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. 2013 Mar 19;9:649. doi: 10.1038/msb.2013.5

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Copyright © 2013, EMBO and Macmillan Publishers Limited

This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

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Illustration of the reconstruction process for iAdipocytes1809. (A) Human Metabolic Reaction (HMR) database was updated through the use of literature and previously published GEMs like HepatoNet1, Recon1 and EHMN and the Reactome database, with focus on the extensive lipid metabolism in adipocytes. HMR provides gene-transcript protein reaction (GTPR) links and GTPR represents functional relationships between genes/proteins and the corresponding reactions that they catalyze or control. Genes are first mapped to their transcripts, accounting for alternative splicing, the transcripts are mapped to the proteins and the proteins are then mapped to reactions based on the current knowledge of their effects on the reactions. In HMR, 75% of the reactions have GTPR and this allow us to incorporate proteome and transcriptome evidence in the adipocyte-specific network. The resulting gaps in the adipocyte-specific network were identified using the RAVEN Toolbox and filled manually using publicly available resources like KEGG, HumanCyc and Human Metabolic Atlas. Based on this, the comprehensive functional genome-scale metabolic model (GEM) for adipocytes, iAdipocytes1809, was reconstructed. (B) The Venn diagram illustrating the comparison of genes associated with reactions in the HMR and previously published literature-based models such as Recon 1, EHMN and HepatoNet 1. HMR includes all of the genes and associated reactions in previous published models. (C) Protein encoding genes and associated reactions with those genes included in iAdipocytes1809 based on proteome (1235 genes) and transcriptome (137 genes) data and evidence from previously published small-scale adipocytes model, iAB586 (244 genes). Another 193 genes and their associated reactions were included in the model due to connectivity constraints and known function of adipocytes. (D) iAdipocytes1809 is compared with iAB586 and fully connected generic human network, iHuman1512. iAdipocytes1809 contains all of the genes and associated reaction in iAB586 and all of the adipocyte-specific genes and associated reactions in iHuman1512.