Updated in 12/17/2010 3:53:28 AM      Viewed: 65 times      (Journal Article)
Nature biotechnology 28 (12): 1279-85 (2010)

Large-scale in silico modeling of metabolic interactions between cell types in the human brain.

Nathan E Lewis , Gunnar Schramm , Aarash Bordbar , Jan Schellenberger , Michael P Andersen , Jeffrey K Cheng , Nilam Patel , Alex Yee , Randall A Lewis , Roland Eils , Rainer König , Bernhard Ø Palsson
Metabolic interactions between multiple cell types are difficult to model using existing approaches. Here we present a workflow that integrates gene expression data, proteomics data and literature-based manual curation to model human metabolism within and between different types of cells. Transport reactions are used to account for the transfer of metabolites between models of different cell types via the interstitial fluid. We apply the method to create models of brain energy metabolism that recapitulate metabolic interactions between astrocytes and various neuron types relevant to Alzheimer's disease. Analysis of the models identifies genes and pathways that may explain observed experimental phenomena, including the differential effects of the disease on cell types and regions of the brain. Constraint-based modeling can thus contribute to the study and analysis of multicellular metabolic processes in the human tissue microenvironment and provide detailed mechanistic insight into high-throughput data analysis.
DOI: 10.1038/nbt.1711      ISSN: 1087-0156