title: A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes.
abstract: We describe a thermodynamic-motivated, information theoretic analysis of proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors. GBMs are considered here as prototypes of heterogeneous cancers. That heterogeneity is viewed here as manifesting in different unbalanced biological processes that are associated with thermodynamic-like constraints. The analysis yields a molecular description of a stable steady state that is common across all tumors. It also resolves molecular descriptions of unbalanced processes that are shared by several tumors, such as hyperactivated phosphoprotein signaling networks. Further, it resolves unbalanced processes that provide unique classifiers of tumor subgroups. The results of the theoretical interpretation are compared against those of statistical multivariate methods and are shown to provide a superior level of resolution for identifying unbalanced processes in GBM tumors. The identification of specific constraints for each GBM tumor suggests tumor-specific combination therapies that may reverse this imbalance.
authors.affiliation: NanoSystems Biology Cancer Center, Division of Chemistry, Caltech , Pasadena, California 91125, United States.|Bio-Medical Sciences Department, The Faculty of Dental Medicine, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Nataly
authors.initials: N
authors.lastname: Kravchenko-Balasha
authors.affiliation: Signaling Programme, The Babraham Institute , Cambridge CB22 3AT, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Johnson
authors.affiliation: Department of Biological Engineering, MIT , Cambridge, Massachusetts 02139, United States.
authors.forename: Forest M
authors.initials: FM
authors.lastname: White
authors.affiliation: NanoSystems Biology Cancer Center, Division of Chemistry, Caltech , Pasadena, California 91125, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine and Department of Chemistry and Biochemistry, UCLA , Los Angeles, California 90095, United States.|The Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: R D
authors.initials: RD
authors.lastname: Levine
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D000069439:Dasatinib / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D018740:Genetic Heterogeneity; D005909:Glioblastoma / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D009363:Neoplasm Proteins; D010750:Phosphoproteins; D000068877:Imatinib Mesylate; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000069439:Dasatinib