Common biochemical and topological properties of metabolic genes recurrently dysregulated in tumors

Although tumors exhibit numerous metabolic alterations, it’s unclear if common objectives and constraints underlie diverse metabolic changes. Here we interpret cancer gene expression, copy number variation, and survival data using a computational model, MetOncoFit. MetOncoFit evaluates142 metabolic features that can impact tumor fitness, including enzyme catalytic activity, pathway association, network topological attributes, and reaction flux. Meta-analysis of tumor databases using MetOncoFit revealed that metabolic enzymes with high catalytic activity were frequently up-regulated in many tumors and associated with poor survival. MetOncoFit also identified metabolites that were hot-spots of dysregulation. MetOncoFit illuminates how enzyme activity and metabolic network architecture influences tumorigenesis.