Quantifying landscape and flux as the global physical driving forces for cancer from low and high throughput experiments

Cancer has been a serious deasease for human health. Genetic mutations have often been thought to be mainly responsible for the cancer formation. More evidence accumuated that cancer emergence is not just caused by individual gene perturbation but also from the whole network or state of the system. This shift of thinking demands global quantification and physical understanding of the underlying mechanisms for cancer formation. Here, we develop cancer models from the underlying gene regulatory networks either based on the available low throughput or the recent high throughput sequence experimental studies. Cancer landscape can be quantified and cancer can be revealed as attractors representing cancer states. The landscape barrier and switching time become the measures of how difficult to transform from normal to cancer state. Furthemore, the cancer formation process can be quantified by the optimal paths between the normal state and cancer state. Due to the presence of the curl flux as the nonequilibrium driving force, the forward path and backward paths for cancer formation and normal state restoration are distinctly different. The global sensitivity analysis based on the landscape topography and nonequilibrium driving forces identify key genes and regulations responsible for the cancer formation. We further identify the nonequilibrium indicators through the curl flux, entropy production and time irreversibility as the early warning signals for the cancer formation. This helps to design practical strategy for cancer prevention and treatment.