NetwoRx: connecting drugs to networks and phenotypes in Saccharomyces cerevisiae

Drug modes of action are complex and still poorly understood. The set of known drug targets is widely acknowledged to be biased and incomplete, and so gives only limited insight into the system-wide effects of drugs. But a high-throughput assay unique to yeast-barcode-based chemogenomic screens-can measure the individual drug response of every yeast deletion mutant in parallel. NetwoRx (http://ophid.utoronto.ca/networx) is the first resource to store data from these extremely valuable yeast chemogenomics experiments. In total, NetwoRx stores data on 5924 genes and 466 drugs. In addition, we applied data-mining approaches to identify yeast pathways, functions and phenotypes that are targeted by particular drugs, compute measures of drug-drug similarity and construct drug-phenotype networks. These data are all available to search or download through NetwoRx; users can search by drug name, gene name or gene set identifier. We also set up automated analysis routines in NetwoRx; users can query new gene sets against the entire collection of drug profiles and retrieve the drugs that target them. We demonstrate with use case examples how NetwoRx can be applied to target specific phenotypes, repurpose drugs using mode of action analysis, investigate bipartite networks and predict new drugs that affect yeast aging.