Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Syst Biol. 2010 Sep 7;6:401. doi: 10.1038/msb.2010.56.

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

Author information

  • 1The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel. livnatje@post.tau.ac.il

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.

PMID:
20823844
[PubMed - indexed for MEDLINE]
PMCID:
PMC2964116
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk