Mardinoglu2014 - Genome-scale metabolic model (HMR version 2.0) - human hepatocytes (iHepatocytes2322)

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Mardinoglu2014 - Genome-scale metabolic model (HMR version 2.0) - human hepatocytes (iHepatocytes2322)

This model is described in the article:

Mardinoglu A, Agren R, Kampf C, Asplund A, Uhlen M, Nielsen J.
Nat Commun 2014; 5: 3083

Abstract:

Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis.

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Format
SBML (L2V3)
Related Publication
  • Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease.
  • Mardinoglu A, Agren R, Kampf C, Asplund A, Uhlen M, Nielsen J
  • Nature communications , 0/ 2014 , Volume 5 , pages: 3083
  • 1] Department of Chemical and Biological Engineering, Chalmers University of Technology, Kamivangen 10, Gothenburg SE-412 96, Sweden [2].
  • Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis.
Contributors
Varun Kothamachu, Adil Mardinoglu

Metadata information

is
BioModels Database MODEL1402200003
Taxonomy Homo sapiens
isVersionOf
occursIn
Brenda Tissue Ontology hepatocyte
Curation status
Non-curated
Original model(s)
Human Metabolic Reaction (HMR) 2.0 Database
  • Model originally submitted by : Varun Kothamachu
  • Submitted: 20-Feb-2014 10:37:23
  • Last Modified: 18-Aug-2017 16:14:56
Revisions
  • Version: 3 public model Download this version
    • Submitted on: 18-Aug-2017 16:14:56
    • Submitted by: Varun Kothamachu
    • With comment: Notes updated using online editor.
  • Version: 2 public model Download this version
    • Submitted on: 21-Feb-2014 12:27:09
    • Submitted by: Adil Mardinoglu
    • With comment: Current version of Mardinoglu2014 - Genome-scale metabolic model (HMR verson 2.0) - human hepatocytes (iHepatocytes2322)
  • Version: 1 public model Download this version
    • Submitted on: 20-Feb-2014 10:37:23
    • Submitted by: Adil Mardinoglu
    • With comment: Original import of MODEL1402200003.xml.origin