A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1

Martin I. Sigurdsson, Neema Jamshidi, Eirikur Steingrimsson, Ines Thiele*, Bernhard T. Palsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

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.

Original languageEnglish
Article number140
JournalBMC Systems Biology
Volume4
DOIs
Publication statusPublished - 19 Oct 2010

Bibliographical note

Funding Information:
This work was supported by ERC grant agreement No. 232816 - SYSTEM_Us between the European Research Council and Bernhard Ø. Palsson and a Marie Curie International Reintegration Grant within the 7th European Community Framework Programme.

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