title: Recon 2.2: from reconstruction to model of human metabolism.
abstract: BACKGROUND
  The human genome-scale metabolic reconstruction details all known metabolic reactions occurring in humans, and thereby holds substantial promise for studying complex diseases and phenotypes. Capturing the whole human metabolic reconstruction is an on-going task and since the last community effort generated a consensus reconstruction, several updates have been developed.
  
  
  OBJECTIVE
  We report a new consensus version, Recon 2.2, which integrates various alternative versions with significant additional updates. In addition to re-establishing a consensus reconstruction, further key objectives included providing more comprehensive annotation of metabolites and genes, ensuring full mass and charge balance in all reactions, and developing a model that correctly predicts ATP production on a range of carbon sources.
  
  
  METHODS
  Recon 2.2 has been developed through a combination of manual curation and automated error checking. Specific and significant manual updates include a respecification of fatty acid metabolism, oxidative phosphorylation and a coupling of the electron transport chain to ATP synthase activity. All metabolites have definitive chemical formulae and charges specified, and these are used to ensure full mass and charge reaction balancing through an automated linear programming approach. Additionally, improved integration with transcriptomics and proteomics data has been facilitated with the updated curation of relationships between genes, proteins and reactions.
  
  
  RESULTS
  Recon 2.2 now represents the most predictive model of human metabolism to date as demonstrated here. Extensive manual curation has increased the reconstruction size to 5324 metabolites, 7785 reactions and 1675 associated genes, which now are mapped to a single standard. The focus upon mass and charge balancing of all reactions, along with better representation of energy generation, has produced a flux model that correctly predicts ATP yield on different carbon sources.
  
  
  CONCLUSIONS
  Through these updates we have achieved the most complete and best annotated consensus human metabolic reconstruction available, thereby increasing the ability of this resource to provide novel insights into normal and disease states in human. The model is freely available from the Biomodels database (http://identifiers.org/biomodels.db/MODEL1603150001).
authors.affiliation: Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PL UK ; School of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Swainston
authors.affiliation: School of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Smallbone
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA USA ; Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA USA.
authors.forename: Hooman
authors.initials: H
authors.lastname: Hefzi
authors.affiliation: School of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dobson
authors.affiliation: Harvard Extension School, 51 Brattle St., Cambridge, MA 02138 USA ; Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St., Cambridge, MA 02139 USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Brewer
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanscho
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Zielinski
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585 Singapore ; Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
authors.forename: Kok Siong
authors.initials: KS
authors.lastname: Ang
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PL UK.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Gardiner
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA USA ; Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA USA.
authors.forename: Jahir M
authors.initials: JM
authors.lastname: Gutierrez
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
authors.forename: Sarantos
authors.initials: S
authors.lastname: Kyriakopoulos
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
authors.forename: Meiyappan
authors.initials: M
authors.lastname: Lakshmanan
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA USA ; Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA USA.
authors.forename: Shangzhong
authors.initials: S
authors.lastname: Li
authors.affiliation: Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA USA.
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Liu
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
authors.forename: Veronica S
authors.initials: VS
authors.lastname: Martínez
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
authors.forename: Camila A
authors.initials: CA
authors.lastname: Orellana
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
authors.forename: Lake-Ee
authors.initials: LE
authors.lastname: Quek
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA USA ; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Juergen
authors.initials: J
authors.lastname: Zanghellini
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585 Singapore ; Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
authors.forename: Dong-Yup
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
authors.forename: Lars K
authors.initials: LK
authors.lastname: Nielsen
authors.affiliation: Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; School of Chemistry, The University of Manchester, Manchester, M13 9PL UK.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego School of Medicine, La Jolla, CA USA ; Department of Pediatrics, University of California, San Diego, La Jolla, CA USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.affiliation: Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK ; School of Computer Science, The University of Manchester, Manchester, M13 9PL UK ; Center for Quantitative Medicine, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-6033 USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendes
keywords: Human; Metabolism; Model; Modelling; Reconstruction; Systems biology