Comparison of rule- and ordinary differential equation-based dynamic model of DARPP-32 signalling network

PeerJ

article

Emilia M. Wysocka¹  Matthew Page²  James Snowden²  T. Ian Simpson¹ 

[1] School of Informatics, University of Edinburgh;UCB Celltech

关键词: Modeling molecular dynamics;    Rule-based modelling;    Ordinary differential equations;    DARPP-32;    Dopamine-dependent synaptic plasticity;    Kappa language;    Molecular signalling;    Molecular interactions;    Addiction;    Context and reward-related learning;   

DOI  :  10.7717/peerj.14516

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule- based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and dynamics, acquired through model simulations. In line with previous reports, we confirm that the Kappa model recapitulates the general dynamics of its ODE counterpart with minor differences. These occur when molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one. As reported for other molecular systems, we find that, also for the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, easing model reuse. In parallel with these analyses, we report a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of more complex dynamic models to study this important molecular system.

【 授权许可】

CC BY