Schematic overview of subnetwork identification and definition of risk groups. (A) The expression profile of each gene is projected onto its corresponding protein in a protein-protein interaction subnetwork. A greedy search is performed to find subnetworks for which the activities are associated with the time from sample collection to treatment (SC→TX). Significant subnetworks are selected based on null distributions estimated from permuted data. Subnetworks are used to identify disease genes, and the subnetwork activity is used to characterize the signatures of different risk groups. (B) K-means clustering segregates patients by their distinct subnetwork activity patterns. (C) Patient clusters are assigned high versus low risk based on median treatment-free probabilities in a Kaplan-Meier analysis.