Overview of NetPathID. This figure describes steps to discover disrupted pathways across cancers. The aim of the approach is to integrate the copy number data with protein-protein interaction networks to quantify pathway activity for discovering disrupted pathways across cancers. (A) A list of significantly altered genes residing in copy number regions is generated using GISTIC. (B) We initialize activity scores of these genes using their average log2 ratios of amplification or deletion in copy number data, and overlay initial gene activity scores on the protein-protein interaction networks. To fully utilize network topological information, we apply a label propagation algorithm to assign gene activity scores to all the genes in the protein-protein interaction networks (see “Methods” section). (C) Finally, pathway activity scores are computed by average activity scores of member genes in each predefined pathway from prior knowledge (e.g. pathway database or conserved subnetworks in the protein-protein interaction networks cross species). We repeat step (A) and (B) to generate a matrix containing pathway activity scores from multiple cancer types.