title: The effects of normalization on the correlation structure of microarray data.
abstract: BACKGROUND
  Stochastic dependence between gene expression levels in microarray data is of critical importance for the methods of statistical inference that resort to pooling test-statistics across genes. It is frequently assumed that dependence between genes (or tests) is sufficiently weak to justify the proposed methods of testing for differentially expressed genes. A potential impact of between-gene correlations on the performance of such methods has yet to be explored.
  
  
  RESULTS
  The paper presents a systematic study of correlation between the t-statistics associated with different genes. We report the effects of four different normalization methods using a large set of microarray data on childhood leukemia in addition to several sets of simulated data. Our findings help decipher the correlation structure of microarray data before and after the application of normalization procedures.
  
  
  CONCLUSIONS
  A long-range correlation in microarray data manifests itself in thousands of genes that are heavily correlated with a given gene in terms of the associated t-statistics. By using normalization methods it is possible to significantly reduce correlation between the t-statistics computed for different genes. Normalization procedures affect both the true correlation, stemming from gene interactions, and the spurious correlation induced by random noise. When analyzing real world biological data sets, normalization procedures are unable to completely remove correlation between the test statistics. The long-range correlation structure also persists in normalized data.
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, New York 14642, USA. Xing_Qiu@urmc.rochester.edu
authors.forename: Xing
authors.initials: X
authors.lastname: Qiu
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.forename: Lev
authors.initials: L
authors.lastname: Klebanov
authors.forename: Ndrei
authors.initials: N
authors.lastname: Yakovlev
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012984:Software; D018709:Statistics, Nonparametric; D013269:Stochastic Processes