Network-basedmethods for human disease gene prediction

Despite the considerable progress in disease gene discovery, we are far from uncovering the underlying cellular mechanisms of diseases since complex traits, even many Mendelian diseases, cannot be explained by simple genotype^phenotype relationships. More recently, an increasingly accepted view is that human diseases result from perturbations of cellular systems, especially molecular networks. Genes associated with the same or similar diseases commonly reside in the same neighborhood of molecular networks. Such observations have built the basis for a large collection of computational approaches to find previously unknown genes associated with certain diseases. The majority of the methods are based on protein interactome networks, with integration of other large-scale genomic data or disease phenotype information, to infer how likely it is that a gene is associated with a disease. Here, we review recent, state of the art, network-based methods used for prioritizing disease genes as well as unraveling the molecular basis of human diseases.