Statisticians can play a crucial role in the design of gene expression studies to ensure the most effective allocation of available resources. This paper considers Pareto optimal designs for gene expression studies involving 2-color microarrays. Pareto optimality enables the recommendation of designs that are particularly efficient for the effects of most interest to biologists. This is relevant in the microarray context where analysis is typically carried out separately for those effects. Our approach will allow for effects of interest that correspond to contrasts rather than solely considering parameters of the linear model. We further develop the approach to cater for additional experimental considerations such as contrasts that are of equal scientific interest. This amounts to partitioning all relevant contrasts into subsets of effects that are of equal importance. Based on the partitions, a penalty is employed in order to recommend designs for complex and varied microarray experiments. Finally, we address the issue of gene-specific dye bias. We illustrate using studies of leukemia and breast cancer.
Abstract. Experimental design is concerned with the problem of allocating resources within an experiment to ensure that objectives of the experiment are achieved at the minimum cost. This paper focuses on the generation of optimal or near-optimal designs for large and complex experiments where it is infeasible to carry out an exhaustive search of the design space. Optimal designs for gene expression studies, aimed at investigating the behaviour of genes, are considered, where the optimality criterion employed is Pareto optimality. We develop an adaptation of the metaheuristic method of Pareto simulated annealing to generate an approximation to the set of Pareto optimal designs for large and complex experiments. We develop algorithms that utilise response surface methodology to search systematically for the optimal values of parameters associated with Pareto simulated annealing and performance is evaluated using quality measures.
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