190 Feedback Control in Systems Biology
that hierarchical control might be important for achieving robustness. The
complex feedback structures encountered in vivo were shown to confer robust
precision and adjustability of the clock while avoiding catastrophic failure.
Two recent papers have proposed effective strategies for overcoming the
local, one-parameter-at-a-time limitations of traditional sensitiv ity analysis.
In [23], the authors used sensitivity analysis to validate a new computational
model of signal transducer and activator of transcription-3 (Stat3) pathway
kinetics, a signaling network involved in e mbryonic stem cell self-renewal.
Transient pathway behaviour was simulated for a 40-fold range of values for
each model parameter in order ...