Dataset Information

Smallbone2010_Genome_Scale_Yeast_Kinetics

ABSTRACT: This is the model described in the article: Towards a genome-scale kinetic model of cellular metabolism Smallbone K, Simeonidis E, Swainston N, Mendes P. BMC Syst Biol. 2010 Jan 28;4(1):6. PMID: 20109182 , doi: 10.1186/1752-0509-4-6 Abstract: CKGROUND: Advances in bioinformatic techniques and analyses have led to the availability of genome-scale metabolic reconstructions. The size and complexity of such networks often means that their potential behaviour can only be analysed with constraint-based methods. Whilst requiring minimal experimental data, such methods are unable to give insight into cellular substrate concentrations. Instead, the long-term goal of systems biology is to use kinetic modelling to characterize fully the mechanics of each enzymatic reaction, and to combine such knowledge to predict system behaviour. RESULTS: We describe a method for building a parameterized genome-scale kinetic model of a metabolic network. Simplified linlog kinetics are used and the parameters are extracted from a kinetic model repository. We demonstrate our methodology by applying it to yeast metabolism. The resultant model has 956 metabolic reactions involving 820 metabolites, and, whilst approximative, has considerably broader remit than any existing models of its type. Control analysis is used to identify key steps within the system. CONCLUSIONS: Our modelling framework may be considered a stepping-stone toward the long-term goal of a fully-parameterized model of yeast metabolism. The model (see additional file 1) is available in SBML format from the BioModels database (BioModels ID: MODEL1001200000) and at http://www.mcisb.org/resources/genomescale/ . This SBML representation of the yeast metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org). This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

OTHER RELATED OMICS DATASETS IN: PXD016589PRJNA84673PRJNA89881PRJNA89887PRJNA89909PRJNA89879

SUBMITTER: Kieran Smallbone

PROVIDER: MODEL1001200000 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Publications

Towards a genome-scale kinetic model of cellular metabolism.

Smallbone Kieran K Simeonidis Evangelos E Swainston Neil N Mendes Pedro P

BMC systems biology 20100128

<h4>Background</h4>Advances in bioinformatic techniques and analyses have led to the availability of genome-scale metabolic reconstructions. The size and complexity of such networks often means that their potential behaviour can only be analysed with constraint-based methods. Whilst requiring minimal experimental data, such methods are unable to give insight into cellular substrate concentrations. Instead, the long-term goal of systems biology is to use kinetic modelling to characterize fully th ...[more]

PMID: 20109182

Publication: 1/249

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Project description:In order to elucidate transcriptional and metabolic networks associated with Lys metabolism, we utilized developing seeds as a system in which Lys synthesis could be stimulated developmentally without application of chemicals and coupled this to a T-DNA insertion knockout mutation impaired in Lys catabolism. This seed-specific metabolic perturbation stimulated Lys accumulation starting from the initiation of storage reserve accumulation. Our results revealed that the response of seed metabolism to the inducible alteration of Lys metabolism was relatively minor, however, that which was observable operated in a modular manner. They also demonstrated that Lys metabolism is strongly associated with the operation of the TCA cycle, whilst largely disconnected from other metabolic networks. In contrast, the inducible alteration of Lys metabolism was strongly associated with gene networks, stimulating the expression of hundreds of genes controlling anabolic processes that are associated with plant performance and vigor, whilst suppressing a small number of genes associated with plant stress interactions. The most pronounced effect of the developmentally-inducible alteration of Lys metabolism was an induction of expression of a large set of genes encoding ribosomal proteins as well as genes encoding translation initiation and elongation factors, all of which are associated with protein synthesis. With respect to metabolic regulation, the inducible alteration of Lys metabolism was primarily associated with altered expression of genes belonging to networks of amino acids and sugar metabolism. The combined data are discussed within the context of network interactions both between and within metabolic and transcriptional control systems. Experiment Overall Design: Arabidopsis thaliana (WS) seeds of the WT and KD genotype (Zhu and Galili, 2003)were germinated on soil and grown in the greenhouse (23oC). Flowers were marked and at given time intervals following flowering (14DAF to Dry ). Maturing siliques were collected, then seeds were dissected from siliques . Mature seeds were collected at the end of the desiccation period and stored at 4ºC. Two repeats were collected from each time point. Three to five thousands seeds were harvested for each extraction.

Dataset Information

Smallbone2010_Genome_Scale_Yeast_Kinetics

Publications

Towards a genome-scale kinetic model of cellular metabolism.

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