细胞代谢与调控的数学模拟和分析

Mathematical simulation and analysis of cellular metabolism and regulation.

作者信息

Goryanin I, Hodgman T C, Selkov E

机构信息

Laboratory for Metabolic Modeling and Bioinformatics, The Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia, Advanced Technology and Informatics Unit, GlaxoWellcome Medicines Research Centre, Gunnels Wood Road, Stevenage,UK.

出版信息

Bioinformatics. 1999 Sep;15(9):749-58. doi: 10.1093/bioinformatics/15.9.749.

DOI:10.1093/bioinformatics/15.9.749

PMID:10498775

Abstract

MOTIVATION

A better understanding of the biological phenomena observed in cells requires the creation and analysis of mathematical models of cellular metabolism and physiology. The formulation and study of such models must also be simplified as far as possible to cope with the increasing complexity demanded and exponential accumulation of the metabolic reconstructions computed from sequenced genomes.

RESULTS

A mathematical simulation workbench, DBsolve, has been developed to simplify the derivation and analysis of mathematical models. It combines: (i) derivation of large-scale mathematical models from metabolic reconstructions and other data sources; (ii) solving and parameter continuation of non-linear algebraic equations (NAEs), including metabolic control analysis; (iii) solving the non-linear stiff systems of ordinary differential equations (ODEs); (iv) bifurcation analysis of ODEs; (v) parameter fitting to experimental data or functional criteria based on constrained optimization. The workbench has been successfully used for dynamic metabolic modeling of some typical biochemical networks (Dolgacheva et al., Biochemistry (Moscow), 6, 1063-1068, 1996; Goldstein and Goryanin, Mol. Biol. (Moscow), 30, 976-983, 1996), including microbial glycolytic pathways, signal transduction pathways and receptor-ligand interactions.

AVAILABILITY

DBsolve 5. 00 is freely available from http://websites.ntl.com/ approximately igor.goryanin.

CONTACT

gzz78923@ggr.co.uk

摘要

动机

要更好地理解在细胞中观察到的生物学现象，需要创建和分析细胞代谢与生理学的数学模型。此类模型的构建与研究还必须尽可能简化，以应对代谢重建（根据测序基因组计算得出）所需的日益增加的复杂性以及指数级积累。

结果

已开发出一个数学模拟工作台DBsolve，用于简化数学模型的推导与分析。它结合了：（i）从代谢重建和其他数据源推导大规模数学模型；（ii）求解非线性代数方程（NAE）并进行参数延拓，包括代谢控制分析；（iii）求解常微分方程（ODE）的非线性刚性系统；（iv）对ODE进行分岔分析；（v）基于约束优化对实验数据或功能标准进行参数拟合。该工作台已成功用于一些典型生化网络的动态代谢建模（多尔加乔娃等人，《生物化学（莫斯科）》，6，1063 - 1068，1996；戈尔茨坦和戈里亚宁，《分子生物学（莫斯科）》，30，976 - 983，1996），包括微生物糖酵解途径、信号转导途径和受体 - 配体相互作用。