1202.3015 (James West et al.)

On dynamical network entropy in cancer    [PDF]

James West, Ginestra Bianconi, Simone Severini, Andrew Teschendorff

The cellular phenotype is described by a complex network of molecular
interactions. Elucidating network properties that distinguish disease from the
healthy state is therefore of great importance for gaining systems-level
insights into disease mechanisms and ultimately for developing improved
therapies. Recently, statistical mechanical network properties have been
studied in the context of cancer networks, yet it is unclear which properties
best characterise the cancer phenotype. In this work we take a step in this
direction by comparing two different types of molecular entropy in their
ability to discriminate cancer from the normal phenotype. One entropy measure
(flux entropy) is dynamical in the sense that it is derived from a stochastic
process. The second measure (covariance entropy) does not depend on the
interaction network and is thus "static". Using multiple gene expression data
sets of normal and cancer tissue, we demonstrate that flux entropy is a better
discriminator of the cancer phenotype than covariance entropy. Specifically, we
show that local flux entropy is always increased in cancer relative to normal
tissue while the local covariance entropy is not. We show that gene expression
differences between normal and cancer tissue are anticorrelated with local flux
entropy changes, thus providing a systemic link between gene expression changes
and their local information flux dynamics. We also show that genes located in
the intracellular domain demonstrate preferential increases in flux entropy,
while the entropy of genes encoding membrane receptors and secreted factors is
preferentially reduced. Thus, these results elucidate intrinsic network
properties of cancer and support the view that the observed increased
robustness of cancer cells to perturbation and therapy may be due to an
increase in the dynamical network entropy allowing cells to adapt to
extracellular stresses.

View original: http://arxiv.org/abs/1202.3015