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Bioinformatics Advance Access published online on September 8, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti661
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 3, 2005
Revised August 25, 2005
Accepted September 1, 2005

Article

A two-stage normalization method for partially degraded mRNA microarray data

Li-yu D. Liu 1, Naisyin Wang 2*, Joanne R. Lupton 3, Nancy D. Turner 3, Robert S. Chapkin 3, and Laurie A. Davidson 3

1 Department of Statistics, Texas A&M University, College Station, Texas
2 Department of Statistics, Texas A&M University, College Station, Texas; Center for Environmental and Rural Health, Texas A&M University, College Station, Texas
3 Department of Nutrition and Food Science, Texas A&M University, College Station, Texas; Center for Environmental and Rural Health, Texas A&M University, College Station, Texas

* To whom correspondence should be addressed.
Naisyin Wang, E-mail: nwang{at}stat.tamu.edu


  Abstract

Motivation: The goal of the study is to obtain genetic information from exfoliated colonocytes in the fecal stream rather than directly from mucosa cells within the colon. The latter is obtained through invasive procedures. The difficulties encountered by this procedure are that certain probe information may be compromised due to partially degraded mRNA. Proper normalization is essential to obtaining useful information from these fecal array data.

Results: We propose a new two stage semiparametric normalization method motivated by the features observed in fecal microarray data. A location-scale transformation and a robust inclusion step were used to roughly align arrays within the same treatment. A nonparametric estimated non-linear transformation was then used to remove the potential intensity-based biases. We compared the performance of the new method in analyzing a fecal microarray dataset to those achieved by two existing normalization approaches: global median transformation and quantile normalization. The new method favorably compared to the global median and quantile normalization methods.

Availability: The R codes implementing the two-stage method may be obtained from the corresponding author.

Supplementary Information: Additional figures including scatter plots, MA plots and density plots of array differences may be found at http://stat.tamu.edu/~daisy/NSBRI/.


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