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Published May 2013 | Accepted Version + Supplemental Material
Journal Article Open

A community-driven global reconstruction of human metabolism

Abstract

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/.

Additional Information

© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. Received 7 September 2012; accepted 19 December 2012; published online 3 March 2013. I.T. was supported, in part, by a Marie Curie International Reintegration Grant (249261) within the 7th European Community Framework Program. I.T., O.R., S.G.T. and M.A. were supported by the European Research Council grant proposal number 232816. S.S. and H.H. were supported by a Rannis research grant (100406022). Authors from Manchester thank the Biotechnology and Biological Sciences Research Council (BBSRC), and Engineering and Physical Sciences Research Council for their funding of the Manchester Centre for Integrative Systems Biology (grant BB/C008219/1), H.W. for Bioprocessing Research Industry Club grants, and P.M. and N. Swainston for support from the European Union FP7 project UNICELLSYS (grant agreement 201142). The Knut and Alice Wallenberg Foundation supported R.A., S.B. and I.N.; D.J. thanks the BBSRC for funding of Systems Approaches to Biological Research grants BB/F005938 and BB/F00561X. A.H. and C.B. were supported by the German Federal Ministry for Education and Research within the Virtual Liver Network (grant numbers 0315756 and 0315741). A.K.C. and J.A.P. acknowledge funding from the US National Institutes of Health (grant GM088244), National Science Foundation (grant 0643548) and Cystic Fibrosis Research Foundation (grant 1060). N.D.P. was supported by a National Cancer Institute to Independence Award in Cancer Research. I.G. thanks the Science and Technology Facilities Council for Scottish Bioinformatics Research Network funding. M.H. and P.M. thank the US National Institute of General Medical Sciences for support under grants R01GM070923 and R01GM080219. M.D.S. thanks the BioRange programme (project SP1.2.4) of The Netherlands Bioinformatics Centre for support under a Besluit Subsidies Investeringen Kennisinfrastructuur grant through The Netherlands Genomics Initiative. Author Contributions: I.T. and N. Swainston led the project and developed the reconstruction. I.T., N. Swainston, B.Ø.P., P.M. and D.K. wrote the manuscript. B.Ø.P., D.B.K. and P.M. conceived the project. R.M.T.F. and A.H. performed validation of the reconstruction. S.S. and M.L.M. performed substantial manual curation of the reconstruction. M.K.A., H.H., O.R., M.D.S. and S.G.T. contributed to the analysis of the reconstruction and its models. I.T., N. Swainston, R.M.T.F., A.H., S.S., M.K.A., H.H., M.L.M., O.R., M.D.S., S.G.T., R.A., C.B., S.B., A.K.C., P.D., W.B.D., L.E., D. Hala, M.H., D. Hull, D.J., N. Jamshidi, J.J.J., N. Juty, S.K., I.N., N.L.N., N.M., A.M., J.A.P., N.D.P., E. Selkov, M.I., E. Simeonidis, N. Sonnenschein, K.S., A.S., J.H.G.M.v.B., D.W., I.G., J.N., H.V.W., D.B.K., P.M. and B.Ø.P. attended one or more jamboree meetings and provided manual curation of the reconstruction.

Attached Files

Accepted Version - nihms514169.pdf

Supplemental Material - nbt.2488-S1.pdf

Supplemental Material - nbt.2488-S2.zip

Supplemental Material - nbt.2488-S3.xls

Supplemental Material - nbt.2488-S4.xls

Supplemental Material - nbt.2488-S5.xls

Supplemental Material - nbt.2488-S6.xls

Supplemental Material - nbt.2488-S7.xls

Supplemental Material - nbt.2488-S8.xls

Supplemental Material - nbt.2488-S9.xls

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Additional details

Created:
August 19, 2023
Modified:
October 24, 2023