A community-driven global reconstruction of human metabolism

被引：697

作者：

Thiele, Ines ^{[1
,2
]}

Swainston, Neil ^{[3
,4
]}

Fleming, Ronan M. T. ^{[1
,5
]}

Hoppe, Andreas ^{[6
]}

Sahoo, Swagatika ^{[1
]}

Aurich, Maike K. ^{[1
]}

Haraldsdottir, Hulda ^{[1
]}

Mo, Monica L. ^{[7
]}

Rolfsson, Ottar ^{[1
]}

Stobbe, Miranda D. ^{[8
,9
]}

Thorleifsson, Stefan G. ^{[1
]}

Agren, Rasmus ^{[10
]}

Boelling, Christian ^{[6
]}

Bordel, Sergio ^{[10
]}

Chavali, Arvind K. ^{[11
]}

Dobson, Paul ^{[12
]}

Dunn, Warwick B. ^{[3
,13
]}

Endler, Lukas ^{[14
]}

Hala, David ^{[15
]}

Hucka, Michael ^{[16
]}

Hull, Duncan ^{[4
]}

Jameson, Daniel ^{[3
,4
]}

Jamshidi, Neema ^{[7
]}

Jonsson, Jon J. ^{[5
]}

Juty, Nick ^{[17
]}

Keating, Sarah ^{[17
]}

Nookaew, Intawat ^{[10
]}

Le Novere, Nicolas ^{[17
,18
]}

Malys, Naglis ^{[3
,19
,20
]}

Mazein, Alexander ^{[21
]}

Papin, Jason A. ^{[11
]}

Price, Nathan D. ^{[22
]}

Selkov, Evgeni, Sr. ^{[23
]}

Sigurdsson, Martin I. ^{[1
]}

Simeonidis, Evangelos ^{[22
,24
]}

Sonnenschein, Nikolaus ^{[25
]}

Smallbone, Kieran ^{[3
,26
]}

Sorokin, Anatoly ^{[21
,27
]}

van Beek, Johannes H. G. M. ^{[28
,29
,30
]}

Weichart, Dieter ^{[3
,31
]}

Goryanin, Igor ^{[21
,32
]}

Nielsen, Jens ^{[10
]}

Westerhoff, Hans V. ^{[28
,33
,34
]}

Kell, Douglas B. ^{[35
]}

Mendes, Pedro ^{[36
]}

Palsson, Bernhard O.

机构：

[1] Univ Iceland, Ctr Syst Biol, Reykjavik, Iceland

[2] Univ Iceland, Fac Ind Engn Mech Engn & Comp Sci, Reykjavik, Iceland

[3] Univ Manchester, Manchester Inst Biotechnol, Manchester Ctr Integrat Syst Biol, Manchester, Lancs, England

[4] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England

[5] Univ Iceland, Dept Biochem & Mol Biol, Reykjavik, Iceland

[6] Charite, Computat Syst Biochem Grp, D-13353 Berlin, Germany

[7] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[8] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinform, NL-1105 AZ Amsterdam, Netherlands

[9] Netherlands Bioinformat Ctr, Nijmegen, Netherlands

[10] Chalmers Univ Technol, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden

[11] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA

[12] Univ Sheffield, Dept Chem & Biol Engn, Sheffield, S Yorkshire, England

[13] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, CADET, Manchester, Lancs, England

[14] Univ Vienna, Inst Theoret Chem, Vienna, Austria

[15] Univ N Texas, Dept Biol, Denton, TX 76203 USA

[16] CALTECH, Comp & Math Sci Dept, Pasadena, CA 91125 USA

[17] European Bioinformat Inst, European Mol Biol Lab, Hinxton, England

[18] Babraham Inst, Cambridge, England

[19] Univ Manchester, Fac Life Sci, Manchester, Lancs, England

[20] Univ Warwick, Sch Life Sci, Coventry CV4 7AL, W Midlands, England

[21] Univ Edinburgh, Sch Informat, Edinburgh, Midlothian, Scotland

[22] Inst Syst Biol, Seattle, WA USA

[23] Genome Designs Inc, Walnut Creek, CA USA

[24] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg

[25] Univ Bremen, Sch Sci & Engn, D-28359 Bremen, Germany

[26] Univ Manchester, Sch Math, Manchester, Lancs, England

[27] Russian Acad Sci, Inst Cell Biophys, Pushchino 142292, Moscow Region, Russia

[28] Vrije Univ Amsterdam, Dept Mol Cell Physiol, Amsterdam, Netherlands

[29] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Sect Med Gen, Amsterdam, Netherlands

[30] Netherlands Consortium Syst Biol, Amsterdam, Netherlands

[31] Univ Manchester, Sch Dent, Manchester, Lancs, England

[32] Okinawa Inst Sci & Technol, Okinawa, Japan

[33] Univ Manchester, Sch Chem Engn & Analyt Sci, Manchester, Lancs, England

[34] Univ Amsterdam, Fac Sci, Swammerdam Inst Life Sci, Amsterdam, Netherlands

[35] Univ Manchester, Sch Chem, Manchester, Lancs, England

[36] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA

来源：

NATURE BIOTECHNOLOGY | 2013年 / 31卷 / 05期

基金：

英国工程与自然科学研究理事会; 美国国家科学基金会; 英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 欧洲研究理事会; 英国科学技术设施理事会;

关键词：

SYSTEMS BIOLOGY; INBORN-ERRORS; NETWORK; MODELS; KNOWLEDGEBASE; ANNOTATION; PREDICTION; CANCER; SBML;

D O I：

10.1038/nbt.2488

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 similar to 2x more reactions and similar to 1.7x 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/.

引用

页码：419 / +

页数：9

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