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PMID: 23455439 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A community-driven global reconstruction of human metabolism.

Nature biotechnology ·Vol. 31 ·No. 5 ·2013-05-00 ·Pages 419-25

Thiele I, Swainston N, Fleming RM, Hoppe A, Sahoo S, Aurich MK, Haraldsdottir H, Mo ML, Rolfsson O, Stobbe MD, Thorleifsson SG, Agren R, Bölling C, Bordel S, Chavali AK, Dobson P, Dunn WB, Endler L, Hala D, Hucka M, Hull D, Jameson D, Jamshidi N, Jonsson JJ, Juty N, Keating S, Nookaew I, Le Novère N, Malys N, Mazein A, Papin JA, Price ND, Selkov E, Sigurdsson MI, Simeonidis E, Sonnenschein N, Smallbone K, Sorokin A, van Beek JH, Weichart D, Goryanin I, Nielsen J, Westerhoff HV, Kell DB, Mendes P, Palsson BØ

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/.

MeSH Terms
Computer Simulation Databases, Protein Humans Metabolome/physiology Models, Biological Proteome/metabolism
Chemicals
Proteome
Authors & Affiliations
46 authors, click to expand affiliations / ORCID
Thiele Ines
Center for Systems Biology, University of Iceland, Reykjavik, Iceland. [email protected]
Swainston Neil
Fleming Ronan M T
Hoppe Andreas
Sahoo Swagatika
Aurich Maike K
Haraldsdottir Hulda
Mo Monica L
Rolfsson Ottar
Stobbe Miranda D
Thorleifsson Stefan G
Agren Rasmus
Bölling Christian
Bordel Sergio
Chavali Arvind K
Dobson Paul
Dunn Warwick B
Endler Lukas
Hala David
Hucka Michael
Hull Duncan
Jameson Daniel
Jamshidi Neema
Jonsson Jon J
Juty Nick
Keating Sarah
Nookaew Intawat
Le Novère Nicolas
Malys Naglis
Mazein Alexander
Papin Jason A
Price Nathan D
Selkov Evgeni
Sigurdsson Martin I
Simeonidis Evangelos
Sonnenschein Nikolaus
Smallbone Kieran
Sorokin Anatoly
van Beek Johannes H G M
Weichart Dieter
Goryanin Igor
Nielsen Jens
Westerhoff Hans V
Kell Douglas B
Mendes Pedro
Palsson Bernhard Ø
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Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.2488
Email
[email protected]
Published
2013-05-00
Epub
2013-00-03
Pages
419-25
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC3856361
Subset
IM
Grants
NIGMS NIH HHS · R01 GM070923 · United States
Biotechnology and Biological Sciences Research Council · BB/F00561X · United Kingdom
NIGMS NIH HHS · R01 GM088244 · United States
Biotechnology and Biological Sciences Research Council · BBS/E/B/000C0419 · United Kingdom
NIGMS NIH HHS · R01GM080219 · United States
NIGMS NIH HHS · R01 GM080219 · United States
NIGMS NIH HHS · R01GM070923 · United States
Biotechnology and Biological Sciences Research Council · BB/F005938 · United Kingdom
NIGMS NIH HHS · U01 GM102098 · United States
Biotechnology and Biological Sciences Research Council · BB/C008219/1 · United Kingdom
NIGMS NIH HHS · GM088244 · United States
Biotechnology and Biological Sciences Research Council · BB/E006248/1 · United Kingdom
External Links
PubMed source DOI: 10.1038/nbt.2488 PMC Full Text View journal details
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