An efficient and effective method to identify significantly perturbed subnetworks in cancer

The identification of key functional biological networks from high-dimensional genomics data is pivotal for cancer research. Here, we introduce FDRnet, a method for the detection of molecular subnetworks in cancer, which addresses several challenges in pathway analysis. FDRnet detects key subnetworks by solving a mixed-integer linear programming problem, using a given upper bound of false discovery rate (FDR) as a budget constraint, and minimizing a conductance score to find dense subgraphs around seed genes. A large-scale benchmark study was performed on both simulation and cancer genomics data. FDRnet outperformed other methods in the ability to detect functionally homogeneous subnetworks in a scale-free biological network, to control FDRs of the genes in detected subnetworks, to improve computational efficiency and to integrate multi-omics data. By overcoming the limitations of existing approaches, FDRnet can facilitate the detection of key functional pathways in cancer and other genetic diseases. The FDRnet method addresses several issues in cancer pathway analysis, including those related to detecting functionally homogeneous subnetworks, controlling the false discovery rate of the genes and handling the computational complexity.