Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism.

Content Provider	Europe PMC
Author	Jerby, Livnat Shlomi, Tomer Ruppin, Eytan
Copyright Year	2010
Abstract	The computational study of human metabolism has been advanced with the advent of the first generic (non-tissue specific) stoichiometric model of human metabolism. In this study, we present a new algorithm for rapid reconstruction of tissue-specific genome-scale models of human metabolism. The algorithm generates a tissue-specific model from the generic human model by integrating a variety of tissue-specific molecular data sources, including literature-based knowledge, transcriptomic, proteomic, metabolomic and phenotypic data. Applying the algorithm, we constructed the first genome-scale stoichiometric model of hepatic metabolism. The model is verified using standard cross-validation procedures, and through its ability to carry out hepatic metabolic functions. The model's flux predictions correlate with flux measurements across a variety of hormonal and dietary conditions, and improve upon the predictive performance obtained using the original, generic human model (prediction accuracy of 0.67 versus 0.46). Finally, the model better predicts biomarker changes in genetic metabolic disorders than the generic human model (accuracy of 0.67 versus 0.59). The approach presented can be used to construct other human tissue-specific models, and be applied to other organisms.
Journal	Molecular Systems Biology
Volume Number	6
PubMed Central reference number	PMC2964116
PubMed reference number	20823844
e-ISSN	17444292
DOI	10.1038/msb.2010.56
Language	English
Publisher	European Molecular Biology Organization
Publisher Date	2010-09-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. Copyright © 2010, EMBO and Macmillan Publishers Limited
Subject Keyword	constraint based hepatic liver metabolism
Content Type	Text
Resource Type	Article
Subject	Applied Mathematics Computational Theory and Mathematics Information Systems Medicine Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Agricultural and Biological Sciences