title: Large-scale in silico modeling of metabolic interactions between cell types in the human brain.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schramm
authors.forename: Aarash
authors.initials: A
authors.lastname: Bordbar
authors.forename: Jan
authors.initials: J
authors.lastname: Schellenberger
authors.forename: Michael P
authors.initials: MP
authors.lastname: Andersen
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Cheng
authors.forename: Nilam
authors.initials: N
authors.lastname: Patel
authors.forename: Alex
authors.initials: A
authors.lastname: Yee
authors.forename: Randall A
authors.initials: RA
authors.lastname: Lewis
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Rainer
authors.initials: R
authors.lastname: König
authors.forename: Bernhard Ø
authors.initials: BØ
authors.lastname: Palsson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D003198:Computer Simulation; D016208:Databases, Factual; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D010641:Phenotype
chemical_list: D000109:Acetylcholine