A community-driven global reconstruction of human metabolism.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageMultiple 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/.Rannis research grant 100406022 Biotechnology and Biological Sciences Research Council (BBSRC) Engineering and Physical Sciences Research Council BB/C008219/1 European Union 201142 Knut and Alice Wallenberg Foundation BBSRC BB/F005938 BB/F00561X German Federal Ministry for Education and Research within the Virtual Liver Network 0315756 0315741 US National Institutes of Health GM088244 National Science Foundation 0643548 Cystic Fibrosis Research Foundation 1060 National Cancer Institute Science and Technology Facilities Council US National Institute of General Medical Sciences R01GM070923 R01GM080219 BioRange programme of The Netherlands Bioinformatics Centre under a Besluit Subsidies Investeringen Kennisinfrastructuur grant through The Netherlands Genomics Initiative SP1.2.4info:eu-repo/grantAgreement/EC/FP7/232816info:eu-repo/grantAgreement/EC/FP7/24926