A community-driven global reconstruction of human metabolism
Ines Thiele,Neil Swainston,Ronan M. T. Fleming,Andreas Hoppe,Swagatika Sahoo,Maike K. Aurich,Hulda S. Haraldsdóttir,Monica L. Mo,Ottar Rolfsson,Miranda D. Stobbe,Miranda D. Stobbe,Stefan Gretar Thorleifsson,Rasmus Agren,Christian Bölling,Sergio Bordel,Arvind K. Chavali,Paul D. Dobson,Warwick B. Dunn,Warwick B. Dunn,Lukas Endler,David Hala,Michael Hucka,Duncan Hull,Daniel Jameson,Neema Jamshidi,Jon J. Jonsson,Nick Juty,Sarah M. Keating,Intawat Nookaew,Nicolas Le Novère,Nicolas Le Novère,Naglis Malys,Naglis Malys,Alexander Mazein,Jason A. Papin,Nathan D. Price,Evgeni Selkov,Martin I. Sigurdsson,Evangelos Simeonidis,Evangelos Simeonidis,Nikolaus Sonnenschein,Kieran Smallbone,Anatoly Sorokin,Anatoly Sorokin,Johannes H. G. M. van Beek,Dieter Weichart,Igor Goryanin,Jens Nielsen,Hans V. Westerhoff,Douglas B. Kell,Pedro Mendes,Pedro Mendes,Bernhard O. Palsson,Bernhard O. Palsson +53 more
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Recon 2, a community-driven, consensus 'metabolic reconstruction', is described, which is the most comprehensive representation of human metabolism that is applicable to computational modeling and has improved topological and functional features.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/.read more
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Book ChapterDOI
Deducing intracellular distributions of metabolic pathways from genomic data
Ansgar Gruber,Peter G. Kroth +1 more
TL;DR: This chapter presents procedures and approaches to identify and characterize gene models of enzymes involved in metabolic pathways based on their similarity to known sequences and describes how to predict the subcellular location of the proteins using publicly available prediction servers and how to interpret the obtained results.
Journal ArticleDOI
Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig
Nathalie Poupin,Marie Tremblay-Franco,Aurélien Amiel,Cécile Canlet,Didier Rémond,Laurent Debrauwer,Dominique Dardevet,Ines Thiele,Maike K. Aurich,Fabien Jourdan,Isabelle Savary-Auzeloux,Sergio Polakof +11 more
TL;DR: The unique combination of experimental data and modelling predictions suggested that HFHS feeding was associated with changes in tryptophan metabolism and fatty acid β-oxidation, which may play an important role in lipid hepatic accumulation and insulin sensitivity.
Posted ContentDOI
A comprehensive, mechanistically detailed, and executable model of the Cell Division Cycle in Saccharomyces cerevisiae
TL;DR: A comprehensive mechanistic model of the molecular network that controls the cell division cycle in Saccharomyces cerevisiae is presented, using rxncon, the reaction-contingency language, to neutralise the scalability issues preventing formulation, visualisation and simulation of signalling networks at the genome-scale.
Journal ArticleDOI
Computational approaches for understanding energy metabolism.
TL;DR: Several approaches used to quantitatively model metabolic pathways relating to energy metabolism and discuss their formalisms, successes, and limitations are discussed in this paper, with a focus on energy metabolism.
Posted ContentDOI
In Silico Modeling of Metabolic State in Single Th17 Cells Reveals Novel Regulators of Inflammation and Autoimmunity
Allon Wagner,Chao Wang,Chao Wang,David DeTomaso,Julian Avila-Pacheco,Sarah Zaghouani,Johannes Fessler,Sequoia Eyzaguirre,Elliot Akama-Garren,Kerry A. Pierce,Noga Ron-Harel,Vivian Paraskevi Douglas,Marcia C. Haigis,Raymond A. Sobel,Clary B. Clish,Aviv Regev,Aviv Regev,Vijay K. Kuchroo,Vijay K. Kuchroo,Nir Yosef +19 more
TL;DR: In this paper, a single-cell RNA-Seq and flux balance analysis was applied to associate metabolic states with functional variability (pathogenic potential) amongst Th17 cells and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known differences between Th17 and Treg cells, as well as novel targets in amino acid pathways.
References
More filters
Journal ArticleDOI
What is flux balance analysis
TL;DR: This primer covers the theoretical basis of the approach, several practical examples and a software toolbox for performing the calculations.
Journal ArticleDOI
The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.
Michael Hucka,Andrew Finney,Herbert M. Sauro,Hamid Bolouri,Hamid Bolouri,John Doyle,Hiroaki Kitano,Adam P. Arkin,Benjamin Bornstein,Dennis Bray,Athel Cornish-Bowden,Autumn A. Cuellar,S. Dronov,E. D. Gilles,Martin Ginkel,V. Gor,Igor Goryanin,W. J. Hedley,T. C. Hodgman,J.-H.S. Hofmeyr,Peter Hunter,Nick Juty,J. L. Kasberger,Andreas Kremling,Ursula Kummer,N Le Novère,Leslie M. Loew,D. Lucio,Pedro Mendes,E. Minch,Eric Mjolsness,Yoichi Nakayama,Melanie R. Nelson,Poul M. F. Nielsen,T. Sakurada,James C. Schaff,Bruce E. Shapiro,Thomas S. Shimizu,H. D. Spence,Jörg Stelling,Koichi Takahashi,Masaru Tomita,John Wagner,J. Wang +43 more
TL;DR: This work summarizes the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks, a software-independent language for describing models common to research in many areas of computational biology.
Journal ArticleDOI
DrugBank: a knowledgebase for drugs, drug actions and drug targets
David S. Wishart,Craig Knox,An Chi Guo,Dean Cheng,Savita Shrivastava,Dan Tzur,Bijaya Gautam,Murtaza Hassanali +7 more
TL;DR: The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release and contains 60% more FDA-approved small molecule and biotech drugs including 10% more ‘experimental’ drugs.
Journal ArticleDOI
Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
William R. Wikoff,Andrew T. Anfora,Jun Liu,Peter G. Schultz,Scott A. Lesley,Eric C. Peters,Gary Siuzdak +6 more
TL;DR: A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of theHost.
Journal ArticleDOI
Towards a knowledge-based Human Protein Atlas
Mathias Uhlén,Per Oksvold,Linn Fagerberg,Emma Lundberg,Kalle Jonasson,Mattias Forsberg,Martin Zwahlen,Caroline Kampf,Kenneth Wester,Sophia Hober,Henrik Wernérus,Lisa Björling,Fredrik Pontén +12 more
TL;DR: The analysis here suggests that state stem cell funding programs are sufficiently large and established that simply ending the programs, at least in the absence of substantial investment in the field by other funding sources, could have deleterious effects.