Bayesian analysis of gene expression levels: statistical quantification of relative mRNA level across multiple strains or treatments

Genome Biol. 2002;3(12):RESEARCH0071. doi: 10.1186/gb-2002-3-12-research0071. Epub 2002 Nov 20.

Abstract

Background: Methods of microarray analysis that suit experimentalists using the technology are vital. Many methodologies discard the quantitative results inherent in cDNA microarray comparisons or cannot be flexibly applied to multifactorial experimental design. Here we present a flexible, quantitative Bayesian framework. This framework can be used to analyze normalized microarray data acquired by any replicated experimental design in which any number of treatments, genotypes, or developmental states are studied using a continuous chain of comparisons.

Results: We apply this method to Saccharomyces cerevisiae microarray datasets on the transcriptional response to ethanol shock, to SNF2 and SWI1 deletion in rich and minimal media, and to wild-type and zap1 expression in media with high, medium, and low levels of zinc. The method is highly robust to missing data, and yields estimates of the magnitude of expression differences and experimental error variances on a per-gene basis. It reveals genes of interest that are differentially expressed at below the twofold level, genes with high 'fold-change' that are not statistically significantly different, and genes differentially regulated in quantitatively unanticipated ways.

Conclusions: Anyone with replicated normalized cDNA microarray ratio datasets can use the freely available MacOS and Windows software, which yields increased biological insight by taking advantage of replication to discern important changes in expression level both above and below a twofold threshold. Not only does the method have utility at the moment, but also, within the Bayesian framework, there will be considerable opportunity for future development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bayes Theorem
  • DNA-Binding Proteins / genetics
  • Ethanol / pharmacology
  • Gene Deletion
  • Gene Expression Profiling / methods
  • Gene Expression Profiling / statistics & numerical data*
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / genetics*
  • Gene Expression Regulation, Fungal / physiology
  • Genotype
  • Models, Genetic
  • Nuclear Proteins*
  • Oligonucleotide Array Sequence Analysis / methods
  • Oligonucleotide Array Sequence Analysis / statistics & numerical data*
  • RNA, Fungal / metabolism*
  • RNA, Messenger / biosynthesis*
  • Saccharomyces cerevisiae Proteins / biosynthesis*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Species Specificity
  • Transcription Factors / genetics
  • Zinc

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ethanol
  • Zinc