Joint analysis of multiple cDNA microarray studies via multivariate mixed models applied to genetic improvement of...

In functional genomic laboratories, it is common to use the same microarray slide across studies, each investigating a unique biological question, and each analyzed separately due to computational limitations and/or because there is no hybridization of samples from different studies on one slide. However, the question of analyzing data from multiple studies is a major current issue in microarray data analysis because there are gains to be made in the accuracy of estimated effects by exploiting a covariance structure between gene expression data across studies. We propose an approach for combining multiple studies using multivariate mixed models, with the assumption of a nonzero correlation among genes across experiments, while imposing a null residual covariance. We applied this method to jointly analyze three experiments in genetics of cattle with a total of 54 arrays, each with 19,200 spots and 7,638 elements. The resulting seven-variate model contains 752,476 equations and 56 covariances. To identify differentially expressed genes, we applied model-based clustering to a linear combination of the random gene x variety interaction effect. We enhanced the biological interpretation of the results by applying an iterative algorithm to identify the gene ontology classes that significantly changed in each experiment. We found 118 elements with coordinate expression that clustered into distinct biological functions such as adipogenesis and protein turnover. These results contribute to our understanding of the mechanistic processes involved in adipogenesis and nutrient partitioning.