Disclosed herein is a systems biology approach to prediction of phenotypically relevant genes such as oncogenes and perturbation targets. Interactions from a comprehensive cellular network such as the B Cell Interactome (BCI) can be used to identify those that become affected, or dysregulated, by a phenotype (e.g, disease, tumor and cancer) or perturbation (e.g., drug treatment) based on correlation changes between expression profiles of gene pairs in the interactions upon removal or addition of samples showing the phenotype or perturbation. Genes can be ranked based on the affected interactions involving the genes to predict phenotypically relevant genes and/or perturbation targets.