A community-driven global reconstruction of human metabolism
Ines Thiele, Neil Swainston, Ronan M T Fleming, Andreas Hoppe, Swagatika Sahoo, Maike K Aurich, Hulda Haraldsdottir, Monica L Mo, Ottar Rolfsson, Miranda D Stobbe, Stefan G Thorleifsson, Rasmus Agren, Christian Blling, Sergio Bordel, Arvind K Chavali, Paul Dobson, Warwick B Dunn, Lukas Endler,David Hala, Michael Hucka, Duncan Hull, Daniel Jameson, Neema Jamshidi, Jon J Jonsson, Nick Juty, Sarah Keating, Intawat Nookaew, Nicolas Le Novère, Naglis Malys, Alexander Mazein, Jason A Papin, Nathan D Price, Evgeni Selkov Sr, Martin I Sigurdsson, Evangelos Simeonidis,Nikolaus Sonnenschein, Kieran Smallbone,Anatoly Sorokin,Johannes H G M van Beek, Dieter Weichart,Igor Goryanin,Jens Nielsen, Hans V Westerhoff,Douglas B Kell,Pedro Mendes & Bernhard Palsson.
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/.