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Nucleic Acids Research 2005 33(17):5565-5573; doi:10.1093/nar/gki844
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Published online 4 October 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org


Article

Sub-array normalization subject to differentiation

Chao Cheng1 and Lei M. Li1,2,*

1Computational Biology, University of Southern California Los Angeles, CA, USA 2Mathematics, University of Southern California Los Angeles, CA, USA

*To whom correspondence should be addressed. Tel: +1 213 740 2407; Fax: +1 213 740 2437; Email: lilei{at}usc.edu

Received July 2, 2005. Revised August 31, 2005. Accepted August 31, 2005.

From microarray measurement, we seek differentiation of mRNA expressions among different biological samples. However, each array has a ‘block effect’ due to uncontrolled variation. The statistical treatment of reducing the block effect is usually referred to as normalization. Our perspective is to find a transformation that matches the distributions of hybridization levels of those probes corresponding to undifferentiated genes between arrays. We address two important issues. First, array-specific spatial patterns exist due to uneven hybridization and measurement process. Second, in some cases a substantially large portion of genes are differentially expressed between a target and a reference array. For the purpose of normalization we need to identify a subset that exclude those probes corresponding to differentially expressed genes and abnormal probes due to experimental variation. Least trimmed squares (LTS) is a natural choice to achieve this goal. Substantial differentiation is protected in LTS by setting an appropriate trimming fraction. To take into account any spatial pattern of hybridization, we divide each array into sub-arrays and normalize probe intensities within each sub-array. We illustrate the problem and solution through an Affymetrix spike-in dataset with defined perturbation and a dataset of primate brain expression.


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H. Ge, M. Wei, P. Fabrizio, J. Hu, C. Cheng, V. D. Longo, and L. M. Li
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[Abstract] [Full Text] [PDF]



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