-Machado,et al.  Analysis of matched mRNA measurements from two different microarray technologies , 2002, Bioinform..