NetwoRx: connecting drugs to networks and phenotypes in Saccharomyces cerevisiae

Abstract

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.

Experimental and Computational Analysis of a Large Protein Network That Controls Fat Storage Reveals the Design Principles of a Signaling Network

“…The approach of adding drugs to single mutants to block multiple nodes was chosen in order to avoid the slow growth or lethality frequently observed for double mutants (see [ 55 ]), as well as the necessity to construct all possible double mutants. The chemogenomic approach has often been employed in the yeast system to map synergistic and antagonistic relationships between drug targets and other genes (for recent reviews see [ 56 , 57 ]).…”

Aspergillus Secondary Metabolite Database, a resource to understand the Secondary metabolome of Aspergillus genus

“…AntiSMASH 45 and SMURF 46 are web applications that predict bacterial and fungal secondary metabolic gene clusters 45 . Databases like YEASTRACT 47 , PomBase 48 , NetwoRx 49 are specific to Saccharomyces species, but not to secondary metabolite/metabolism information. ‘ Aspergillus and Aspergillosis’ resource provides secondary metabolite information from Aspergillus species, but redundancy exists and sources remain undefined with major focus on aspergillosis 50 and is currently merged with Central Aspergillus Data REpository (CADRE) 51 .…”

Genomic tools to profile antibiotic mode of action

“…The potential for the amount of biological information discerned from these high-throughput functional studies is promising and will likely have a tremendous impact on the field of antimicrobial drug discovery. Importantly, a robust resource for storing and mining chemical genomics data like the recently developed NetwoRx (Fortney et al, 2013) for yeast chemical genomic screens is undoubtedly needed for bacterial pathogens.…”