Schematic representation of workflow and methodology in ToppGene Suite applications. (A) Genes in the training set are selected based on their attributes or current gene annotations (genes associated with a disease, phenotype, pathway or a GO term). (B) The test gene source can be candidate genes from linkage analysis studies or genes differentially expressed in a particular disease or phenotype or genes from the interactome. (C) ToppFunEnriched terms of the gene annotations and sequence features, namely, GO: Molecular Function, GO: Biological Process, Mouse Phenotype, Pathways, Protein Interactions, Protein Domains, transcription factor-binding sites, miRNA-target genes, disease-gene associations, drug-gene interactions, and Gene Expression, compiled from various data sources and also used to build the training set gene profile. (C and D) ToppGene—a similarity score is generated for each annotation of each test gene by comparing to the enriched terms in the training set of genes. The final prioritized gene list is then computed based on the aggregated values of the 14 similarity scores. (E and F) ToppNet—Training and test set genes are mapped to a protein–protein interaction network. Scoring and ranking of test set genes are based on the relative location to all of the training set genes using global network-distance measures in the PPIN.