Cited by 1,019Microbial Metabolic Engineering and BioproductionBioinformatics and Genomic NetworksGene Regulatory Network Analysis

A community-driven global reconstruction of human metabolism

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Thiele, Ines, Swainston, Neil, Fleming, Ronan M T, Hoppe, Andreas, Sahoo, Swagatika, Aurich, Maike K, Haraldsdottir, Hulda, Mo, Monica L +38 more·2013·Nature Biotechnology

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/.

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Authors
Thiele, I., Swainston, N., Fleming, R. M. T., Hoppe, A., Sahoo, S., Aurich, M. K., Haraldsdottir, H., Mo, M. L., Rolfsson, O., Stobbe, M. D., Thorleifsson, S. G., Agren, R., Bölling, C., Bordel, S., Chavali, A. K., Dobson, P., Dunn, W. B., Endler, L., Hala, D., Hucka, M., Hull, D., Jameson, D., Jamshidi, N., Jonsson, J. J., Juty, N., Keating, S., Nookaew, I., Le Novère, N., Malys, N., Mazein, A., Papin, J. A., Price, N. D., Selkov, E., Sigurdsson, M. I., Simeonidis, E., Sonnenschein, N., Smallbone, K., Sorokin, A., van Beek, J. H. G. M., Weichart, D., Goryanin, I., Nielsen, J., Westerhoff, H. V., Kell, D. B., Mendes, P., & Palsson, B. Ø.
Affiliations
  • University of Iceland (IS)
  • University of Manchester (GB)
  • Charité – Universitätsmedizin Berlin (DE)
  • University of California San Diego (US)
  • Netherlands Bioinformatics Centre (NL)
  • Chalmers University of Technology (SE)
  • University of Virginia (US)
  • University of Sheffield (GB)
  • Manchester Academic Health Science Centre (GB)
  • University of Vienna (AT)
  • University of North Texas (US)
  • California Institute of Technology (US)
  • European Bioinformatics Institute (GB)
  • University of Edinburgh (GB)
  • Institute for Systems Biology (US)
  • University of Luxembourg (LU)
  • Constructor University (DE)
  • Russian Academy of Sciences (RU)
  • Okinawa Institute of Science and Technology Graduate University (JP)
Corresponding author
Thiele, Ines
Venue
Nature Biotechnology
Published
2013-03-03
Volume
31
Issue
5
Pages
419-425
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2132218677
Cited by
1,019
References
52
Citations by year
2026: 28 · 2025: 35 · 2024: 45 · 2023: 45 · 2022: 45 · 2021: 60 · 2020: 82 · 2019: 93 · 2018: 101 · 2017: 125 · 2016: 98 · 2015: 116 · 2014: 95 · 2013: 51
FWCI
53.59
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • MIMS EPrints (University of Southampton) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Chalmers Publication Library (Chalmers University of Technology) (acceptedVersion)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • UvA-DARE (University of Amsterdam) (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
  • Hirsla (Landspítali University Hospital) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • National Science Foundation (0643548, 0315756)
  • Bioprocessing Research Industry Club
  • European Commission (249261, 201142)
  • Knut och Alice Wallenbergs Stiftelse
  • National Institutes of Health
  • Directorate for Biological Sciences
  • Engineering and Physical Sciences Research Council (BBC0082191)
  • Biotechnology and Biological Sciences Research Council (BB/C008219/1, BB/E006248/1, BBS/E/B/000C0419, BB/C008219, BB/J019305/1, BB/F00561X, 201142, BB/F005938)
  • Science and Technology Facilities Council
  • National Cancer Institute
  • National Institute of General Medical Sciences (R01GM080219, R01GM070923, R01GM088244, GM088244, U01GM102098)
  • FP7 Ideas: European Research Council (232816)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
metabolic network topology, inborn errors of metabolism, metabolic biomarkers, metabolomics data integration, protein expression data
MeSH terms
Computer Simulation, Humans, Models, Biological, Proteome, Databases, Protein, Metabolome

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