Abstract

Normalization is an important step in the analysis of microarray data of transcription profiles as systematic non-biological variations often arise from the multiple steps involved in any transcription profiling experiment. Existing methods for data normalization often assume that there are few or symmetric differential expression, but this assumption does not always hold. Alternatively, non-differentially expressed genes may be used for array normalization. However, it is unknown at the outset which genes are non-differentially expressed. In this paper we propose a hierarchical mixture model framework to simultaneously identify non-differentially expressed genes and normalize arrays using these genes. The Fisher's information matrix corresponding to array effects is derived, which provides useful intuition for guiding the choice of array normalization method. The operating characteristics of the proposed method are evaluated using simulated data. The simulations conducted under a wide range of parametric configurations suggest that the proposed method provides a useful alternative for array normalization. For example, the proposed method has better sensitivity than median normalization under modest prevalence of differentially expressed genes and when the magnitudes of over-expression and under-expression are not the same. Further, the proposed method has properties similar to median normalization when the prevalence of differentially expressed genes is very small. Empirical illustration of the proposed method is provided using a liposarcoma study from MSKCC to identify genes differentially expressed between normal fat tissue versus liposarcoma tissue samples.

Submitted: December 20, 2007 · Accepted: December 5, 2008 · Published: February 4, 2009

Recommended Citation

Qin, Li-Xuan and Satagopan, Jaya M. (2009) "Normalization Method for Transcriptional Studies of Heterogeneous Samples – Simultaneous Array Normalization and Identification of Equivalent Expression," Statistical Applications in Genetics and Molecular Biology: Vol. 8 : Iss. 1, Article 10.
DOI: 10.2202/1544-6115.1339
Available at: http://www.bepress.com/sagmb/vol8/iss1/art10

Related Files

affy.norm.supplementary.figures.pdf (595 kB)
Supplementary Figures
ease.159genes.identifiedByProposedMethod.htm (300 kB)
EASE results for 159 genes identified by the proposed method only
ease.273genes.identifiedByMedianNormalization.htm (322 kB)
EASE results for 273 genes identified by the median normalization only