Subnetwork signatures of CLL disease progression. (A) Activity of the 38 significant subnetworks (rows) across the 130 patients (columns). The color of each block scales with the activity level of a subnetwork in a particular patient. Patients are clustered into high/low-risk groups, and subnetworks are clustered into 3 functional categories (proliferation and death, signaling, and metabolism). Blue bars above the heatmap show the intervals of SC→TX for each sample while green bars chart the intervals of DX→TX. (B) Kaplan-Meier analysis yields treatment-free probabilities with regard to the 3 risk groups defined by subnetwork activity patterns. (C) Distribution of the predominant cellular functions associated with the 38 subnetworks. Related functions are clustered into categories named on the outer circle. The marked functions in the inner circle are associated with at least 2% of the subnetworks. See supplemental Figure 4 for all enriched functions. (D) Top enriched signaling cascades. Bars show numbers of the 38 subnetworks, which have member genes involved in each pathway. (E) Comparison of patient stratification by subnetwork prognosis versus IGHV mutation status.