Peter C. Thomson Veterinary Biometry, Faculty of Veterinary Science University of Sydney Location: Carslaw 173 Time: 2pm Friday, August 12, 2011 Microarray analysis: a systematic approach using mixed-models and finite-mixtures Abstract: Microarrays measure the expression levels of many thousands of genes simultaneously, and these measurements are usually perfumed on different physiological states (e.g. tissue types, times, strains, etc.). A frequent goal is then to determine which genes are differentially expressed (DE) as opposed to those that are not differentially expressed (non-DE). Genes are classified as being DE if their expression levels differ "significantly" between two (or more) states, or show "unusual" behaviour in a particular state. A common approach is to consider one gene at a time (e.g. t-tests or ANOVA). However this poses a multiple testing problem which may in part be overcome by false discovery rate (FDR) control. An alternative approach is to develop a model for the evaluation of all the gene features simultaneously, and proceed as a model fitting rather than a hypothesis testing process. For this method, a two-stage analysis is performed. (1) All the normalised expression level data are analysed simultaneously using a large-scale linear mixed model. This model includes fixed effects to describe the physical design of the microarrays, as well as random effects to describe the overall effects of genes (G) and the effects of genes in different states (G.S). (2) A two-component mixture model (DE and non-DE) is then fitted to the BLUPs of the G.S effects. The mixture model is fitted using the E-M algorithm, and the process returns posterior probabilities of individual genes being DE. These posterior probabilities are used to classify which genes are DE, and an FDR-type strategy may be applied to these. However, further refinements to this process can be made by a simultaneous fitting of a mixture of linear mixed models. This method will be illustrated by the analysis of a large-scale microarray study of lactation in the tammar wallaby.