Correlation Test to Assess Low-Level Processing of High-Density Oligonucleotide Microarray Data

BMC Bioinformatics. 2005 Mar 31;6:80. doi: 10.1186/1471-2105-6-80.

Abstract

Background: There are currently a number of competing techniques for low-level processing of oligonucleotide array data. The choice of technique has a profound effect on subsequent statistical analyses, but there is no method to assess whether a particular technique is appropriate for a specific data set, without reference to external data.

Results: We analyzed coregulation between genes in order to detect insufficient normalization between arrays, where coregulation is measured in terms of statistical correlation. In a large collection of genes, a random pair of genes should have on average zero correlation, hence allowing a correlation test. For all data sets that we evaluated, and the three most commonly used low-level processing procedures including MAS5, RMA and MBEI, the housekeeping-gene normalization failed the test. For a real clinical data set, RMA and MBEI showed significant correlation for absent genes. We also found that a second round of normalization on the probe set level improved normalization significantly throughout.

Conclusion: Previous evaluation of low-level processing in the literature has been limited to artificial spike-in and mixture data sets. In the absence of a known gold-standard, the correlation criterion allows us to assess the appropriateness of low-level processing of a specific data set and the success of normalization for subsets of genes.

MeSH terms

  • Algorithms
  • Cluster Analysis
  • Computational Biology
  • DNA Probes
  • Data Interpretation, Statistical
  • Databases, Genetic
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Genetic
  • Models, Statistical
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oligonucleotides / chemistry
  • RNA Probes
  • Research Design
  • Sensitivity and Specificity
  • Software

Substances

  • DNA Probes
  • Oligonucleotides
  • RNA Probes