Investigation on changes of modularity and robustness by edge-removal mutations in signaling networks

Biological networks consisting of molecular components and interactions are represented by a graph model. There have been some studies based on that model to analyze a relationship between structural characteristics and dynamical behaviors in signaling network. However, little attention has been paid to changes of modularity and robustness in mutant networks.

In this paper, we investigated the changes of modularity and robustness by edge-removal mutations in three signaling networks. We first observed that both the modularity and robustness increased on average in the mutant network by the edge-removal mutations. However, the modularity change was negatively correlated with the robustness change. This implies that it is unlikely that both the modularity and the robustness values simultaneously increase by the edge-removal mutations. Another interesting finding is that the modularity change was positively correlated with the degree, the number of feedback loops, and the edge betweenness of the removed edges whereas the robustness change was negatively correlated with them. We note that these results were consistently observed in randomly structure networks. Additionally, we identified two groups of genes which are incident to the highly-modularity-increasing and the highly-robustness-decreasing edges with respect to the edge-removal mutations, respectively, and observed that they are likely to be central by forming a connected component of a considerably large size. The gene-ontology enrichment of each of these gene groups was significantly different from the rest of genes. Finally, we showed that the highly-robustness-decreasing edges can be promising edgetic drug-targets, which validates the usefulness of our analysis.

Taken together, the analysis of changes of robustness and modularity against edge-removal mutations can be useful to unravel novel dynamical characteristics underlying in signaling networks.