Dataset Information

Quek2008 - Genome-scale metabolic network of Mus musculus

ABSTRACT: Quek2008 - Genome-scale metabolic network of Mus musculus This model is described in the article: On the reconstruction of the Mus musculus genome-scale metabolic network model. Quek LE, Nielsen LK. Genome Inform 2008; 21: 89-100 Abstract: Genome-scale metabolic modeling is a systems-based approach that attempts to capture the metabolic complexity of the whole cell, for the purpose of gaining insight into metabolic function and regulation. This is achieved by organizing the metabolic components and their corresponding interactions into a single context. The reconstruction process is a challenging and laborious task, especially during the stage of manual curation. For the mouse genome-scale metabolic model, however, we were able to rapidly reconstruct a compartmentalized model from well-curated metabolic databases online. The prototype model was comprehensive. Apart from minor compound naming and compartmentalization issues, only nine additional reactions without gene associations were added during model curation before the model was able to simulate growth in silico. Further curation led to a metabolic model that consists of 1399 genes mapped to 1757 reactions, with a total of 2037 reactions compartmentalized into the cytoplasm and mitochondria, capable of reproducing metabolic functions inferred from literatures. The reconstruction is made more tractable by developing a formal system to update the model against online databases. Effectively, we can focus our curation efforts into establishing better model annotations and gene-protein-reaction associations within the core metabolism, while relying on genome and proteome databases to build new annotations for peripheral pathways, which may bear less relevance to our modeling interest. This model is hosted on BioModels Database and identified by: MODEL1507180067. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.

SUBMITTER: Nicolas Le Novère

PROVIDER: MODEL1507180067 | BioModels | 2015-07-30

REPOSITORIES: BioModels

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			Action	DRS
	MODEL1507180067?filename=MODEL1507180067-biopax2.owl	Owl
	MODEL1507180067?filename=MODEL1507180067-biopax3.owl	Owl
	MODEL1507180067?filename=MODEL1507180067.m	Other
	MODEL1507180067?filename=MODEL1507180067.pdf	Pdf
	MODEL1507180067?filename=MODEL1507180067.png	Other

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Publications

On the reconstruction of the Mus musculus genome-scale metabolic network model.

Quek Lake-Ee LE Nielsen Lars K LK

Genome informatics. International Conference on Genome Informatics 20080101

Genome-scale metabolic modeling is a systems-based approach that attempts to capture the metabolic complexity of the whole cell, for the purpose of gaining insight into metabolic function and regulation. This is achieved by organizing the metabolic components and their corresponding interactions into a single context. The reconstruction process is a challenging and laborious task, especially during the stage of manual curation. For the mouse genome-scale metabolic model, however, we were able to ...[more]

PMID: 19425150

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Project description:Sigurdsson2010 - Genome-scale metabolic model of Mus Musculus (iMM1415) This model is described in the article: A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1. Sigurdsson MI, Jamshidi N, Steingrimsson E, Thiele I, Palsson BØ. BMC Syst Biol 2010; 4: 140 Abstract: BACKGROUND: Well-curated and validated network reconstructions are extremely valuable tools in systems biology. Detailed metabolic reconstructions of mammals have recently emerged, including human reconstructions. They raise the question if the various successful applications of microbial reconstructions can be replicated in complex organisms. RESULTS: We mapped the published, detailed reconstruction of human metabolism (Recon 1) to other mammals. By searching for genes homologous to Recon 1 genes within mammalian genomes, we were able to create draft metabolic reconstructions of five mammals, including the mouse. Each draft reconstruction was created in compartmentalized and non-compartmentalized version via two different approaches. Using gap-filling algorithms, we were able to produce all cellular components with three out of four versions of the mouse metabolic reconstruction. We finalized a functional model by iterative testing until it passed a predefined set of 260 validation tests. The reconstruction is the largest, most comprehensive mouse reconstruction to-date, accounting for 1,415 genes coding for 2,212 gene-associated reactions and 1,514 non-gene-associated reactions.We tested the mouse model for phenotype prediction capabilities. The majority of predicted essential genes were also essential in vivo. However, our non-tissue specific model was unable to predict gene essentiality for many of the metabolic genes shown to be essential in vivo. Our knockout simulation of the lipoprotein lipase gene correlated well with experimental results, suggesting that softer phenotypes can also be simulated. CONCLUSIONS: We have created a high-quality mouse genome-scale metabolic reconstruction, iMM1415 (Mus Musculus, 1415 genes). We demonstrate that the mouse model can be used to perform phenotype simulations, similar to models of microbe metabolism. Since the mouse is an important experimental organism, this model should become an essential tool for studying metabolic phenotypes in mice, including outcomes from drug screening. This model is hosted on BioModels Database and identified by: MODEL1507180055. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.