The Interplay of Intrinsic and Extrinsic Bounded Noises in Biomolecular Networks

被引:30
作者
Caravagna, Giulio [1 ]
Mauri, Giancarlo [1 ]
d'Onofrio, Alberto [2 ]
机构
[1] Univ Milano Bicocca, Dipartimento Informat Sistemist & Comunicaz, Milan, Italy
[2] European Inst Oncol, Dept Expt Oncol, Milan, Italy
关键词
EXACT STOCHASTIC SIMULATION; GENE-EXPRESSION; PERIODIC PERTURBATION; PROTEIN EXPRESSION; POSITIVE-FEEDBACK; SWITCHES; FLUCTUATIONS; MULTISTABILITY; BISTABILITY; SUPPRESSION;
D O I
10.1371/journal.pone.0051174
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i) the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii) a model of enzymatic futile cycle and (iii) a genetic toggle switch. In (ii) and (iii) we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.
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页数:20
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