On November 13, 2011 at noon in room 377, Yuval will present a paper
discussing the separation and analysis of intrinsic and extrinsic
fluctuations in protein content of a cell using a dual-reporter
method:
http://www.pnas.org/content/early/2011/06/30/1018832108.full.pdf+html
Separating intrinsic from extrinsic fluctuations in dynamic biological
systems
Andreas Hilfinger and Johan Paulsson
From molecules in cells to organisms in ecosystems, biological
populations fluctuate due to the intrinsic randomness of individual
events and the extrinsic influence of changing environments. The
combined effect is often too complex for effective analysis, and
many studies therefore make simplifying assumptions, for example
ignoring either intrinsic or extrinsic effects to reduce the number
of model assumptions. Here we mathematically demonstrate how two
identical and independent reporters embedded in a shared
fluctuating environment can be used to identify intrinsic and
extrinsic noise terms, but also how these contributions are
qualitatively and quantitatively different from what has been
previously reported. Furthermore, we show for which classes of
biological systems the noise contributions identified by dual-reporter
methods correspond to the noise contributions predicted by correct
stochastic models of either intrinsic or extrinsic mechanisms. We find
that for broad classes of systems, the extrinsic noise from the dual-
reporter method can be rigorously analyzed using models that ignore
intrinsic stochasticity. In contrast, the intrinsic noise can be
rigorously analyzed using models that ignore extrinsic stochasticity
only under very special conditions that rarely hold in biology.
Testing whether the conditions are met is rarely possible and the dual-
reporter method may thus produce flawed conclusions about the
properties of the system, particularly about the intrinsic noise. Our
results contribute toward establishing a rigorous framework to analyze
dynamically fluctuating biological systems.