Estimating cis and trans contributions to differences in gene regulation

We describe a coordinate system and associated hypothesis testing framework for determining whether cis or trans regulation is responsible for differences in gene expression between two homozygous strains or species. We apply our framework to data from single replicate studies on yeast strains and human-chimpanzee hybrid cells, as well as to data from a mouse study with replicates, showing marked differences between our gene regulatory assignments and those previously reported. We also show how our multi-sample framework can determine the context dependency of cis and trans effects as well as explicitly model different hypotheses regarding the underlying mechanism of trans regulation.