title: Comparing signaling networks between normal and transformed hepatocytes using discrete logical models.
abstract: Substantial effort in recent years has been devoted to constructing and analyzing large-scale gene and protein networks on the basis of "omic" data and literature mining. These interaction graphs provide valuable insight into the topologies of complex biological networks but are rarely context specific and cannot be used to predict the responses of cell signaling proteins to specific ligands or drugs. Conversely, traditional approaches to analyzing cell signaling are narrow in scope and cannot easily make use of network-level data. Here, we combine network analysis and functional experimentation by using a hybrid approach in which graphs are converted into simple mathematical models that can be trained against biochemical data. Specifically, we created Boolean logic models of immediate-early signaling in liver cells by training a literature-based prior knowledge network against biochemical data obtained from primary human hepatocytes and 4 hepatocellular carcinoma cell lines exposed to combinations of cytokines and small-molecule kinase inhibitors. Distinct families of models were recovered for each cell type, and these families clustered topologically into normal and diseased sets.
authors: Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors: Julio
authors: J
authors: Saez-Rodriguez
authors: Leonidas G
authors: LG
authors: Alexopoulos
authors: Mingsheng
authors: M
authors: Zhang
authors: Melody K
authors: MK
authors: Morris
authors: Douglas A
authors: DA
authors: Lauffenburger
authors: Peter K
authors: PK
authors: Sorger
mesh_terms: D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction