Many biological networks tend to have a high modularity structural property and the dynamic characteristic of high robustness against perturbations. However, the relationship between modularity and robustness is not well understood. To investigate this relationship, we examined real signalling networks and conducted simulations using a random Boolean network model. As a result, we first observed that the network robustness is negatively correlated with the network modularity. In particular, this negative correlation becomes more apparent as the network density becomes sparser. Even more interesting is that, the negative relationship between the network robustness and the network modularity occurs mainly because nodes in the same module with the perturbed node tend to be more sensitive to the perturbation than those in other modules. This result implies that dynamically similar nodes tend to be located in the same module of a network. To support this, we show that a pair of genes associated with the same disease or a pair of functionally similar genes is likely to belong to the same module in a human signalling network.
Specific molecular signaling networks underlie different cancer types and quantitative analyses on those cancer networks can provide useful information about cancer treatments. Their structural metrics can reveal survivability of cancer patients and be used to identify biomarker genes for early cancer detection. In this study, we devised a novel structural metric called hierarchical closeness (HC) entropy and found that it was negatively correlated with 5-year survival rates. We also made an interesting observation that a network of higher HC entropy was likely to be more robust against mutations. This finding suggested that cancers of high HC entropy tend to be incurable because their signaling networks are robust to perturbations caused by treatment. We also proposed a novel core identification method based on the reachability factor in the HC measure. The cores were permitted to decompose such that the negative relationship between HC entropy and cancer survival rate was consistently conserved in every core level. Interestingly, we observed that many promising biomarker genes for early cancer detection reside in the innermost core of a signaling network. Taken together, the proposed analyses of the hierarchical structure of cancer signaling networks may be useful in developing future novel cancer treatments.
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