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Bioinformatics Advance Access originally published online on September 8, 2005
Bioinformatics 2005 21(21):4000-4006; 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{at}oxfordjournals.org

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

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

1Department of Agronomy, Biostatistic Division, National Taiwan University Taipei, Taiwan
2Department of Nutrition and Food Science, Texas A&M University College Station, TX, USA
3Center for Environmental and Rural Health, Texas A&M University College Station, TX, USA

*To whom correspondence should be addressed.

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 non-parametric 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 with those achieved by two existing normalization approaches: global median transformation and quantile normalization. The new method favorably compared with the global median and quantile normalization methods.

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

Contact: nwang{at}stat.tamu.edu

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/

Received on June 3, 2005; revised on August 25, 2005; accepted on September 1, 2005

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