Figure 1

Overview of analysis procedure. (A) Flow chart of the analysis pipeline. (B) Schematic illustration of the concept of second-order similarity. It is obvious that the overall expression similarity between the two gene pairs (genes 1 and 2 versus genes 3 and 4) is not significantly high, but their first-order expression correlation profiles exhibit high second-order similarity. (C) Schematic illustration of the dissection of differential co-expression networks into network modules based on the co-expression dynamics and network connectivity. In the heat map, every column corresponds to a dataset and every row corresponds to a gene pair. Red, black, green and grey corresponds to positive, low, negative and missing correlations, respectively. By hierarchical clustering, the gene pairs fall into two major second-order clusters. The 9 gene pairs in the green cluster comprise three connected network components, whereas the 6 gene pairs in the red cluster give rise to three connected components. Furthermore, by considering the second order cluster of a higher level of the hierarchy, which consists of both green and red clusters, the six networks are united to form two connected networks, reflecting the hierarchical modularity of cancer co-expression networks.