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Timing of gene expression responses to environmental changes
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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.
Download a local version of the paper here
Gal Chechik
Daphne Koller