Multi-level mixed effects models for bead arrays.

Abstract

Bead arrays are becoming a popular platform for high-throughput expression arrays. However, the number of the beads targeting a transcript and the variation of their intensities differ from sample to sample in these arrays. This property results in different accuracy of expression intensities of a transcript across arrays. We provide evidence, with publicly available spike-in data, that the false discovery rate of differential expression is reduced by modeling bead-level variability with a multi-level mixed effects model. We compare the performance of our proposed model to existing analysis methods for bead arrays: the unweighted t-test and other weighted methods. Additionally, we provide theoretical insights into when the multi-level mixed effects model outperforms other methods. Finally, we provide a software program for differential expression analysis using the multi-level mixed effects model that analyzes tens of thousands of genes efficiently. The software program is freely available on web at http://ephpublic.aecom.yu.edu/sites/rkim/Supplementary.