Bioinformatics Advance Access originally published online on July 1, 2004
Bioinformatics 2004 20(17):3196-3205; doi:10.1093/bioinformatics/bth384
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Bioinformatics vol. 20 issue 17 © Oxford University Press 2004; all rights reserved.
Normalization of microarray data using a spatial mixed model analysis which includes splines
1 AgResearch, Lincoln, New Zealand, 2 AgResearch, Invermay Research Centre, Mosgiel, New Zealand, and 3 AgResearch Molecular Biology Unit, Department of Biochemistry, University of Otago, Dunedin, New Zealand
Received on March 1, 2004; revised on April 22, 2004; accepted on June 22, 2004
Advance Access Publication July 1, 2004
Motivation: Microarray experiments with thousands of genes on a slide and multiple slides used in any experimental set represent a large body of data with many sources of variation. The identification of such sources of variation within microarray experimental sets is critical for correct deciphering of desired gene expression differences.
Results: We describe new methods for the normalization using spatial mixed models which include splines and analysis of two-colour spotted microarrays for within slide variation and for a series of slides. The model typically explains 45–85% of the variation on a slide with only 
1% of the total degrees of freedom. The results from our methods compare favourably with those from intensity dependent normalization loess methods where we accounted for twice as much uncontrolled and unwanted variation on the slides. We have also developed an index for each EST that combines the various measures of the differential response into a single value that researchers can use to rapidly assess the genes of interest.
Availability: GenStat code is available from the first author.
Contact: david.baird{at}agresearch.co.nz
* To whom correspondence should be addressed.
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