Investigating the two-moment characterisation of subcellular biochemical networks

JOURNAL OF THEORETICAL BIOLOGY

卷:260

Article

Ullah, Mukhtar¹  Wolkenhauer, Olaf^1,2 

[1] Univ Rostock, Dept Comp Sci, Syst Biol & Bioinformat Grp, D-18051 Rostock, Germany

[2] Stellenbosch Inst Adv Study STIAS, ZA-7600 Stellenbosch, South Africa

关键词: Noise;    Two-moment approximation;    Mean;    (Co)variance;    Cell cycle;   

DOI  :  10.1016/j.jtbi.2009.05.022

来源: Elsevier

【 摘 要 】

While ordinary differential equations (ODEs) form the conceptual framework for modelling many cellular processes, specific situations demand stochastic models to capture the influence of noise. The most common formulation of stochastic models for biochemical networks is the chemical master equation (CME). While stochastic simulations are a practical way to realise the CME, analytical approximations offer more insight into the influence of noise. Towards that end, the two-moment approximation (2MA) is a promising addition to the established analytical approaches including the chemical Langevin equation (CLE) and the related linear noise approximation (LNA). The 2MA approach directly tracks the mean and (co)variance which are coupled in general. This coupling is not obvious in CME and CLE and ignored by LNA and conventional ODE models. We extend previous derivations of 2MA by allowing (a) non-elementary reactions and (b) relative concentrations. Often, several elementary reactions are approximated by a single step. Furthermore, practical situations often require the use of relative concentrations. We investigate the applicability of the 2MA approach to the well established fission yeast cell cycle model. Our analytical model reproduces the clustering of cycle times observed in experiments. This is explained through multiple resettings of M-phase promoting factor (MPF), caused by the coupling between mean and (co)variance, near the G2/M transition. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free