Recon 2.2: from reconstruction to model of human metabolism
Autor: | Pedro Mendes, Dong-Yup Lee, Michael Hanscho, Nathan E. Lewis, Douglas B. Kell, Meiyappan Lakshmanan, Jahir M. Gutierrez, Alex Thomas, Natalie J. Gardiner, Joanne K. Liu, Shangzhong Li, Paul D. Dobson, Juergen Zanghellini, Hooman Hefzi, Kok Siong Ang, Camila A. Orellana, Veronica Martinez, Neil Swainston, Nicole Borth, Lars K. Nielsen, Daniel C. Zielinski, Kieran Smallbone, Sarantos Kyriakopoulos, Judy Brewer, Lake-Ee Quek |
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Přispěvatelé: | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Brewer, Judith A |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Short Communication Endocrinology Diabetes and Metabolism Systems biology Clinical Sciences Clinical Biochemistry Human metabolism Computational biology Biology Bioinformatics Biochemistry Modelling Analytical Chemistry Task (project management) 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Manchester Institute of Biotechnology Genetics Nutrition 2. Zero hunger Human Genome ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology Metabolism 030104 developmental biology Generic health relevance Biochemistry and Cell Biology Reconstruction Developmental biology 030217 neurology & neurosurgery Biotechnology Human Model |
Zdroj: | Springer US Metabolomics : Official journal of the Metabolomic Society, vol 12, iss 7 Metabolomics Swainston, N, Smallbone, K, Hefzi, H, Dobson, P D, Brewer, J, Hanscho, M, Zielinski, D C, Ang, K S, Gardiner, N, Gutierrez, J M, Kyriakopoulos, S, Lakshmanan, M, Li, S, Liu, J K, Martínez, V S, Orellana, C A, Quek, L-E, Thomas, A, Zanghellini, J, Borth, N, Lee, D-Y, Nielsen, L K, Kell, D, Lewis, N E & Mendes, P 2016, ' Recon 2.2 : from reconstruction to model of human metabolism ', Metabolomics : Official journal of the Metabolomic Society, vol. 12, pp. 109 . https://doi.org/10.1007/s11306-016-1051-4 Swainston, N, Smallbone, K, Hefzi, H, Dobson, P D, Brewer, J, Hanscho, M, Zielinski, D C, Ang, K S, Gardiner, N J, Gutierrez, J M, Kyriakopoulos, S, Lakshmanan, M, Li, S, Liu, J K, Martínez, V S, Orellana, C A, Quek, L E, Thomas, A, Zanghellini, J, Borth, N, Lee, D Y, Nielsen, L K, Kell, D B, Lewis, N & Mendes, P 2016, ' Recon 2.2 : from reconstruction to model of human metabolism ', Metabolomics, vol. 12, 109 . https://doi.org/10.1007/s11306-016-1051-4 |
ISSN: | 1573-3890 1573-3882 |
Popis: | Introduction 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. Objectives 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. Conclusion 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). Electronic supplementary material The online version of this article (doi:10.1007/s11306-016-1051-4) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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