Advanced significance analysis of microarray data based on weighted resampling: a comparative study and application to gene deletions in Mycobacterium bovis

Bioinformatics. 2004 Feb 12;20(3):357-63. doi: 10.1093/bioinformatics/btg417.

Abstract

Motivation: When analyzing microarray data, non-biological variation introduces uncertainty in the analysis and interpretation. In this paper we focus on the validation of significant differences in gene expression levels, or normalized channel intensity levels with respect to different experimental conditions and with replicated measurements. A myriad of methods have been proposed to study differences in gene expression levels and to assign significance values as a measure of confidence. In this paper we compare several methods, including SAM, regularized t-test, mixture modeling, Wilk's lambda score and variance stabilization. From this comparison we developed a weighted resampling approach and applied it to gene deletions in Mycobacterium bovis.

Results: We discuss the assumptions, model structure, computational complexity and applicability to microarray data. The results of our study justified the theoretical basis of the weighted resampling approach, which clearly outperforms the others.

Publication types

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

MeSH terms

  • Algorithms*
  • Data Interpretation, Statistical
  • Gene Deletion*
  • Gene Expression Profiling / methods*
  • Genetic Variation
  • Genome, Bacterial
  • Models, Genetic
  • Models, Statistical
  • Mycobacterium bovis / genetics*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Reproducibility of Results
  • Sample Size
  • Sensitivity and Specificity