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A community-driven global reconstruction of human metabolism

2013; Nature Portfolio; Volume: 31; Issue: 5 Linguagem: Inglês

10.1038/nbt.2488

1546-1696

Ines Thiele, Neil Swainston, Ronan M. T. Fleming, Andreas Hoppe, Swagatika Sahoo, Maike K. Aurich, Hulda S. Haraldsdóttir, Monica L. Mo, Óttar Rolfsson, Miranda D. Stobbe, Stefan Gretar Thorleifsson, Rasmus Ågren, Christian Bölling, Sergio Bordel, Arvind K. Chavali, Paul D. Dobson, Warwick B. Dunn, Lukas Endler, David Hala, Michael Hucka, Duncan Hull, Daniel Jameson, Neema Jamshidi, Jón J. Jónsson, Nick Juty, Sarah Keating, Intawat Nookaew, Nicolas Le Novère, Naglis Malys, Alexander Mazein, Jason A. Papin, Nathan D. Price, E Selkov, Martin I. Sigurðsson, Evangelos Simeonidis, Nikolaus Sonnenschein, Kieran Smallbone, Anatoly Sorokin, Hans van Beek, Dieter Weichart, Igor Goryanin, Jens Nielsen, Hans V. Westerhoff, Douglas B. Kell, Pedro Mendes, Bernhard Ø. Palsson,

Metabolomics and Mass Spectrometry Studies

The metabolic modeling community has curated information from five models to create the most comprehensive model of human metabolism to date. Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ∼2× more reactions and ∼1.7× more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type–specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/ .