### Concepts of intrinsic and extrinsic origins of stochastic fluctuations

11 December 2009

Andreas Hilfinger

Paulsson Lab

Department of Systems Biology

Harvard Medical School

#### Abstract

Many cellular processes exhibit significant fluctuations. That is because inherently probabilistic chemical reactions generate spontaneous fluctuations in low copy number components which are then passed on through large interaction networks, potentially affecting many other components. Quantitative analyses of biological dynamics are therefore increasingly focusing on stochastic effects, trying to understand where fluctuations originate and how they are transmitted through networks. However, because many details about the (often non-linear) interaction networks of interest are unknown, analyzing the stochastic dynamics of biological systems is virtually impossible without making very unreliable model assumptions.

A way out of this dilemma is to focus on subnetworks whose properties we can (presumably) model with confidence and treat the rest of the network as an unspecified fluctuating environment. Here, we analyze whether such an approach can be used to divide fluctuations into two categories: intrinsic fluctuations (due to the inherent stochasticity of the subnetwork) and extrinsic fluctuations (due to the randomness of the environment in which the subnetwork is embedded). Furthermore, we address the question whether intrinsic and extrinsic contributions to fluctuations within a subnetwork can be inferred experimentally using a dual reporter approach.

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