Evidence map›Paper›PMID 27358602›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society

Recon 2.2: from reconstruction to model of human metabolism.

Neil Swainston, Kieran Smallbone, Hooman Hefzi, Paul D Dobson, Judy Brewer, Michael Hanscho, Daniel C Zielinski, Kok Siong Ang, Natalie J Gardiner, Jahir M Gutierrez and 15 more

Open access · hybridAbstract read
In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed
22.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

152 citing papers in PubMed, 328 citations in OpenAlex.

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  11. Simulated metabolic profiles reveal biases in pathway analysis methods.Metabolomics : Official journal of the Metabolomic Society · 2025
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  12. Longitudinal big biological data in the AI era.Molecular systems biology · 2025
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  18. Genome-scale models in human metabologenomics.Nature reviews. Genetics · 2025
    Review
  19. Review
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92 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 11 institutions in 5 countries.

Neil SwainstonManchester 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.
Kieran SmallboneSchool of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
Hooman HefziDepartment 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.
Paul D DobsonSchool of Computer Science, The University of Manchester, Manchester, M13 9PL UK.
Judy BrewerHarvard 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.
Michael HanschoDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Daniel C ZielinskiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA USA.
Kok Siong AngDepartment 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.
Natalie J GardinerFaculty of Life Sciences, The University of Manchester, Manchester, M13 9PL UK.
Jahir M GutierrezDepartment 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.
Sarantos KyriakopoulosBioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
Meiyappan LakshmananBioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore, 138668 Singapore.
Shangzhong LiDepartment 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.
Joanne K LiuBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA USA.
Veronica S MartínezAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
Camila A OrellanaAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
Lake-Ee QuekAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
Alex ThomasNovo 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.
Juergen ZanghelliniAustrian Centre of Industrial Biotechnology, Vienna, Austria.
Nicole BorthDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Dong-Yup LeeDepartment 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.
Lars K NielsenAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072 Australia.
Douglas B KellManchester 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.
Nathan E LewisNovo 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.
Pedro MendesManchester 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.
University of Manchester · GBUniversity of California, San Diego · USUniversity of Queensland · AUBOKU University · ATFoundation Center · USNational University of Singapore · SGAgency for Science, Technology and Research · SGAustrian Centre of Industrial Biotechnology (Austria) · ATBioprocessing Technology Institute · SGLa Jolla Bioengineering Institute · USUConn Health · US

Funding

COPASI software for modeling and simulation of biochemical networksR01GM080219 · NIGMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI HOOPS, STEFAN, MENDES, PEDRO · 2007 to 2019
$5.4M
Biotechnology and Biological Sciences Research Council BB/K019783/1Biotechnology and Biological Sciences Research Council BB/M017702/1NIGMS NIH HHS R01 GM080219
6 · The paper itself

Abstract

introductionThe 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.

objectivesWe 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.

methodsRecon 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.

resultsRecon 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.

conclusionThrough 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).

Indexed as

HumanMetabolismModelModellingReconstructionSystems biology

Identifiers

PMID27358602
PMCPMC4896983
OpenAlexW2418056440

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.