A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes
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Author(s) • • • •
Kravchenko-Balasha, Nataly
Johnson, Hannah
Heath, James R.
Levine, R. D.
White, Forest M
Date Issued
July 2016
Journal
Journal of Physical Chemistry B
Publisher
American Chemical Society (ACS)
Citation
Kravchenko-Balasha, Nataly; Johnson, Hannah and White, Forest M. “A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes.” The Journal of Physical Chemistry B 120, 26 (July 2016): 5990–5997 © 2016 American Chemical Society
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1021/acs.jpcb.6b01692