ToppGeNet differs from ToppGene and ToppNet in that the test set is derived from the protein interactome. In other words, for a training set of known disease genes, the test set is generated by mining the protein interactome and compiling the genes either directly or indirectly interacting (based on user input) with the training set. After any overlapping or common genes between test and training sets are removed, interactome-based test set genes can be prioritized using either a functional annotation-based method (ToppGene) or PPIN-based method (ToppNet). The human protein interaction dataset (file ‘interactions.gz’), a compilation of PPIs from BIND (32), BioGRID (33) and HPRD (34), is downloaded from NCBI Entrez Gene FTP site (ftp://ftp.ncbi.nih.gov/gene/).