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Lookup NU author(s): Dr Diego Miranda Saavedra
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.
Author(s): Banerji CRS, Miranda-Saavedra D, Severini S, Widschwendter M, Enver T, Zhou JX, Teschendorff AE
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2013
Volume: 3
Online publication date: 24/10/2013
Acceptance date: 08/10/2013
Date deposited: 13/11/2015
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/srep03039
DOI: 10.1038/srep03039
PubMed id: 24154593
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