High-throughput genomics assays have revolutionized our understanding of the molecular etiology of human disease, molecular biology of cell lineage and genetic regulation of gene expression. Transcriptome profiling in particular has been widely applied to detect variation in transcript levels attributable to differences in disease state, cell type or regulatory genetics. As transcriptome profiling studies have expanded in size and scope, they have grown increasingly complex and consider multiple sources of biological and technical variation. Recent studies have simultaneously considered multiple dimensions of variation to understand the impact of cell type [1], tissue type [2], brain region [3], experimental stimuli [4], time duration following stimulus [5] or ancestry [1, 4, 6] on the genetic regulation of gene expression. More studies are including a disease axis, for example to characterize the role of regulatory genetics on late onset Alzheimer’s disease in multiple brain regions [7].
