title: Incorporation of subject-level covariates in quantile normalization of miRNA data.
abstract: BACKGROUND
  Most currently-used normalization methods for miRNA array data are based on methods developed for mRNA arrays despite fundamental differences between the data characteristics. The application of conventional quantile normalization can mask important expression differences by ignoring demographic and environmental factors. We present a generalization of the conventional quantile normalization method, making use of available subject-level covariates in a colorectal cancer study.
  
  
  RESULTS
  In simulation, our weighted quantile normalization method is shown to increase statistical power by as much as 10 % when relevant subject-level covariates are available. In application to the colorectal cancer study, this increase in power is also observed, and previously-reported dysregulated miRNAs are rediscovered.
  
  
  CONCLUSIONS
  When any subject-level covariates are available, the weighted quantile normalization method should be used over the conventional quantile normalization method.
authors.affiliation: Department of Mathematics and Statistics, Utah State University, 3900 Old Main Hill, Logan, 84322-3900, UT, U.S.A. asu@biostatsolutions.com.|BioStat Solutions, Inc., 5280 Corporate Drive, Suite C200, Frederick, 21703, MD, U.S.A. asu@biostatsolutions.com.
authors.forename: Anvar
authors.initials: A
authors.lastname: Suyundikov
authors.affiliation: Department of Mathematics and Statistics, Utah State University, 3900 Old Main Hill, Logan, 84322-3900, UT, U.S.A. john.r.stevens@usu.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Stevens
authors.affiliation: Department of Mathematics and Statistics, Utah State University, 3900 Old Main Hill, Logan, 84322-3900, UT, U.S.A. chris.corcoran@usu.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Corcoran
authors.affiliation: Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 383 Colorow Road, Salt Lake City, 84108, UT, U.S.A. jennifer.herrick@hsc.utah.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrick
authors.affiliation: Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 383 Colorow Road, Salt Lake City, 84108, UT, U.S.A. roger.wolff@hsc.utah.edu.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 383 Colorow Road, Salt Lake City, 84108, UT, U.S.A. marty.slattery@hsc.utah.edu.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
mesh_terms: D000368:Aged; D000465:Algorithms; D015179:Colorectal Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical
chemical_list: D035683:MicroRNAs