Abstract

Cells respond to environmental perturbations with changes in their gene expression that are coordinated in magnitude and time. Timing information about individual genes, rather than clusters, provides a refined way to view and analyze responses, but it is hard to estimate accurately. To analyze response timing of individual genes, we developed a parametric model that captures the typical temporal responses: an abrupt early response followed by a second transition to a steady state. This impulse model explicitly represents natural temporal properties such as the onset and the offset time, and can be estimated robustly, as demonstrated by its superior ability to impute missing values in gene expression data. Using response time of individual genes, we identify relations between gene function and their response timing, showing, for example, how cytosolic ribosomal genes are only repressed after the mitochondrial ribosome is activated. We further demonstrate a strong relation between the binding affinity of a transcription factor and the activation timing of its targets, suggesting that graded binding affinities could be a widely used mechanism for controlling expression timing. See online Supplementary Material at (www.liebertonline.com).