Statistical Designs for Two‐Color Spotted Microarray Experiments

Two-color cDNA or oligonucleotide-based spotted microarrays have been commonly used in measuring the expression levels of thousands of genes simultaneously. To realize the immense potential of this powerful new technology, budgeted within limited resources or other constraints, practical designs with high efficiencies are in demand. In this study, we address the design issue concerning the arrangement of the mRNA samples labeled with fluorescent dyes and hybridized on the slides. A normalization model is proposed to characterize major sources of systematic variation in a two-color microarray experiment. This normalization model establishes a connection between designs for two-color microarray experiments with a particular class of classical row-column designs. A heuristic algorithm for constructing A-optimal or highly efficient designs is provided. Statistical optimality results are found for some of the designs generated from the algorithm. It is believed that the constructed designs are the best or very close to the best possible for estimating the relative gene expression levels among the mRNA samples of interest.

[1]  G F V Glonek,et al.  Factorial and time course designs for cDNA microarray experiments. , 2004, Biostatistics.

[2]  D. Conniffe,et al.  Some incomplete block designs of maximum efficiency , 1975 .

[3]  S. Dudoit,et al.  Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. , 2002, Nucleic acids research.

[4]  M. Radmacher,et al.  Design of studies using DNA microarrays , 2002, Genetic epidemiology.

[5]  Bikas K. Sinha,et al.  24 Row-column designs , 1996, Design and analysis of experiments.

[6]  Tommi S. Jaakkola,et al.  Maximum-likelihood estimation of optimal scaling factors for expression array normalization , 2001, SPIE BiOS.

[7]  J. Kiefer.  ON THE NONRANDOMIZED OPTIMALITY AND RANDOMIZED NONOPTIMALITY OF SYMMETRICAL DESIGNS , 1958 .

[8]  Edgar Brunner,et al.  Efficient design and analysis of two colour factorial microarray experiments , 2006, Comput. Stat. Data Anal..

[9]  Ching-Shui Cheng,et al.  Optimality of Certain Asymmetrical Experimental Designs , 1978 .

[10]  O. Kempthorne.  The Efficiency Factor of an Incomplete Block Design , 1956 .

[11]  T. Speed,et al.  Design issues for cDNA microarray experiments , 2002, Nature Reviews Genetics.

[12]  M. Jacroux.  Some sufficient conditions for type 1 optimality with applications to regular graph designs , 1989 .

[13]  Sorin Drăghici,et al.  Data Analysis Tools for DNA Microarrays , 2003 .

[14]  G. Churchill,et al.  Experimental design for gene expression microarrays. , 2001, Biostatistics.

[15]  M. Jacroux,et al.  On the determination and construction of optimal row-column designs having unequal row and column sizes , 1991 .