title: Evaluation of bias-variance trade-off for commonly used post-summarizing normalization procedures in large-scale gene expression studies.
abstract: Normalization procedures are widely used in high-throughput genomic data analyses to remove various technological noise and variations. They are known to have profound impact to the subsequent gene differential expression analysis. Although there has been some research in evaluating different normalization procedures, few attempts have been made to systematically evaluate the gene detection performances of normalization procedures from the bias-variance trade-off point of view, especially with strong gene differentiation effects and large sample size. In this paper, we conduct a thorough study to evaluate the effects of normalization procedures combined with several commonly used statistical tests and MTPs under different configurations of effect size and sample size. We conduct theoretical evaluation based on a random effect model, as well as simulation and biological data analyses to verify the results. Based on our findings, we provide some practical guidance for selecting a suitable normalization procedure under different scenarios.
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, United States of America.
authors.forename: Xing
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.affiliation: Math Department, DePauw University, Greencastle, Indiana, United States of America.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000465:Algorithms; D015982:Bias; D003627:Data Interpretation, Statistical; D020869:Gene Expression Profiling / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D018401:Sample Size; D059467:Transcriptome